Showing papers in "Toxicology reports in 2015"
TL;DR: The iron chelators showed a concentration dependent increase in their radical scavenging activities as well as their reducing ability, and with the exception of BHA, showed good reducing ability than vitamin C.
Abstract: Inside the human body, reactive derivatives of oxygen, known as reactive oxygen species (ROS) such as the superoxide radical (O2 ), hydroxyl radical ( OH) and hydrogen peroxide (H2O2), are constantly generated. The ROS easily cause oxidative damage to various biomolecules such as proteins, lipids and DNA leading to various disease conditions. Iron chelators function as antioxidants by scavenging ROS and also reduce the amount of available iron thereby decreasing the quantity of OH generated by Fenton reactions. In this study, the antioxidant activity of the iron chelators: caffeic acid (CA), 2,3-dihydroxybenzoic acid (DHBA), desferroxamine B (FOB) and benzohydroxamic acid (BHA) were determined using five different in vitro antioxidant assays. The antioxidant assays used were: iron binding ability, reducing ability using the potassium ferricyanide reduction method, 1,1-diphenyl-2-picrylhydrazyl (DPPH) radical scavenging activity, H2O2 scavenging activity and OH scavenging activity. The standard used for the iron binding ability was Na2EDTA whereas vitamin C was used as a standard for the remaining assays. The iron chelators showed a concentration dependent increase in their radical scavenging activities as well as their reducing ability. At the concentration of 1 mM, FOB had the highest iron binding ability of 93.7% whereas DHBA had the lowest iron binding ability of 5.0% compared to the standard Na2EDTA which had 94.8%. The iron chelators, with the exception of BHA, showed good reducing ability than vitamin C. Caffeic acid showed significant DPPH, hydrogen peroxide and hydroxyl radical scavenging activities of 84.7%, 99.8% and 14.5%, respectively. All the iron chelators were observed to show significant activities in all five antioxidant assays.
171 citations
TL;DR: Synthesized nanoparticles were found to be spherical in shape, well dispersed and stable at various pH values, making them suitable for biomedical and environmental applications and significantly decreasing the cytotoxic impact of bare iron oxide nanoparticles.
Abstract: Iron oxide nanoparticles (INPs) have potential biological, biomedical and environmental applications. These applications require surface modification of the iron oxide nanoparticles, which makes it non-toxic, biocompatible, stable and non-agglomerative in natural and biological surroundings. In the present study, iron oxide nanoparticles (INPs) and chitosan oligosaccharide coated iron oxide nanoparticles (CSO-INPs) were synthesized to evaluate the effect of surface coating on the stability and toxicity of nanoparticles. Comparative in vitro cytotoxicity of nanoparticles was evaluated in HeLa (human cervix carcinoma), A549 (human lung carcinoma) and Hek293 (human embryonic kidney) cells by using 3-(4,5-dimethylthiazol-2-yl)-2,5-diphenyltetrazolium bromide (MTT) assay along with flow cytometry study for cell viability, membrane integrity, mitochondrial membrane potential (MMP) and reactive oxygen species (ROS) production. Morphological alteration in nanoparticles treated cells was analyzed by Acridine orange/ethidium bromide double staining and electron microscopy. Synthesized nanoparticles were found to be spherical in shape, well dispersed and stable at various pH values, making them suitable for biomedical and environmental applications. The present study also indicates that the chitosan oligosaccharide coating on iron oxide nanoparticles results in the decrease in cellular damage and moderate ROS production, thereby, significantly decreasing the cytotoxic impact of bare iron oxide nanoparticles.
159 citations
TL;DR: ZnO and TiO2 NPs exerted roughly equal oxidative stress in terms of aforementioned stress markers and were found to generate reactive oxygen species (ROS) concomitant with depletion of glutathione and GST levels and increased SOD, CAT and lipid peroxidation in dose dependent manner.
Abstract: Nanoparticles (NPs) of zinc oxide (ZnO) and titanium dioxide (TiO2) are receiving increasing attention due to their widespread applications. The aim of this study was to evaluate the toxic effect of ZnO and TiO2 NPs at different concentrations (50, 100, 250 and 500 ppm) and compare them with their respective salts using a battery of cytotoxicity, and genotoxicity parameters. To evaluate cytotoxicity, we have used human erythrocytes and for genotoxic studies human lymphocytes have been used as in vitro model species. Concentration dependent hemolytic activity to RBC's was obtained for both NPs. ZnO and TiO2 NPs resulted in 65.2% and 52.5% hemolysis at 250 ppm respectively indicating that both are cytotoxic to human RBCs. Antioxidant enzymes assays were also carried out in their respective hemolysates. Both nanoparticles were found to generate reactive oxygen species (ROS) concomitant with depletion of glutathione and GST levels and increased SOD, CAT and lipid peroxidation in dose dependent manner. ZnO and TiO2 NPs exerted roughly equal oxidative stress in terms of aforementioned stress markers. Genotoxic potential of both the NPs was investigated by in vitro alkaline comet assay. DNA damage induced by the NPs was concentration dependent and was significantly greater than their ionic forms at 250 and 500 ppm concentrations. Moreover, the nanoparticles of ZnO were significantly more genotoxic than those of TiO2 at higher concentrations. The toxicity of these NPs is due to the generation of ROS thereby causing oxidative stress.
141 citations
TL;DR: To assign use-related information to chemicals to help prioritize which will be given more scrutiny relative to human exposure potential, the CPCat database is used for modeling and prioritizing human chemical exposures.
Abstract: Humans are exposed to thousands of chemicals in the workplace, home, and via air, water, food, and soil. A major challenge in estimating chemical exposures is to understand which chemicals are present in these media and microenvironments. Here we describe the Chemical/Product Categories Database (CPCat), a new, publically available (http://actor.epa.gov/cpcat) database of information on chemicals mapped to "use categories" describing the usage or function of the chemical. CPCat was created by combining multiple and diverse sources of data on consumer- and industrial-process based chemical uses from regulatory agencies, manufacturers, and retailers in various countries. The database uses a controlled vocabulary of 833 terms and a novel nomenclature to capture and streamline descriptors of chemical use for 43,596 chemicals from the various sources. Examples of potential applications of CPCat are provided, including identifying chemicals to which children may be exposed and to support prioritization of chemicals for toxicity screening. CPCat is expected to be a valuable resource for regulators, risk assessors, and exposure scientists to identify potential sources of human exposures and exposure pathways, particularly for use in high-throughput chemical exposure assessment.
113 citations
TL;DR: In this paper, the adverse effects of sub-chronic exposure to the N-phenylpyrazole insecticide Fipronil on the liver and kidney of male rats at three concentrations 0.1, 1 and 10 mg/L in drinking water for 45 days were investigated.
Abstract: Fipronil (FPN) is a broad-spectrum N-phenylpyrazole insecticide and has been used in agriculture and public health since the mid-1990s. The present study was designed to investigate the adverse effects of sub-chronic exposure to the FPN on the liver and kidney of male rats at three concentrations 0.1, 1 and 10 mg/L in drinking water for 45 days. Serum aspartate aminotransferases (AST), alanine aminotransferases (ALT), alkaline phosphatase (ALP), and lactate dehydrogenase (LDH) activity and levels of uric acid, creatinine and total protein were significantly increased in FPN-treated rats. Oxidative stress biomarkers such as superoxide dismutase (SOD), catalase (CAT), glutathione peroxidase (GPx), glutathione-S-transferase (GST) and glutathione reduced (GSH) were significantly decreased, while lipid peroxidation (LPO) was significantly increased in treating rats in a concentration dependent manner. FPN caused histopathological alterations in liver and kidney of male rats. From our results, it can be concluded that FPN induced lipid peroxidation, oxidative stress, liver, and kidney injury in rats. These pathophysiological changes in liver and kidney tissues could be due to the toxic effect of FPN that associated with a generation of free radicals.
108 citations
TL;DR: In this article, an attempt has been made to comprehensively address the impact of Microcystin-LR toxicity on testis, which has shown that MC-LR treated mice exhibit oxidative stress in testis through the alteration of antioxidant enzyme activity and also affect the histopathology of male reproductive system.
Abstract: The worldwide occurrence of cyanobacterial blooms due to water eutrophication evokes extreme concerns. These blooms produce cyanotoxins which are hazardous to living organisms. So far among these toxins, Microcystin-LR (MC-LR) is the most toxic and the most frequently encountered toxin produced by the cyanobacteria in the contaminated aquatic environment. Microcystin-LR is a potential carcinogen for animals and humans, and the International Agency for Research on Cancer has classified Microcystin-LR as a possible human carcinogen. After liver, testis has been considered as one of the most important target organs of Microcystin-LR toxicity. Microcystin-LR crosses the blood-testis barrier and interferes with DNA damage repair pathway and also increases expression of the proto-oncogenes, genes involved in the response to DNA damage, cell cycle arrest, and apoptosis in testis. Toxicity of MC-LR disrupts the motility and morphology of sperm and also affects the hormone levels of male reproductive system. MC-LR treated mice exhibit oxidative stress in testis through the alteration of antioxidant enzyme activity and also affect the histopathology of male reproductive system. In the present review, an attempt has been made to comprehensively address the impact of MC-LR toxicity on testis.
105 citations
TL;DR: Data from agglomerated MO NPs suggests that the elemental composition and dissolution potential are major drivers of toxicity, and exposure to dissolved Zn2+ may be a major contributor to ZnO toxicity.
Abstract: Engineered metal oxide nanoparticles (MO NPs) are finding increasing utility in the medical field as anticancer agents. Before validation of in vivo anticancer efficacy can occur, a better understanding of whole-animal toxicity is required. We compared the toxicity of seven widely used semiconductor MO NPs made from zinc oxide (ZnO), titanium dioxide, cerium dioxide and tin dioxide prepared in pure water and in synthetic seawater using a five-day embryonic zebrafish assay. We hypothesized that the toxicity of these engineered MO NPs would depend on physicochemical properties. Significant agglomeration of MO NPs in aqueous solutions is common making it challenging to associate NP characteristics such as size and charge with toxicity. However, data from our agglomerated MO NPs suggests that the elemental composition and dissolution potential are major drivers of toxicity. Only ZnO caused significant adverse effects of all MO particles tested, and only when prepared in pure water (point estimate median lethal concentration = 3.5-9.1 mg/L). This toxicity was life stage dependent. The 24 h toxicity increased greatly (~22.7 fold) when zebrafish exposures started at the larval life stage compared to the 24 hour toxicity following embryonic exposure. Investigation into whether dissolution could account for ZnO toxicity revealed high levels of zinc ion (40-89% of total sample) were generated. Exposure to zinc ion equivalents revealed dissolved Zn2+ may be a major contributor to ZnO toxicity.
104 citations
TL;DR: The available data suggest that the extracts of S. mombin and F. exasperata proved to be capable of ameliorating indomethacin-induced gastric ulceration and the probable mechanisms are via antioxidative and proton pump inhibition.
Abstract: This study investigated the quantitative polyphenolic constituents and gastroprotective effects of aqueous leaf extracts of Spondias mombin and Ficus exasperata against indomethacin-induced gastric ulcer in rats. Ulceration was induced by a single oral administration of indomethacin (30 mg/kg body weight). Wistar rats were pretreated with esomeprazole (reference drug) at a dose of 20 mg/kg body weight, S. mombin or F. exasperata at 100 and 200 mg/kg body weight once daily for 21 days prior to ulcer induction. At the end of the experiment, gastric secretions and antioxidant parameters were evaluated. We observed that the significantly increased (p < 0.05) ulcer index, gastric volume, malondialdehyde level and pepsin activity were effectively reduced following treatment with S. mombin and F. exasperata. The extracts also markedly attenuated the reduced activity of superoxide dismutase as well as pH and mucin content in the ulcerated rats. These findings are indicative of gastroprotective and antioxidative potentials of the extracts which is also evident in the degree of % inhibition against ulceration. The available data in this study suggest that the extracts of S. mombin and F. exasperata proved to be capable of ameliorating indomethacin-induced gastric ulceration and the probable mechanisms are via antioxidative and proton pump inhibition.
101 citations
TL;DR: Treatment with CUR effectively counteracts diabetes-induced, oxidative stress mediated hepatic damage and could act as a therapeutic in lessening liver dysfunction in diabetic subjects.
Abstract: Curcumin (CUR) is a highly pleiotropic molecule and possesses anti-inflammatory, hypoglycemic, antioxidative, wound-healing and antimicrobial activities. The present study was carried out to investigate whether CUR plays any beneficial role in streptozotocin (STZ) induced hepatic pathophysiology in diabetic rats. STZ exposure increased hepatic damage associated serum markers (ALT, ALP and LDH) as well as NO production in the liver tissue. Moreover, the same exposure enhanced ROS generation and lipid peroxidation; reduced GSH levels and antioxidant enzyme activities. Hyperglycemia induced hepatic pathophysiology also activated stress response pathways (involving phosphorylation of p38, ERK1/2 MAPKs and p53) and reduced mitochondrial membrane potential which in turn led to cellular apoptosis as evidenced from increased hepatic DNA fragmentation as well as FACS analysis. However, treatment with CUR effectively counteracts diabetes-induced, oxidative stress mediated hepatic damage and could act as a therapeutic in lessening liver dysfunction in diabetic subjects.
97 citations
TL;DR: The effects of hesperidin in iron induced hepatic and renal function and its reduced lipid profile were evaluated to rescue the liver and kidney tissues from pathology.
Abstract: The present study was to evaluate the protective role of hesperidin (HDN) against iron-induced hepatic and renal toxicity in rats. Administration of iron (30 mg/kg body weight) intraperitoneally for 10 days, the levels of serum hepatic markers, renal functional markers, lipid profile, lipid peroxidation markers and iron concentration in blood were significantly (p < 0.05) increased. The toxic effect of iron was also indicated by significant (p < 0.05) decrease in the levels of plasma, liver and kidney of enzymatic and non-enzymatic antioxidants. Administration of hesperidin at different doses (20, 40 and 80 mg/kg body weight) significantly (p < 0.05) reversed the levels of serum hepatic markers, renal functional markers, lipid profile, lipid peroxidation markers, restored the levels of hepatic, renal enzymatic antioxidants and non-enzymatic antioxidants with decrease in iron concentration in blood. Hesperidin at a dose of 80 mg/kg body weight exhibits significant protection on hepatic and renal when compared with other two doses (20 and 40 mg/kg body weight). All these changes were corroborating by histological observations of liver and kidney. This study demonstrated the protective role of hesperidin in reducing toxic effects of iron in experimental rats.
97 citations
TL;DR: (sub)cellular toxicity of triclosan (TCS) on six types of mammalian cells is shown, showing regression of pancreatic islets to pycnotic cells and uncoupled respiration.
Abstract: Effects of triclosan (5-chloro-2'-(2,4-dichlorophenoxy)phenol) on mammalian cells were investigated using human peripheral blood mono nuclear cells (PBMC), keratinocytes (HaCaT), porcine spermatozoa and kidney tubular epithelial cells (PK-15), murine pancreatic islets (MIN-6) and neuroblastoma cells (MNA) as targets. We show that triclosan (1-10 μg ml-1) depolarised the mitochondria, upshifted the rate of glucose consumption in PMBC, HaCaT, PK-15 and MNA, and subsequently induced metabolic acidosis. Triclosan induced a regression of insulin producing pancreatic islets into tiny pycnotic cells and necrotic death. Short exposure to low concentrations of triclosan (30 min, ≤1 μg/ml) paralyzed the high amplitude tail beating and progressive motility of spermatozoa, within 30 min exposure, depolarized the spermatozoan mitochondria and hyperpolarised the acrosome region of the sperm head and the flagellar fibrous sheath (distal part of the flagellum). Experiments with isolated rat liver mitochondria showed that triclosan impaired oxidative phosphorylation, downshifted ATP synthesis, uncoupled respiration and provoked excessive oxygen uptake. These exposure concentrations are 100-1000 fold lower that those permitted in consumer goods. The mitochondriotoxic mechanism of triclosan differs from that of valinomycin, cereulide and the enniatins by not involving potassium ionophoric activity.
TL;DR: Principal component analysis (PCA) showed that the intrinsic properties of each extract was the most important factor defining the difference or similarity in potency to the reference acetyl-cholinesterase inhibitor while ‘dose response’ was the second most important factors.
Abstract: The chemical inhibition of acetyl-cholinesterase (AChE) is a potent strategy for addressing signal related neuropathology and natural products are potential sources of compounds with such properties. Essential oil extracts from leaf, seed, stem and rhizome of four medicinal plants [Aframomum melegueta K. Schum, Crassocephalum crepidioides (Benth S. More), Monodora myristica (Gaertn.), and Ocimum gratissimum (Linn)] were tested for acetyl-cholinesterase inhibitory activity (AChEI) using Ellman's colorimentric method and compared to a reference acetyl-cholinesterase inhibitor (galantamine). The seed (IC50 = 6.71 mg/l) and leaf (IC50 = 6.54 mg/l) extracts from O. gratissimum showed values that matched the capacity of the reference inhibitor (IC50 = 6.62 mg/l). The least potent extract was rhizome extracts of A. melegueta (IC50 = 28.97 mg/l) about four times that of the reference inhibitor. Principal component analysis (PCA) showed that the intrinsic properties (bioactive ingredient factor) of each extract (PC1 = 29.50%) was the most important factor defining the difference or similarity in potency to the reference acetyl-cholinesterase inhibitor while ‘dose response’ (PC2 = 11.38%) was the second most important factor. The outstanding AChEI property of O. gratissimum extracts could largely be attributed to the high monoterpene content while the weak potency of rhizome extracts of A. melegueta may be attributed to its predominant concentrations of sesquiterpenes. Since potency could be related to interaction between bioactive components, understanding the interaction between ratios of monoterpene and sesquiterpene in extracts could be important in determining their potency for AChEI.
TL;DR: In this article, the presence of MG and GA in the seed coat of Givotia rottleriformis and their inhibitory effect on human epidermoid carcinoma (A431) skin cancer cells were not reported.
Abstract: Gallic acid (GA) and its derivative methyl gallate (MG) are well studied plant phenolics. They have exhibited anticancer effects in several cancer cell lines. However, the presence of GA/MG in the seed coats of Givotia rottleriformis and their inhibitory effect on human epidermoid carcinoma (A431) skin cancer cells were not reported. In this study we have isolated and chemically characterized the bioactive compounds GA and MG from the bioassay guided methanolic (MeOH) seed coat extracts of G. rottleriformis. The fractions obtained from open silica column chromatography were subjected to in vitro enzymatic assays. Among seven fractions we found that only fractions 5 and 6 showed significant inhibition activity toward COX-1 with an IC50 value of 28 μg/mL and 9.3 μg/mL and COX-2 with an IC50 value of 35 μg/mL and 7.0 μg/mL respectively. However, we could not find 5-LOX enzyme inhibition activity. MG (10 mg/g DW) and GA (6 mg/g DW) were the major compounds of seed coats. Cell viability was analyzed by 3-(4,5-dimethylthiazol-2-yl)-2,5-diphenyl tetrazolium bromide (MTT) assay, which showed that GA/MG significantly reduced the growth of A431 cells with an IC50 value of 25 μg/mL and 53 μg/mL and 11 μg/mL and 43 μg/mL at 24 h and 48 h, respectively. However the cytotoxic effect of GA/MG on HaCaT normal skin keratinocyte cell line was found to be less. Western blot analysis has shown that GA/MG treatment down regulated Bcl-2 and up regulated cleaved caspase-3 with respect to increasing doses. Our results conclude that GA and MG have potential anticancer effects and can be used as therapeutic agents for skin cancers.
TL;DR: Clinical pathology indicative of liver injury was present in males that received 50mg/kg and correlated with histomorphological liver changes that included both hypertrophic and degenerative/necrotic lesions, which were seen in the livers of females at 500 mg/kg.
Abstract: Ammonium 2,3,3,3-tetrafluoro-2-(heptafluoropropoxy)-propanoate, developed for use as a polymerization processing aid in the manufacture of fluoropolymers, was tested for its potential chronic toxicity and carcinogenicity in a 2-year oral dosing study in Sprague–Dawley rats. Male rats were given daily doses of either 0, 0.1, 1 or 50 mg/kg; females were given either 0, 1, 50 or 500 mg/kg. Body weights, food consumption and clinical signs were monitored daily; clinical pathology was conducted at designated intervals and animals were given a complete pathological evaluation after 12 months and 24 months of dosing. Normal survival was seen in all groups, no abnormal clinical signs were seen, and body weight gain was reduced only in female rats at 500 mg/kg. Both sexes at the high dose had mild decreases in red cell mass which were somewhat more pronounced in females. Clinical pathology indicative of liver injury was present in males that received 50 mg/kg and correlated with histomorphological liver changes that included both hypertrophic and degenerative/necrotic lesions. Similar histomorphological lesions were seen in the livers of females at 500 mg/kg. Previous shorter term toxicity studies have identified this chemical as a PPARα agonist and the finding of benign tumors of the liver, pancreas and/or testes in males at 50 mg/kg and females at 500 mg/kg is consistent with the rat response to peroxisome proliferators and is of questionable human relevance. Changes in the kidney, tongue, and stomach were observed only at the highest dose of 500 mg/kg in females. The no-observed-adverse-effect-level in this study lies between 1 and 50 mg/kg for males and between 50 and 500 mg/kg for females.
TL;DR: Experimental data support the notion that Cr(VI) caused mitochondrial damage, apoptosis, oxidative stress, and subsequently lead to a strong induction of HO1, GCLC and SOD2 via the Nrf-2 signaling pathway in hepatocytes.
Abstract: Hexavalent chromium, Cr(VI), is an environmental toxicant and is associated with hepatotoxicity. However, very little is known about the intracellular antioxidant defense mechanism against Cr(VI)-induced cytotoxicity in hepatocytes. In the present study, we cultured human liver (HepG2) cells in the absence or presence of Cr(VI) and determined its effect on cellular oxidative stress, mitochondrial damage, apoptosis and the expression of the transcription factor Nrf2 and the Nrf2-dependent antioxidant enzymes. Cr(VI) intoxication at a dose of 0, 3.125, 6.25, 12.5, 25, or 50 μM for 24 h exhibited a dose dependent cytotoxic effects in hepatocytes. Besides, Cr(VI) induced oxidative stress and subsequent mitochondrial damage. Cr(VI) also induced caspase 3-dependent apoptosis in HepG2 cells. In addition, Cr(VI) induced the translocation of Nrf2 into the nucleus and up-regulated the expression of Nrf2-dependent antioxidant enzymes, including SOD2, GCLC, and HO1. Our present experimental data support the notion that Cr(VI) caused mitochondrial damage, apoptosis, oxidative stress, and subsequently lead to a strong induction of HO1, GCLC and SOD2 via the Nrf-2 signaling pathway in hepatocytes.
TL;DR: The results suggest that soft drinks in Nigeria may be contaminated with heavy metals which constitute a major public health problem and quality control is recommended during the production process especially at the stages of sterilization and purification.
Abstract: Soft drinks are consumed daily in Nigeria due to its affordability, characteristic taste, and thirst quenching potential. However, the high demand may compromise the quality of production with possible contamination of heavy metals which have shown to cause intoxication and death in humans. This study evaluated some constituents of twenty-six soft drinks in Nigeria and investigated the presence of some heavy metal contaminants. The soft drinks were screened for the presence of sugar, carbon dioxide, phosphate and alcohol as well as the pH and acidity determined. The level of cadmium, mercury and lead were determined using atomic absorption spectrophotometer. The study showed the presence of sugar, carbon dioxide, phosphate, and alcohol in the soft drinks. The soft drinks were acidic in nature, pH ranging from 3 to 5 with a mean of 3.6 and the acid concentration was relatively low between 3 and 12 g/L with a mean of 8.1 g/L. Lead was present in all the samples ranging from 0.17 to 3.39 mg/L with a mean of 0.8, mercury was present in 22 samples ranging from 0.29 to 11.32 mg/L with a mean of 2.08 mg/L while cadmium was present only in one sample (0.149 mg/L). When compared to EPA, WHO and NIS standards, the levels of the heavy metal contaminants were above the tolerated limits for good quality drinking water in most samples. These results suggest that soft drinks in Nigeria may be contaminated with heavy metals which constitute a major public health problem. Thus, quality control is recommended during the production process especially at the stages of sterilization and purification.
TL;DR: The transient formation of organometallic derivatives could adequately explain the observed cadmium selective filtration in cigarettes with carbon filters and lead levels in a worldwide sample of 568 cigarettes are presented.
Abstract: Arsenic, cadmium and lead levels in tobacco filler and cigarette smoke were determined in a 568-sample worldwide survey. Median tobacco levels for arsenic, cadmium and lead were 237, 769 and 397 ng/g respectively, comparable to those previously reported albeit somewhat lower for lead and cadmium. Median mainstream smoke yields for arsenic, cadmium and lead were <3.75, 18.2, and <12.8 ng/cig. under ISO, and <8.71, 75.1 and <45.7 ng/cig. under Health Canada Intense (HCI) smoking regime respectively. In the case of cigarettes with activated carbon, a selective retention of cadmium but not lead or arsenic was observed. This effect was more pronounced under ISO than under HCI smoking regimes. Cadmium selective retention by activated carbon was confirmed by testing specially designed prototype cigarettes and the causes for this selective filtration were investigated. The differences between cadmium, arsenic and lead in terms of their speciation in tobaccos and in cigarette smoke could be related to their distribution in the ash, butt, mainstream (in gas-phase and particulate-phase) and sidestream smoke of a smoked cigarette. The possible formation of organometallic cadmium derivatives in the smoke gas-phase is discussed, the presence of which could adequately explain the observed cadmium selective filtration.
TL;DR: Exposing cells to nanosilver particles (AgNPs) immediately induces ROS, and smaller AgNPs induce mitochondrial ROS production, independent of particle internalisation.
Abstract: Silver nanoparticles (AgNPs) induce the production of reactive oxygen species (ROS) and apoptosis. These effects are enhanced by smaller particles. Using live-cell imaging, we show that AgNPs induced ROS production rapidly in a size-dependent manner after exposure of cells to 70-nm and 1-nm AgNPs (AgNPs-70, AgNPs-1), but not AgNO3. Exposure of cells to 5 μg/mL each of AgNPs-70, AgNPs-1 or AgNO3 for 1 h decreased the cell viability by approximately 40%, 100% and 20%, respectively. ROS were rapidly induced after 5 and 60 min by AgNPs-1 and AgNPs-70, respectively, whereas AgNO3 had no detectable effect. ROS production detected using the reporter dichlorodihydrofluorescein was observed in whole cells and mitochondria 5 and 60 min after exposure to AgNPs-1. The present study is the first, to our knowledge, to report the temporal expression and intracellular localisation of ROS induced by AgNPs.
TL;DR: The study shows that a single hepatotoxic dose of CCl4 is equally neurotoxic to rats, which implies vulnerability of the brain for CCl 4 neurotoxicity.
Abstract: Carbon tetrachloride (CCl4), a hepatotoxic agent is widely used to study the toxic mechanisms in experimental animals. We have investigated whether oxidative stress is induced in the brain at a single hepatotoxic dosage (1 ml/kg bw) of CCl4. Increased lipid peroxidation (LPO), protein carbonyls (PC) content and glutathione (GSH) depletion were observed in the brain regions of rats treated with CCl4 which was higher than that of liver. A drastic reduction in the activity of glutathione-S-transferase (GST) was seen in the brain regions which was higher than that of liver. Similarly, activities of glutathione peroxidase (GPx), glutathione reductase (GR), superoxide dismutase (SOD), catalase (CAT), NADH- and NADPH-dehydrogenase were reduced in the brain regions similar to that of liver. Higher induction of oxidative stress in the brain compared to that of liver implies vulnerability of the brain for CCl4 neurotoxicity. Our study shows that a single hepatotoxic dose of CCl4 is equally neurotoxic to rats.
TL;DR: It is suggested that concomitant use of NsL oil with tramadol proved to be capable of ameliorating tramadl-induced hepato- and nephrotoxicity which might be due to its antioxidant potential.
Abstract: The present study was carried out to evaluate the role of Nigella sativa Linn ( NsL ) oil against subacute tramadol-induced hepatotoxicity, nephrotoxicity as well as oxidative stress in adult male albino rats. Sixty adult male albino rats were divided into four groups. Group I: control group; 30 rats equally subdivided into: Ia; −ve control group, Ib; +ve control group received saline, Ic; +ve control group received corn oil. Group II: 10 rats received NsL oil; 1 mg/kg in 1 ml corn oil/day, group III: 10 rats received tramadol; 30 mg/kg/day, group IV: 10 rats received tramadol + NsL oil in the previous doses. Treatments were given by gavage for 30 days. Then rats were sacrificed and specimens from the livers and kidneys were taken for biochemical and histopathological study. Biochemical data showed elevated liver enzymes; alanine transaminase (ALT), aspartate transaminase (AST), gamma glutamyltransferase (GGT), bilirubin as well as urea and creatinine in tramadol group. A significant increase in hepatic and renal malondialdehyde (MDA) and a decrease in glutathione peroxidase (GPx) levels were also noticed. Histological analysis of the liver showed vacuolated hepatocyte cytoplasm indicating hydropic degeneration with binucleated cells, apoptotic nuclei, congested central veins, cellular infiltration and hemorrhage. Kidney sections revealed atrophied glomeruli with collapsed tufts and wide Bowman's space, degenerated tubules, hemorrhage and mononuclear cellular infiltration. There was also an increase in area % of collagen fibers in both organs. Concomitant use of NsL oil with tramadol induced partial improvement in the hepato- and nephrotoxic effects. In conclusion, this study suggested that concomitant use of NsL oil with tramadol proved to be capable of ameliorating tramadol-induced hepato- and nephrotoxicity which might be due to its antioxidant potential.
TL;DR: It could be concluded that CNPs is a promise candidate as drug delivery enhances the protective effect of Q against the cytogenetic effects of AFB1 in high endemic areas.
Abstract: The aims of the current study were to prepare chitosan nanoparticles (CNPs) and to evaluate its protective role alone or in combination with quercetin (Q) against AFB 1 -induce cytotoxicity in rats. Male Sprague-Dawley rats were divided into 12 groups and treated orally for 4 weeks as follow: the control group, the group treated with AFB 1 (80 μg/kg b.w.) in corn oil, the groups treated with low (140 mg/kg b.w.) or high (280 mg/kg b.w.) dose of CNPs, the group treated with Q (50 mg/kg b.w.), the groups treated with Q plus the low or the high dose of CNPs and the groups treated with AFB 1 plus Q and/or CNPs at the two tested doses. The results also revealed that administration of AFB 1 resulted in a significant increase in serum cytokines, Procollagen III, Nitric Oxide, lipid peroxidation and DNA fragmentation accompanied with a significant decrease in GPx I and Cu–Zn SOD-mRNA gene expression. Q and/or CNPs at the two tested doses overcome these effects especially in the group treated with the high dose of CNPs plus Q. It could be concluded that CNPs is a promise candidate as drug delivery enhances the protective effect of Q against the cytogenetic effects of AFB 1 in high endemic areas.
TL;DR: Evidence of reactive oxygen species (ROS) production with two different surface chemical compositions of AgNPs supported the hypothesis that the toxic effect AgNps exposure is due to overproduction of ROS which altered the gene expression and protein modifications.
Abstract: Silver nanoparticles (AgNPs) are gaining rapid popularity in many commonly used medical and commercial products for their unique anti-bacterial properties. The molecular mechanisms of effects of AgNPs on stem cell self-renewal and proliferation have not yet been well understood. The aim of the work is to use mouse embryonic stem cells (mESCs) as a cellular model to evaluate the toxicity of AgNPs. mESC is a very special cell type which has self-renewal and differentiation properties. The objective of this project is to determine the effects of AgNPs with different surface chemical compositions on the self-renewal and cell cycle of mESCs. Two different surface chemical compositions of AgNPs, polysaccharide-coated and hydrocarbon-coated, were used to test their toxic effects on self-renewal and proliferation of mESCs. The results indicated that both polysaccharide-coated and hydrocarbon-coated AgNPs changed the cell morphology of mESCs. Cell cycle analysis indicated that AgNPs induced mESCs cell cycle arrest at G1 and S phases through inhibition of the hyperphosphorylation of Retinoblastoma (Rb) protein. Furthermore, AgNPs exposure reduced Oct4A isoform expression which is responsible for the pluripotency of mESCs, and induced the expression of several isoforms OCT4B-265, OCT4B-190, OCT4B-164 which were suggested involved in stem cell stresses responses. In addition, the evidence of reactive oxygen species (ROS) production with two different surface chemical compositions of AgNPs supported our hypothesis that the toxic effect AgNPs exposure is due to overproduction of ROS which altered the gene expression and protein modifications. Polysaccharide coating reduced ROS production, and thus reduced the AgNPs toxicity.
TL;DR: Investigating the preventive effects of ginger and turmeric rhizomes on some biomarkers of male reproductive function in L-NAME-induced hypertensive rats revealed significant decrease in serum total testosterone and epididymal sperm progressive motility without affecting sperm viability in hypertensive Rats.
Abstract: Ginger [Zingiber officinale Roscoe (Zingiberaceae)] and turmeric [Curcuma longa Linn (Zingiberaceae)] rhizomes have been reportedly used in folk medicine for the treatment of hypertension. However, the prevention of its complication such as male infertility remains unexplored. Hence, the aim of the present study was to investigate the preventive effects of ginger and turmeric rhizomes on some biomarkers of male reproductive function in L-NAME-induced hypertensive rats. Male Wistar rats were divided into seven groups (n = 10): normotensive control rats; induced (L-NAME hypertensive) rats; hypertensive rats treated with atenolol (10 mg/kg/day); normotensive and hypertensive rats treated with 4% supplementation of turmeric or ginger, respectively. After 14 days of pre-treatment, the animals were induced with hypertension by oral administration of L-NAME (40 mg/kg/day). The results revealed significant decrease in serum total testosterone and epididymal sperm progressive motility without affecting sperm viability in hypertensive rats. Moreover, increased oxidative stress in the testes and epididymides of hypertensive rats was evidenced by significant decrease in total and non-protein thiol levels, glutathione S-transferase (GST) activity with concomitant increase in 2',7'-dichlorofluorescein (DFCH) oxidation and thiobarbituric acid reactive substances (TBARS) production. Similarly, decreased testicular and epididymal NO level with concomitant elevation in arginase activity was observed in hypertensive rats. However, dietary supplementation with turmeric or ginger efficiently prevented these alterations in biomarkers of reproductive function in hypertensive rats. The inhibition of arginase activity and increase in NO and testosterone levels by both rhizomes could suggest possible mechanism of action for the prevention of male infertility in hypertension. Therefore, both rhizomes could be harnessed as functional foods to prevent hypertension-mediated male reproductive dysfunction.
TL;DR: DPPH forms purple color when dissolved in solution and its color is altered to slightly yellowish color with the intervention of rhizome extracts of Curcuma caesia Roxb with different concentrations showing the scavenging activity against the free radicals generated by DPPH.
Abstract: The rhizomes of Curcuma caesia Roxb. (zingiberacea) are traditionally used in treatment of various ailments and metabolic disorders like leukoderma, asthma, tumours, piles, bronchitis, etc. in Indian system of medicine. Considering the importance of natural products in modern phytomedicine, the antioxidant and antimutagenic activities of C. caesia Roxb. rhizome extract and its fractions were evaluated. The ethanolic fraction showed highest antioxidant activity by DPPH assay (86.91%) comparable to ascorbic acid (94.77%) with IC50 value of 418 μg/ml for EECC followed by MECC (441.90 μg/ml) > EAECC(561 μg/ml) > AECC(591 μg/ml). Based on the antioxidant activity, three of the rhizome extracts were evaluated for their antimutagenic properties against indirect acting mutagen cyclophosphamide (CP) using Salmonella typhimurium strains TA98 and TA100. The antimutagenic activity of the extracts against indirect acting mutagen cyclophosphamide in the presence of mammalian metabolic activation system was found to be significant (p < 0.01, p < 0.05). All the extracts showed similar antimutagenicity in dose dependent manner. The total phenolic content as well as reducing ability of the extracts was also determined.
TL;DR: In this article, a bio-factant from Candida utilis was used in the formulation of a mayonnaise, which was biologically tested on rats and in different formulations.
Abstract: Biosurfactants have a number of industrial applications due their diverse properties, such as emulsification, foaming, wetting, and surface activity. The aim of the present study was to produce a biosurfactant from Candida utilis and employ it in the formulation of a mayonnaise. The biosurfactant was produced in a mineral medium supplemented with glucose and canola waste frying oil at 150 rpm for 88 h. The product was biologically tested on rats and in different formulations of mayonnaise, which were submitted to microbiological evaluations. The biosurfactant was added to the diet of the rats for 21 days. Greater consumption was found of the experimental diet. Moreover, no changes were found in the liver or kidneys of the animals, demonstrating the absence of a toxic effect from the biosurfactant. Six different formulations of mayonnaise were prepared and tested regarding stability with the addition of carboxymethyl cellulose and guar gum (combined and isolated) after 30 days of refrigeration. The most stable formulation with the best quality was obtained with combination of guar gum and the isolated biosurfactant, with an absence of pathogenic microorganisms. In conclusion, the potential and innocuousness of the biosurfactant isolated from C. utilis indicates its safe use in food emulsions.
TL;DR: Oral exposure to a mixture of the endocrine disruptors BPA and phthalates, relevant for human exposure, would accelerate diabetes development compared to BPA alone, apparently in part via systemic immune alterations including decreased macrophage function.
Abstract: Type 1 diabetes mellitus (T1DM) is an autoimmune destruction of insulin producing pancreatic beta-cells due to a genetic predisposition and can be triggered by environmental factors. We have previously shown that bisphenol A (BPA) accelerates the spontaneous development of diabetes in non-obese diabetic (NOD) mice. Here, we hypothesized that oral exposure to a mixture of the endocrine disruptors BPA and phthalates, relevant for human exposure, would accelerate diabetes development compared to BPA alone. NOD mice were exposed to BPA (1. mg/l), a mixture of phthalates (DEHP 1. mg/l, DBP 0.2. mg/l, BBP 10. mg/l and DiBP 20. mg/l) or a combination of BPA and the phthalate mixture through drinking water from conception and throughout life. Previous observations that BPA exposure increased the prevalence of diabetes and insulitis and decreased the number of tissue resident macrophages in pancreas were confirmed, and extended by demonstrating that BPA exposure also impaired the phagocytic activity of peritoneal macrophages. None of these effects were observed after phthalate exposure alone. The phthalate exposure in combination with BPA seemed to dampen the BPA effects on macrophage number and function as well as diabetes development, but not insulitis development. Exposure to BPA alone or in combination with phthalates decreased cytokine release (TNFα, IL-6, IL-10, IFNγ, IL-4) from in vitro stimulated splenocytes and lymph node cells, indicating systemic changes in immune function. In conclusion, exposure to BPA, but not to phthalates or mixed exposure to BPA and phthalates, accelerated diabetes development in NOD mice, apparently in part via systemic immune alterations including decreased macrophage function. © 2015 The Authors.
TL;DR: The results suggest that Roundup® may be inhibitory to hypothalamic–pituitary axis leading to reduction in cyclic adenosine monophosphate (cAMP)/PKA pathway, StAR phosphorylation and corticosterone synthesis in the adrenal tissue.
Abstract: The effect of Roundup® on adrenal gland steroidogenesis and signaling pathway associated with steroid production was investigated Doses of 10, 50, 100 and 250 mg/kg bw/d Roundup® were administered for two weeks to adult male rats The 10 mg/kg bw/d dose which reduced circulatory corticosterone levels, but did not change food consumption and body weight, was selected for further study The expression of cholesterol receptor (low density lipoprotein receptor), de novo cholesterol synthesis enzyme (3-hydroxy-3-methylglutaryl-coenzyme A synthase), hormone-sensitive lipase, steroidogenic acute regulatory protein (StAR) mRNA and phosphorylated form was decreased Adrenocorticotropic hormone receptor (ACTH), melanocortin-2 receptor, expression was not changed but circulatory ACTH levels and adrenal cortex protein kinase A (PKA) activity were reduced Surprisingly, exogenous ACTH treatment rescued steroidogenesis in Roundup®-treated animals Apoptosis was evident at 250 mg/kg bw/d, but not at 10 mg/kg bw/d dose These results suggest that Roundup® may be inhibitory to hypothalamic-pituitary axis leading to reduction in cyclic adenosine monophosphate (cAMP)/PKA pathway, StAR phosphorylation and corticosterone synthesis in the adrenal tissue
TL;DR: In this article, the authors used a zebrafish model to link the herbicide paraquat (PQ) to disease etiology and showed that exposure to PQ during the window of dopamine neurogenesis causes Parkinsonian like motor defects in later life by perturbing cholinergic system due to oxidative stress.
Abstract: Exposure to environmental risk factors such as herbicides in early life has been proposed to play important roles in the development of neurodegenerative disorders in adult life. To test this hypothesis, we used a zebrafish model to link the herbicide paraquat (PQ) to disease etiology. Strikingly, treatment of 18 hpf embryonic zebrafish with low-dose PQ treatment (0.04 ppm, lower than the accepted human daily exposure) resulted in 50% display of neurodegenerative phenotypes and motor deficits at various developmental stages (segmentation to larval stage). Wide arrays of biomarkers have been employed to delineate the toxic responses which include lipid peroxidation, glutathione (GSH) and apoptosis studies. A decrease in the GSH levels, increase in lipid peroxidation and apoptosis, respectively, were observed at various developmental stages. Unexpectedly, we show that the exposure to paraquat during the window of dopamine neurogenesis causes Parkinsonian like motor defects in later life by perturbing cholinergic system due to oxidative stress.
TL;DR: The biochemical, molecular and histological findings of the present study demonstrate that oxidative stress and inflammation play vital role in 5-FU induced GI toxicity and the inhibitory potential of vit.
Abstract: Damage to the mucous membrane is a serious issue associated with chemotherapy. Gastrointestinal (GI) toxicity is complex and multistep process and unregulated production of reactive oxygen species (ROS) and inflammatory mediators play vital role in the development of GI toxicity. In the present study we have investigated the attenuating potential of vitamin C (vit. C) on 5 fluorouracil (5-FU) induced GI toxicity by targeting oxidative stress and inflammatory markers in Sprague Dawley (SD) rats. Rats were gavaged with vit. C (500 mg/kg b. wt.) or vehicle daily (day 1-10) and were given intraperitoneal injection of 5-FU (150 mg/kg b. wt.) or saline (control) on day 8 to induce mucositis. We found that vit. C supplementation attenuated 5-FU induced lipid peroxidation, myeloperoxidase (MPO) activity, activation of NF-kB and expression of COX-2. Histological observations further supported the protective potential of vit. C against 5-FU induced intestinal anomalies such as neutrophil infiltration, loss of cellular integrity, villus and crypt deformities. Thus the biochemical, molecular and histological findings of the present study demonstrate that oxidative stress and inflammation play vital role in 5-FU induced GI toxicity and the inhibitory potential of vit. C is may be due to the modulation of oxidative stress, activation of redox sensitive transcription factor and also its downstream target molecules.
TL;DR: This study shows similarity (p > 0.05) in the distribution of Cd, Hg and Pb among fish species; and a non-uniform distribution of toxic trace metals within fish organs with Kidney > Liver > Gill ≥ Intestine ≥ Muscle.
Abstract: The distribution of non-essential trace elements in some vital organs of 11 fish species from Aiba Reservoir, Iwo, Nigeria was assessed between November 2010 and June 2011 The fish species belong to seven families; family Mormyridae, family Cyprinidae, family Hepsetidae and family Channidae each with one species; family Bagridae and family Clariidae each with two species; and family Cichlidae with three species All families, except Clariidae and Channidae, are common in the daily catch from the reservoir Atomic absorption spectrophotometry was used to determine the levels of cadmium, mercury and lead in fish organs The concentration of toxic trace metals in fish ranged from 0001 to 0100 ppm (Cd), 0000–0067 ppm (Hg) and 0001–0125 ppm (Pb) dry weight This study shows similarity (p > 005) in the distribution of Cd, Hg and Pb among fish species; and a non-uniform distribution of toxic trace metals within fish organs with Kidney > Liver > Gill ≥ Intestine ≥ Muscle Canonical variate analysis shows clear discrimination of Clarias macromystax and Channa obscura for gill trace metal levels of Cd, Hg and Pb while Labeo senegalensis and Oreochromis niloticus were discriminated for liver trace metal values of Cd and Pb only when compared to other fish species studied The discrimination of some fish species based on trace metals in the gills and liver suggests different regulatory strategies for trace metal accumulation Variation due to comparison among different fish species from the same water body suggests that accumulation may be species dependent Differential accumulation of toxic trace metals in fish organs makes them good bioindicators of freshwater contamination