Showing papers in "Drug and Chemical Toxicology in 2015"

Linalool as a neuroprotective agent against acrylamide-induced neurotoxicity in Wistar rats

Abstract: Acrylamide (ACR) is a water-soluble monomer which has broad application in different industries and also can form in food during heating process. This monomer is a potent neurotoxic and damages the central and the peripheral nervous system in human and animals. Oxidative stress has been mentioned as an important pathway in ACR neurotoxicity, therefore the purpose of the current study was evaluation of possible effects of linalool which is a naturally enantiomer monoterpene compound. Linalool has shown antioxidant properties in several studies. Male Wistar rats were treated with ACR (50 mg/kg ip) alone or with linalool (12.5, 25, 50 and 100 mg/kg ip) for 11 days. In another 2 groups rats were treated with linalool (12.5 mg/kg ip) 3 days after and before ACR administration. Then behavior index (gait score) was examined for rats. After that, rats were sacrified and molondialdehyde (MDA) as a marker of lipid peroxidation and glutathione (GSH) content were determined in brain tissue. Exposure to ACR le...

Boron attenuates malathion-induced oxidative stress and acetylcholinesterase inhibition in rats.

Abstract: Organophosphorus compounds cause oxidative stress and lead to alterations in antioxidant status in organisms. In this study, the effects of subchronic exposure to malathion and the protective effects of boron (B) were evaluated in 48 Wistar rats, which were divided equally into six groups. For 28 d, the control group received a normal diet and tap water, the corn oil group received a normal diet and 0.5 mL of corn oil by gastric gavage and the malathion group received a normal diet and malathion (100 mg/kg/d) by gastric gavage. During the same period, each of the three other groups received a different dosage of B (5, 10 and 20 mg/kg/d, respectively) and malathion (100 mg/kg/d) by gastric gavage. Malathion administration during the period increased malondialdehyde, nitric oxide and 8-hydroxy-2′-deoxyguanosine (8-OHdG) levels, as well as markers of liver function, yet decreased acetylcholinesterase, reduced glutathione, superoxide dismutase, and catalase activities in blood, liver, kidney and brain...

Cisplatin hepatotoxicity mediated by mitochondrial stress

Abstract: Context: Chemotherapy has long been the keystone of cancer regimen, and comprehensive research has been done on the development of more potent and less toxic anti-cancer agents. Cisplatin (CP) is a potent and extensively used chemotherapeutic agent. There is paucity of literature involving role of mitochondria in mediating CP-induced hepatic toxicity, and its underlying mechanism remains unclear. Oxidative stress is a well-established biomarker of the mitochondrial toxicity. Objective: This study evaluates the dose-dependent effects of CP-induced mitotoxicity under in vitro conditions, using mitochondria from rat liver. Materials and methods: The aim of our study was to determine the effect of CP with different concentrations in isolated liver mitochondria as an in vitro model. Results: CP exposure showed significantly compromised level of non enzymatic and enzymatic antioxidants with higher extent of lipid and protein oxidation. CP also caused significant alterations in the activity of respirator...

2C-I-NBOMe, an "N-bomb" that kills with "Smiles". Toxicological and legislative aspects.

Abstract: Substituted phenethylamines are a class of designer drugs that have recently emerged in the drug abuse market. Such substances remain legal to use, possess, and supply until these compounds become classified as scheduled. 2C-I-NBOMe or 25I-NBOMe is the N-benzyl-derivative of the iodo-substituted dimethoxy-phenethylamine (2C-I) that appeared recently in the drug market under the street name “N-Bomb”. Due to its high potency, intoxications and fatal cases related to 2C-I-NBOMe use are increased worldwide. The use and trafficking of this substituted phenethylamine is banned only in some countries. A comprehensive review was performed using PubMed and Medline databases, together with additional non-peer reviewed information sources, including books and publications of state authorities in different countries, regarding chemistry, availability, pharmacology, and toxicology of 2C-I-NBOMe. Intoxications or lethal cases, published or reported, as well as the current legislation on this newly introduced dr...

Protective effect of L-Theanine against aluminium induced neurotoxicity in cerebral cortex, hippocampus and cerebellum of rat brain – histopathological, and biochemical approach

Abstract: L-Theanine is an amino acid derivative primarily found in tea. It has been reported to promote relaxation and have neuroprotective effects. The present study was designed to investigate the role of oxidative stress and the status of antioxidant system in the management of aluminum chloride (AlCl3) induced brain toxicity in various rat brain regions and further to elucidate the potential role of L-Theanine in alleviating such negative effects. Aluminium administration significantly decreased the level of reduced glutathione and the activities of superoxide dismutase, catalase, glutathione peroxidase, glutathione reductase, Na+/K+ ATPase, Ca2+ ATPase and Mg2+ ATPase and increased the level of lipid peroxidation and the activities of alkaline phosphatase, acid phosphatase, alanine transaminase and aspartate transaminase in all the brain regions when compared with control rats. Pre-treatment with L-Theanine at a dose of 200 mg/kg b.w. significantly increased the antioxidant status and activities of me...

Acute toxicity of some nerve agents and pesticides in rats

Abstract: Objectives: Highly toxic organophosphorus compounds (V- and G-nerve agents) were originally synthesized for warfare or as agricultural pesticides. Data on their acute toxicity are rare and patchy. Therefore, there is a need for integrated summary comparing acute toxicity of organophosphates using different administration routes in the same animal model with the same methodology. Based on original data, a summary of in vivo acute toxicity of selected V- and G-nerve agents (tabun, sarin, soman, VX, Russian VX) and organophosphates paraoxon (POX) and diisopropyl fluorophosphate (DFP) in rats has been investigated. Materials and methods: Male Wistar rats were exposed to organophosphates in several administration routes (i.m., i.p., p.o, s.c., p.c.). The acute toxicity was evaluated by the assessment of median lethal dose (LD50, mg kg−1) 2, 4, and 24 hours post exposure. Results: V-agents were the most toxic presented with LD50 ranged from 0.0082 mg kg−1 (VX, i.m.) to 1.402 mg kg−1 (Russian VX, p.o.), ...

The effect of five artificial sweeteners on Caco-2, HT-29 and HEK-293 cells.

Abstract: Context: Artificial sweeteners (AS) have been associated with tumor development (including colon cancer) in both animals and humans although evidence has been conflicting. Objectives: Additional research was thus conducted by studying the effects of 5 AS on the morphology, cell proliferation and DNA in cells by utilizing Caco-2, HT-29 (colon) and HEK-293 (kidney) cell lines. Materials and methods: Cells were exposed to sodium cyclamate, sodium saccharin, sucralose and acesulfame-K (0–50 mM) and aspartame (0–35 mM) over 24, 48 and 72 hours. Morphological changes were presented photographically and % cell viability was determined by using the MTT cell viability assay. Possible DNA damage (comet assay) induced by the AS (0.1, 1 and 10 mM, treated for 24, 48 and 72 hours) was studied. The appearance of “comets” was scored from no damage to severe damage (0–4). Results: Cells became flatter and less well defined at higher AS concentrations (>10 mM). At concentrations >10 mM, decreased cell viability wa...

In vitro toxicological assessment of iron oxide, aluminium oxide and copper nanoparticles in prokaryotic and eukaryotic cell types.

Abstract: Metallic nanoparticles (NPs) have a variety of applications in different industries including pharmaceutical industry where these NPs are used mainly for image analysis and drug delivery. The increasing interest in nanotechnology is largely associated with undefined risks to the human health and to the environment. Therefore, in the present study cytotoxic and genotoxic effects of iron oxide, aluminium oxide and copper nanoparticles were evaluated using most commonly used assays i.e. Ames assay, in vitro cytotoxicity assay, micronucleus assay and comet assay. Cytotoxicity to bacterial cells was assessed in terms of colony forming units by using Escherichia coli (gram negative) and Bacillus subtilis (gram positive). Ames assay was carried out using two bacterial strains of Salmonella typhimurium TA98 and TA100. Genotoxicity of these NPs was evaluated following exposure to monkey kidney cell line, CHS-20. No cytotoxic and genotoxic effects were observed for iron oxide, and aluminium oxide NPs. Copper NPs were found mutagenic in TA98 and in TA100 and also found cytotoxic in dose dependent manner. Copper NPs induced significant (p < 0.01) increase in number of binucleated cells with micronuclei (96.6 ± 5.40) at the highest concentration (25 µg/mL). Copper NPs also induced DNA strand breaks at 10 µg/mL and oxidative DNA damage at 5 and 10 µg/mL. We consider these findings very useful in evaluating the genotoxic potential of NPs especially because of their increasing applications in human health and environment with limited knowledge of their toxicity and genotoxicity.

Chronic diclofenac (DCF) exposure alters both enzymatic and haematological profile of African catfish, Clarias gariepinus.

Abstract: Pharmaceuticals are used extensively in human and veterinary medicine to eradicate or prevent diseases. The residues of these drugs have been detected in aquatic ecosystem; nevertheless, their toxicological effects on Clarias gariepinus have not been critically investigated. In this study, the toxic effects of diclofenac (DCF), a non-steroid anti-inflammatory drug, were studied in C. gariepinus by acute and chronic static renewable bioassay. The 96 h LC50 of DCF to C. gariepinus was 25.12 mg/L. Exposure to acute toxicity resulted in abnormal behavior and mortality of some fish. Compared with the control, chronic exposure of the fish to concentration (1.57, 3.14 and 6.28 mg/L) showed significantly higher mean corpuscular haemoglobin concentration (MCHC), mean corpuscular volume (MCV) and white blood cell (WBC), with significantly lower haemoglobin (Hb), haematocrit, red blood cell (RBC) and mean corpuscular haemoglobin (MCH) with increase in the concentration of the drug. Furthermore, the levels of...

Gestational lead exposure induces developmental abnormalities and up-regulates apoptosis of fetal cerebellar cells in rats.

Abstract: Lead (Pb), a known environmental toxicant, adversely affects almost all organ systems. In this study, we investigated the effects of maternal lead exposure on fetal rat cerebellum. Female Sprague–Dawley rats were given lead nitrate in drinking water (0, 0.5, and 1%) for two weeks before conception, and during pregnancy. Fetuses were collected by caesarian section on gestational day 21 and observed for developmental abnormalities. The fetal cerebellar sections from control and 1% lead group were stained with cresyl violet. Immunohistochemical expressions of p53, Bax, Bcl-2, and caspase 3 were quantified by AnalySIS image analyzer (Life Science, Germany). Lead exposure induced developmental abnormalities of eyes, ear, limbs, neck and ventral abdominal wall; however, these abnormalities were commonly seen in the 1% lead-treated group. In addition, lead also caused fetal mortality and reduced body growth in both dose groups and reduced brain weight in the 1% lead-treated group. The fetal cerebella fro...

SiO2 Nanoparticule-induced size-dependent genotoxicity – an in vitro study using sister chromatid exchange, micronucleus and comet assay

Abstract: Fine particles with a characteristic size smaller than 100 nm (ie nanoparticlesspread out in nowadays life Silicon or Si, is one of the most abundant chemical elements found on the Earth Its oxide forms, such as silicate (SiO4) and silicon dioxide, also known as silica (SiO2), are the main constituents of sand and quartz contributing to 90% of the Earth's crust In this work, three genotoxicity systems “sister chromatid exchange, cytokinesis block micronucleus test and single cell gel electrophoresis (comet) assay” were employed to provide further insight into the cytotoxic and mutagenic/genotoxic potential of SiO2 nanoparticules (particle size 6 nm, 20 nm, 50 nm) in cultured peripheral blood lymphocytes as in vitro It was observed that there is a significant decrease in Mitotic index (MI), Cytokinesis block proliferation index (CBPI), proliferation index (PRI) values expressed as Cell Kinetic parameters compared with negative control (p < 005) There is a statistically significant differenc

Lipid metabolism disturbances contribute to insulin resistance and decrease insulin sensitivity by malathion exposure in Wistar rat

Abstract: Several studies showed that organophosphorus pesticides disturb glucose homeostasis and can increase incidence of metabolic disorders and diabetes via insulin resistance. The current study investigates the influence of malathion on glucose metabolism regulation, in vivo, during subchronic exposure. Malathion was administered orally (200 mg/kg), once a day for 28 consecutive days. Plasma glucose, insulin and Glycated hemoglobin levels were significantly increased while hepatic glycogen content was decreased in intoxicated animals compared with the control group. Furthermore, there was a significant disturbance of lipid content in subchronic treated and post-treated rats deprived of malathion for one month. In addition, we used the homeostasis model assessment (HOMA) to assess insulin resistance (HOMA-IR) and pancreatic β-cell function (HOMA-β). Our results show that malathion increases insulin resistance biomarkers and decreases insulin sensitivity indices. Statistical analysis demonstrates that th...

Immunotoxicity assessment of sub-chronic oral administration of acetamiprid in Wistar rats.

Abstract: Context: Neonicotinoid insecticides are synthetic analogues of nicotine that acts on the central nervous system of insects by blocking post synaptic acetylcholine receptor. Acetamiprid is one of the widely used neonicotinoid class of insecticide used to control sucking insects like aphids, bees, mosquitoes, on crops. Data on the possible immunotoxic nature of acetamiprid are lacking. Objective: The present study was conducted in Wistar rats with the objective of evaluating the immunotoxic potential of acetamiprid administered orally at the dose levels of 27.5, 55 and 110 mg/kg b.w. (equivalent to 5.5, 11 and 22 mg/kg b.w.) for a period of 90 days. Materials and methods: In experiment 1, general toxicity testing including the evaluation of clinical signs, hemato-biochemical changes, response of the lymphocytes towards T and B cell mitogens, macrophage function, gross and histopathology of the lymphoid organs (spleen, thymus, lymph nodes, etc.) were performed. In the second experiment, humoral and c...

Oxidative stress and biochemical responses in the tissues of African catfish Clarias gariepinus juvenile following exposure to primextra herbicide

Abstract: Primextra is a commercial herbicide formulation generally used in agriculture for weed control. The present study was designed to investigate the oxidative stress biomarkers and biochemical responses in the tissues of Clarias gariepinus juvenile exposed to primextra. Fish were exposed to 0.24 and 0.47 mgL−1 corresponding to 1/20 and 1/10th of 96 h LC50 of the herbicide. The liver and muscle tissues were sampled on day 1, 5, 10 and 15 and results showed concentration and time dependent significant increase (p < 0.05) in the values of lipid peroxidation, glutathione peroxidase, catalase and alkaline phosphatase in both tissues. A marked significant increase (p < 0.05) was observed in the values of aspartate aminotransferase, alanine aminotransferase and glucose in the liver while a mixed trend in their values were observed in the muscle. The values of superoxide dismutase and protein in both tissues were comparable to the control except on day 15 in the liver where the values significantly declined....

Using urinary 1-hydroxypyrene concentrations to evaluate polycyclic aromatic hydrocarbon exposure in women using biomass combustion as main energy source

Abstract: Context: The use of solid fuels for cooking and heating is likely to be the largest source of indoor air pollution on a global scale. Objective: The aim of this study was to investigate the urinary excretion of 1-hydroxypyrene (1-OHP) in women living in a rural community, where biomass combustion is used as main energy source during a working day. Materials and methods: The study was performed on urine samples collected in 2012, of 30 healthy women who were residents of a rural community in San Luis Potosi, Mexico. Urine was collected from each woman at three time points (morning, post-lunch and evening) during a working day. The analysis of urinary 1-OHP was performed using high-performance liquid chromatography (HPLC). Also, a health-risk assessment was conducted. Results: The highest levels of 1-OHP in this study were found in the samples taken in the evening (geometric mean ± SD; 0.36 ± 0.13 µg/g creatinine). However, no significant differences among 1-OHP concentrations in the evening and pos...

Acute toxicity studies of a novel excipient arabinoxylan isolated from Ispaghula (Plantago ovata) husk

Abstract: Purpose: The arabinoxylan from Ispaghula (Plantago ovata) husk has been proven scientifically as potential excipient. However, toxicity study of the arabinoxylan is still lacking. The present study was done to investigate the acute toxicity of arabinoxylan in two animal species. Methods: The mice were exposed to (1 g/kg, 5 g/kg, 10 g/kg) and rabbits (2.5 g/kg, 5 g/kg) of arabinoxylan orally and observed for a period of 14 days. On day 15 hematology, serum biochemistry and necropsy was performed in mice relative organ weight calculated and histological examination was carried out. Primary dermal and eye irritation tests were carried out. Cardiac effects of isolated arabinoxylan were studied on frog heart. Results: The acute administration of the arabinoxylan did not produce mortality or significant changes in, water and food consumption however body weights of mice and rabbits decreased initially with a gradual increase till day 14. Internal organs relative weights were found to be normal. Hematolo...

Chemometrics models for assessment of oxidative stress risk in chrome-electroplating workers.

Abstract: Oxidative stress is the main cause of hexavalant chromium-induced damage in chrome electroplating workers. The main goal of this study is toxicity analysis and the possibility of toxicity risk categorizing in the chrome electroplating workers based on oxidative stress parameters as prognostic variables. We assessed blood chromium levels and biomarkers of oxidative stress such as lipid peroxidation, thiol (SH) groups and antioxidant capacity of plasma. Data were subjected to principle component analysis (PCA) and artificial neuronal network (ANN) to obtain oxidative stress pattern for chrome electroplating workers. Blood chromium levels increased from 4.42 ppb to 10.6 ppb. Induction of oxidative stress was observed by increased in lipid peroxidation (22.38 ± 10.47 μM versus 14.74 ± 4.82 μM, p < 0.0008), decreased plasma antioxidant capacity (3.17 ± 1.35 μM versus 7.74 ± 4.45 μM, p < 0.0001) and plasma total thiol (SH groups) (0.21 ± 0.07 μM versus 0.45 ± 0.41 μM, p < 0.0042) in comparison to contro...

Dose dependent cytotoxicity of pranoprofen in cultured human corneal endothelial cells by inducing apoptosis.

Abstract: Pranoprofen (PPF), a non-steroidal anti-inflammatory drugs (NSAIDs), is often used in keratitis treatment in clinic. Several studies have assessed in vitro the cytotoxicity of topical NSAIDs to corneal epithelial cells due to its importance for predicting human corneal toxicity. Damage by cytotoxic drugs can result in excessive loss of human corneal endothelial (HCE) cells which lead to decompensation of the endothelium and eventual loss of visual acuity. However, the endothelial cytotoxicity of PPF has not yet been reported using an in vitro model of HCE cells. This study assessed the cytotoxicity of PPF to HCE cells and its underlying mechanism. Cellular viability was determined using inverted phase contrast light microscopy, and plasma membrane permeability, genomic DNA fragmentation, and ultrastructure were detected by acridine orange/ethidium bromide staining, DNA agarose gel electrophoresis, and transmission electron microscopy (TEM), respectively. The results on cellular viability showed th...

Protective effects of silymarin on epirubicin-induced mucosal barrier injury of the gastrointestinal tract.

Abstract: Mucositis is a serious disorder of the gastrointestinal tract that results from cancer chemotherapy. We investigated the protective effects of silymarin on epirubicin-induced mucosal barrier injury in CD-1 mice. Immunohistochemical activity of both pro-apoptotic Bax and anti-apoptotic Bcl-2 markers, together with p53, cyt-P450 expression and DNA damage analysis on stomach, small intestine and colon were evaluated. Our results indicated stronger expression for cyt P450 in all analyzed gastrointestinal tissues of Epi group, which demonstrate intense drug detoxification. Bax immunopositivity was intense in the absorptive enterocytes and lamina connective cells of the small intestine, surface epithelial cells of the stomach and also in the colonic epithelium and lamina concomitant with a decreased Bcl-2 expression in all analyzed tissues. Epirubicin-induced gastrointestinal damage was verified by a goblet cell count and morphology analysis on histopathological sections stained for mucins. In all analy...

Comparison of TGF-β, PDGF, and CTGF in hepatic fibrosis models using DMN, CCl4, and TAA

Abstract: Three chemotoxins including dimethylnitrosamine (DMN), carbon tetrachloride (CCl4), and thioacetamide (TAA) are commonly used in hepatofibrotic models. We aimed to draw characteristics of histopathology and pro-fibrogenic cytokines including TGF-β, PDGF and CTGF among three models. Rats were divided into six groups and intra-peritoneally injected with DMN (10 mg/kg, for three weeks, three consecutive days weekly), CCl4 (1.6 g/kg, for 10 weeks, twice weekly), TAA (200 mg/kg, for 12 weeks, twice weekly) or their corresponded treatment for each control group. The liver weights were decreased in DMN model, but not other models. Ascites were occurred as 3-, 2-, and 7-rats in DMN, CCl4, and TAA model, respectively. The lipid peroxidation was highest in CCl4 model, serum levels of liver enzymes were increased as similar severity. The hepatofibrotic alterations were remarkable in DMN and TAA model, but not CCl4 as evidenced by the Masson trichrome staining and hydroxyproline. The immunohistochemistry for α-SAM showed that the DMN model was most severely enhanced than other models. On the other hand, hepatic tissue levels of pro-fibrogenic cytokines including TGF-β, PDGF, and CTGF were generally increased in three models, but totally different among models or measurement resources. Especially, serum levels of three cytokines were remarkably increased by CCl4 injection and CTGF levels in both hepatic tissue and serum were highest in CCl4 group. Our results firstly demonstrated comparative study for features of morphological finding and pro-fibrogenic cytokines in serum and hepatic protein levels among three models. Above results would be a helpful reference for hepatofibrotic studies.

Physiological functions and pharmacological and toxicological effects of p-octopamine.

Abstract: p-Octopamine occurs naturally in plants, invertebrates and animals with diverse functions and effects. This review summarizes the chemistry, metabolism, receptor binding characteristics, known physiological functions, and pharmacological and toxicological effects of p-octopamine. Databases used included PubMed and Google Scholar Advanced. p-Octopamine binds to neuroreceptors in insects that are not present in humans, while exhibiting poor binding to α-1, α-2, β-1, and β-2 adrenergic receptors in mammalian systems. p-Octopamine modestly binds to β-3 adrenergic receptors and may therefore promote lipolysis and weight loss. p-Octopamine is produced in brain and nerve tissues of mammals and is present and can be measured in the blood of normal human subjects. p-Octopamine is considered to be a CNS stimulant in spite of the fact that it binds poorly to adrenergic receptors. Variations occur in blood levels in association with neurological and hepatic diseases. Its precise role in normal neurophysiology...

Protecting effect of caffeine against vinblastine (an anticancer drug) induced genotoxicity in mice.

Abstract: Vinblastine a DNA non-intercalating agent has wide application against several human neoplasms, and found to cause cytogenotoxicity. In this study, clastogenotoxicity of vinblastine (1.5 mg/kg b w) and its prevention by caffeine at different doses (25, 50 and 100 mg/kg b w) administered intraperitoneally was assessed in in vivo mice. It was found that micronucleus level had decreased significantly (up to 28.8%) in 100 mg caffeine treated group at 30 h post treatment. However, it did not exhibit protective effect against chromosomal aberration in spaermatogonial cells at 24 h post treatment. The frequencies of aberrant primary spermatocytes had decreased significantly in 25 and 100 mg caffeine at 4th week of post treatment. Similarly, in 100 mg of caffeine administered, abnormal sperm level had reduced (4.01%) significantly at 8th week post treatment. Thus, caffeine decreased the vinblastine induced chromosomal aberrations and mitotic index in bone marrow cells. In conclusion, this study shows that...

The in vitro genotoxic and cytotoxic effects of remeron on human peripheral blood lymphocytes.

Abstract: Remeron (Mirtazapine) is an antidepressant drug which exerts its action by blocking presynaptic α-2-adrenergic receptors and postsynaptic serotonin types 2 and 3 receptors. In this in vitro analysis, human peripheral blood lymphocytes was treated by remeron (10, 25, 40 and 55 μg/mL) for 24 hours and 48 hours periods, then it was attempted to study of genotoxic and cytotoxic effects of the substance on human peripheral blood lymphocytes by some tests such as sister chromatid exchange (SCE), chromosomal abnormalities (CA) and micronucleus (MN) tests. Also proliferating effect of the substance was investigated. Remeron didn’t significantly cause chromosomal abnormalities and sister chromatid exchange while caused micronucleus at 40 μg/mL concentration and 24 h periodic time and increased proliferation index of the both 24 and 48 hours treated cells was decreased in a concentration manner. Also, exposing to the remeron for 24 and 48 hours leaded to a decrease in mitotic index and nucleus division inde...

Prenatal developmental toxicity evaluation of Withania somnifera root extract in Wistar rats.

Abstract: Context: Withania somnifera (L) Dunal (Solanaceae) is an important traditional herbal medicine used for thousands of years and is considered as the Indian ginseng. Reports on the effect of Withania somnifera root (WSR) extract on the developing foetus of pregnant rats including mortality, structural abnormalities, changes in growth and effects on dams are not available. Objective: The present study was performed to evaluate the prenatal developmental toxicity potential of WSR extract in rats. Materials and methods: WSR extract was given orally to pregnant rats during the period of major organogenesis and histogenesis (days 5 to 19 of gestation) at the dose levels of 500, 1000 and 2000 mg/kg/day. Clinical observations including mortality, moribundity, behavioural changes, signs of overt toxicity, body weight, gross pathological changes of dams and foetal analyses including external malformations, skeletal and soft tissue malformations were evaluated. Results: No evidence of maternal or foetal toxic...

Mechanisms of interaction of the N-acetyl-p-aminophenol metabolites in terms of nephrotoxicity.

Abstract: Context: Epidemiological studies have demonstrated that chronic use of N-acetyl-p-aminophenol is correlated with the occurrence of renal dysfunction. Objective: Aim of this study was to review the literature on the mechanisms of interaction N-acetyl-p-aminophenol metabolites in terms of nephrotoxicity. Methods: We present a literature review of studies published in English language on the damage effects of N-acetyl-p-aminophenol on the kidneys, accessed through PubMed database. Results: The pathogenesis of drug-induced nephrotoxicity attributed to the action of cytochrome P450 enzymes, prostaglandin endoperoxide synthase (PGES) and N-deacetylase. The metabolism of N-acetyl-p-aminophenol with the participation of PGES more explicit is in the core of kidney, whereas cytochrome P450 enzymes play role in the renal cortex. Due to the action of cytochrome P450 and N-deacetylase, a very reactive N-acetyl-p-benzochinoimine (NAPQI) is formed. The result of the catalytic activity of PGES is p-benzoquinone (...

Anti-genotoxic effect of naringin against bleomycin-induced genomic damage in human lymphocytes in vitro

Abstract: Naringin is a flavonoid found in grapefruit and other citrus fruits that shows antioxidant activity. The aim of the present study was to determine the anti-genotoxic and protective effects of naringin on the chemotherapeutic/radiomimetic agent bleomycin (BLM) in human blood lymphocyte cultures in vitro using micronucleus test and chromosomal aberrations (CA) assay. We tested the three doses of naringin (1, 2, 3 µg/mL) and a single dose of BLM (20 µg/mL). BLM significantly increased the total CAs and micronucleus frequency at a concentration of 20 µg/mL. Naringin did not show any toxicity in doses of 1, 2, and 3 µg/mL. Combined treatments of BLM and naringin (2 and 3 µg/mL) significantly reduced micronucleus formation. Naringin dose-dependently decreased the total chromosome aberrations frequency induced by BLM. These results indicate that naringin could prevent BLM (20 µg/mL)-induced genotoxicity.

The effects of Andrographis paniculata (Burm.f.) Nees extract and diterpenoids on the CYP450 isoforms’ activities, a review of possible herb–drug interaction risks

Abstract: Andrographis paniculata (Burm.f.) Nees is a popular medicinal plant and its components are used in various traditional product preparations. However, its herb-drug interactions risks remain unclear. This review specifically discusses the various published studies carried out to evaluate the effects of Andrographis paniculata (Burm.f.) Nees plant extracts and diterpenoids on the CYP450 metabolic enzyme and if the plant components pose a possible herb-drug interaction risk. Unfortunately, the current data are insufficient to indicate if the extracts or diterpenoids can be labeled as in vitro CYP1A2, CYP2C9 or CYP3A4 inhibitors. A complete CYP inhibition assay utilizing human liver microsomes and the derivation of relevant parameters to predict herb-drug interaction risks may be necessary for these isoforms. However, based on the current studies, none of the extracts and diterpenoids exhibited CYP450 induction activity in human hepatocytes or human-derived cell lines. It is crucial that a well-defined experimental design is needed to make a meaningful herb-drug interaction prediction.

Assessment of genotoxic and mutagenic potential of hexavalent chromium in the freshwater fish Labeo rohita (Hamilton, 1822).

Abstract: The present study was undertaken to investigate the genotoxicity and mutagenicity of sublethal concentrations of hexavalent chromium (potassium dichromate) in the Indian major carp, Labeo rohita. The 96 h LC50 value of potassium dichromate estimated was 118 mg L−1 by probit analysis using SPSS (version 16.0) software. Based on 96 h LC50 value, three sublethal test concentrations of potassium dichromate (29.5, 59.0 and 88.5 mg L−1) were selected and specimens were exposed in vivo to these test concentrations for 96 h. The mutagenic and genotoxic effects of potassium dichromate were evaluated in gill and blood cells using micronucleus (MN) test and comet assay. In general, significant (p < 0.05) effects due to the concentrations and the exposure durations were observed in exposed specimens. The MN induction was highest at 96 h at all the test concentrations in the peripheral blood. A similar trend was observed for the DNA damage, measured in terms of percentage of tail DNA, in erythrocyte and gill c...

Exposure to 2,5-hexanedione is accompanied by ovarian and uterine oxidative stress and disruption of endocrine balance in rats

Abstract: 2,5-Hexanedione (2,5-HD) is an aliphatic diketone identified as the main neurotoxic metabolite of the industrial chemicals n-hexane and methyl-n-butyl ketone. Considering the dearth of information on the female reproductive toxicity effects of 2,5-HD in the literature, we assessed the potential oxidative stress mechanisms of 2,5-HD in the ovary and uterus of Wistar rats. A total of 32 female rats were randomly allotted to four groups, in which rats were exposed to 2,5-HD at doses of 0% (control), 0.25%, 0.5% and 1.0% respectively in their drinking water for 21 days. The results showed that 2,5-HD significantly increased ovarian and uterine malondialdehyde (MDA) and hydrogen peroxide (H2O2) levels (p < 0.05). Additionally, while significant decreases in ovarian catalase, superoxide dismutase (SOD), glutathione peroxidase (GPx), and glutathione-S-transferase (GST) activities occurred in all the 2,5-HD-treated groups, uterine catalase, GST, and GPx activities increased. Further, 2,5-HD increased foll...

Effects of histidine and n-acetylcysteine on experimental lesions induced by doxorubicin in sciatic nerve of rats.

Abstract: In this study, the effect of separate and combined intraperitoneal (i.p.) injections of histidine and n-acetylcysteine were investigated on experimental damage induced by doxorubicin (DOX) in sciatic nerve of rats. DOX was i.p. injected at a dose of 4 mg/kg once weekly for four weeks. Histidine and n-acetylcysteine were i.p. injected at a same dose of 20 mg/kg. Cold and mechanical allodynia were recorded using acetone spray and von Frey filaments tests, respectively. The sciatic nerve damage was evaluated by light microscopy. Plasma levels of malondialdehyde (MDA) and total antioxidant capacity (TAC) were measured. Histidine and especially n-acetylcysteine at a same dose of 20 mg/kg suppressed cold and mechanical allodynia, improved sciatic nerve lesions and reversed MDA and TAC levels in DOX-treated groups. Combination treatment with histidine and n-acetylcysteine showed better responses when compared with them used alone. The results of the present study showed peripheral neuroprotective effects...