Showing papers in "Toxicology reports in 2023"

Preparation and characterization of activated carbon from agricultural wastes and their ability to remove chlorpyrifos from water

Abstract: Chlorpyrifos is an organophosphate insecticide linked to neurological dysfunctions, endocrine disturbance, cardiovascular illness, genotoxicity, histopathological abnormalities, immunotoxicity, and oxidative stress. Therefore, the aim of this study was to prepare activated carbon from agricultural waste to adsorb and remove chlorpyrifos from aqueous solutions, as well as to study the physicochemical characteristics of the prepared activated carbon.Activated carbon was prepared from agricultural waste (banana peels, orange peels, pomegranate peels and date stones). The activated carbon prepared showed an exterior surface that was irregular and full of cavities with Brunauer-Emmett-Teller(BET) surface areas of 94.26, 111.75, 183.89, and 289.86 m2/g for activated carbon prepared from orange peels, date stone, pomegranate peels, and banana peels respectively. The Scanning Electron Microscope (SEM) image revealed that the activated carbon's exterior surface was irregular and full of various shapes and sizes of cavities.The Energy Dispersive X-Ray (EDX) indicated the existence of carbon, oxygen, silicon and potassium in banana peels-derived activated carbon, whereas carbon, oxygen, silicon and potassium, in addition to aluminium, were detected in the pomegranate peels-derived activated carbon. The Fourier-Transform Infrared Spectroscopy (FTIR) analysis of prepared activated carbon revealed several functional groups, including carboxylic acid, carbon dioxide, and aromatic compounds. Results also showed that the activated carbon significantly removed chlorpyrifos from water, recording 97.6%, 90.6%, 71.48%, and 52.00 % for activated carbon prepared from pomegranate peels, banana peels, date stones and orange peels, respectively. The study concluded that agricultural waste-derived activated carbon could be employed as an alternative pesticide adsorbent.

Apoptosis, inflammation, and oxidative stress in infertility: A mini review

Abstract: Infertility has been a major issue in our society for many years, and millions of couples all over the world are still experiencing it. There are several reasons for and causes of infertility in both men and women. Recent studies have shown that apoptosis, inflammation, and oxidative stress contribute immensely to infertility. The data regarding this report were obtained through a thorough review of scientific articles published in various databases, including Elsevier, Web of Science, PubMed, Scopus, and Google Scholar. Furthermore, PhD and MSc theses were also reviewed when compiling the data. Apoptosis, also known as "programmed cell death," is a natural and harmless process that occurs in human beings. Although it can become harmful if altered, Inflammation, on the other hand, is the body's reaction to detrimental stimuli caused by toxic substances or compounds, while oxidative stress is a phenomenon that results in an imbalance between the generation and aggregation of reactive oxygen species (ROS) in the cells against antioxidants. These three factors interchangeably bring about several reproductive disorders in the body, resulting in infertility. This review aims at discussing how apoptosis, inflammation, and oxidative stress play a role in human infertility.The datasets used and/or analyzed during the current study are available from the corresponding author upon reasonable request.

Potential human health risks associated with ingestion of heavy metals through fish consumption in the Gulf of Guinea

Abstract: Heavy metal pollution of the marine environment has toxic implications for both the aquatic biota and human health. We examined the levels of Zinc (Zn), Lead (Pb), Copper (Cu), Cadmium (Cd), Arsenic (As) and Mercury (Hg) in muscles of Sardinella maderensis, Dentex angolensis, Sphyraena sphyraena and Penaeus notialis caught from the coastal waters of Ghana using inductively coupled plasma mass spectrometry method. Penaeus notialis recorded the highest concentrations of all the metals (Cu:12.08 ± 1.46 µg/g, Zn: 19.20 ± 2.27 µg/g, As: 8.46 ± 2.42 µg/g, and Cd: 0.03 ± 0.01 µg/g) except Hg. Mercury was relatively high in D. angolensis (0.14 ± 0.03 µg/g). Apart from As, all metals were within globally permissible daily limits for consumption by human per meal. The estimated Target Hazard Quotient due to the intake of Hg through D. angolensis consumption exceeded the threshold value across all age categories. Carcinogenic risks due to As intake through P. notialis consumption far exceeded the 10−6 threshold for all age groups in Ghana. It is recommended that the consumption of these fish species particularly, the shrimp P. notialis be done cautiously to avoid possible future health challenges.

The use of aflibercept (VEGF trap) in mitigating sulfur mustard-induced corneal neovascularization in a rabbit model

Abstract: Sulfur mustard (SM)-induced ocular injury is characterized by an acute inflammatory response that may become chronic or enter a latent phase with delayed pathology. This study aimed to evaluate the efficacy of ziv-aflibercept and aflibercept in preventing and ameliorating corneal neovascularization (NV), respectively, following chemical eye exposure to SM vapor in a rabbit model. Chemical SM ocular insult was induced in the right eye of rabbits. A single application of ziv-aflibercept was administered 2 h or 9 days post-exposure. A single subconjunctival aflibercept treatment in an ocular formulation was administered 4 weeks after SM vapor exposure and subsequent to an initial 1-week treatment with 0.1 % dexamethasone. Clinical monitoring was performed 5-12 weeks post-exposure, and digital corneal pictures were taken to assess the extent of NV. The rabbits were euthanized and the corneas were processed for histological assessment. Treatment with ziv-aflibercept 2 h and 9 days post-exposure moderately reduced insult severity and partially delayed or prevented corneal NV. Aflibercept application 4 weeks post-exposure significantly reduced the extent of NV for 8 weeks. The substantial decrease in existing corneal NV in this group was confirmed by histology. These results reveal the powerful anti-angiogenic efficacy of the VEGF-trap for ameliorating existing NV as opposed to preventing NV development, revealing the ability of this treatment to mitigate corneal NV.

Chemical and in vitro toxicological comparison of emissions from a heated tobacco product and the 1R6F reference cigarette

Abstract: It has previously been found that, compared with cigarette smoke, the aerosols generated by heated tobacco products contain fewer and lower harmful and potentially harmful constituents (HPHCs) and elicit lower biological activity in in vitro models and lower smoking-related exposure biomarker levels in clinical studies. It is important to accumulate such scientific evidences for heated tobacco products with a novel heating system, because different heating system may affect the quantitative aspect of the amount of HPHCs and the qualitative aspect of the biological activity of the aerosol generated. Here, the chemical properties of, and toxicological responses to aerosols emitted by DT3.0a, a new heated tobacco product with a novel heating system, and cigarette smoke (CS) were compared, using chemical analyses, in vitro battery (standardized genotoxicity and cytotoxicity) assays, and mechanistic (ToxTracker and two-dimensional cell culture) assays. Regular- and menthol-flavored DT3.0a and standard 1R6F reference cigarettes were tested. Selected HPHC yields were lower in DT3.0a aerosol than 1R6F CS. The genotoxicity-related assays indicated that DT3.0a aerosol was not genotoxic, regardless of metabolic activation. The other biological assays indicated that less cytotoxicity induction and oxidative stress response were elicited by DT3.0a aerosol compared with 1R6F CS. Similar results were found for both regular and menthol DT3.0a. Like previous reports for heated tobacco products with other heating systems, the results of this study indicated that DT3.0a aerosols have chemical and biological properties less likely to be harmful than 1R6F CS.

Acute and subchronic toxicity profile of methanol extract of leaves of Fimbristylis miliacea (L.) Vahl

Abstract: Fimbristylis miliacea (L.) Vahl (Cyperaceae) is a grass like herb habitually breeds as weed in paddy fields and mostly disseminated in tropical or sub-tropical countries of south and south-east Asia, northern Australia, and west Africa. The plant has been traditionally used to treat fever as a form of poultice. However, no scientific study regarding its toxicity profile has been testified.The study has been carried out to determine the potential toxicity of the methanol extract from leaves of the Fimbristylis miliacea, employing the technique of acute and subchronic oral administration in mice.In the acute toxicity study according to OECD guideline 425, oral administration of FM methanol extract at single doses of 2000 and 5000 mg/kg in both sexes of Swiss albino mice was performed. Toxic symptoms, abnormal behavior, changes in body weight, and mortality were observed for 14 consecutive days. In subchronic toxicity study according to OECD guideline 407, plant extract was administered orally at doses of 100, 500, 1000, and 2000 mg/kg daily for 28 days. The general toxic symptoms, abnormal behavior, changes in body weight were observed daily. Biochemical analysis of serum, and histopathological examination of liver were performed at the end of the study.No mortality, abnormal behavior and urination, changes in sleep, food intake, adverse effect, and non-linearity in body weight have been recorded during acute toxicity study at the doses of 2000 and 5000 mg/kg. Also, in subchronic toxicity study, FM extract produced no mortality or any kind of adverse effects in regards of general behavior, body weight, urination, sleeping routine, and food intake. In case of analysis of thirteen different biochemical parameters, concentrations of aspartate transaminase (AST) and glucose were altered significantly in male and female mice in both acute and subchronic study. Total cholesterol and triglycerides at 5000 mg/kg.bw were changed in male mice in acute toxicity study. On the other hand, female mice had altered triglycerides in subchronic test. All other critical parameters were found unaffected. In subchronic test, histopathological examination of liver demonstrated cellular necrosis at 2000 mg/kg.bw in both male and female mice while minor necrosis was observed at 1000 mg/kg.bw. Thus, the no observed adverse effect level (NOAEL) can be assumed around 1000 mg/kg.bw.The present study suggests that treatment with FM extract does not reveal significant toxicity.

Determination of metal(oids) in different traditional flat breads distributed in Isfahan city, Iran: Health risk assessment study by latin hypercube sampling

Abstract: This survey was conducted to assess the metal(oids) content in 93 samples of bread, including barbari, lavash, and tafton, using inductive couple plasma/optical emission spectroscopy (ICP-OES) method and atomic absorption spectroscopy (AAS). The amounts of measured element were compared with the permissible limit set for bread by FAO/WHO and Iranian National Standardization Organization (INSO). The limit of detection (LOD) was ranged from 6.6 × 10-5 to 2.1 × 10-2 mg l-1 with recoveries ranged from 92% to 102%. The average concentrations of aluminum (Al), arsenic (As), boron (B), cadmium (Cd), iron (Fe), mercury (Hg), magnesium (Mg), sodium (Na), lead (Pb), and zinc (Zn) in bread were 29.88 ± 8, 0.03 ± 0.004, 12.77 ± 3.70, 0.01 ± 0.006, 34.16 ± 8.95, 0.01 ± 0.008, 346.07 ± 36.08, 3314.81 ± 317.19, 0.24 ± 0.11, and 19.65 ± 4.66 mg Kg-1, respectively. Amounts of As, Cd, Hg, Mg, Pb, and Zn were lower, and those of Al, Fe, and Na were higher than the permissible limits defined by FAO/WHO. The Latin Hyper Cube (LHC) sampling results revealed that children were exposed to higher non-carcinogenic risk and adults were more threatened by carcinogenic risk. It is recommended to control the entrance of metals in bread in the farm-to-fork chain in order to prevent probable future health challenges.

Multivariate analysis of heavy metals content of beef from Soroti, Uganda

Abstract: Information about food hygiene and quality in the sub-Saharan African countries remains scarce at a time when many of their citizenry are beginning to acquire the much coveted middle income status. Confounding this are challenges linked to monitoring on a continuous basis the safety of food produced by such lucrative industries as the beef industry. The objective of the current study was to initiate a process of encouraging changes in the status quo, by showing how a first step in that direction might look like. Using heavy metal contents of representative beef samples from butcheries in Soroti, Uganda, typical of a sub-Saharan country, we demonstrate how relationships and common sources of metals in food could be identified in a multivariate space. Beef samples from 40 sites were analyzed by atomic absorption spectrometry for iron (Fe), zinc (Zn), nickel (Ni), chromium (Cr), lead (Pb), copper (Cu), cobalt (Co) and cadmium (Cd). The study showed that all beef samples contained these metals, the extent of which were in the order: Fe > Zn >> Ni, Cr > Pb > Cu, Co > Cd. By correlation analysis, the pairs Ni and Cr, Cd and Co, Ni and Fe or Cr and Fe were found to be most likely coming from similar sources. At least three distinct characteristics of beef consumed in Soroti were also found, a distinction perhaps arising from three major categories of feedlots used to raise donor cattle. The incremental risk of children or adults developing cancer over a lifetime was estimated and found to fall into three categories, two of which are separately explained by the presence of Cr or Ni. The sources of these metals remain a matter of speculation on our part. More studies are needed to determine these sources and to understand the nature of cancer risk in the three categories of beef identified here.

Disease-associated metabolic pathways affected by heavy metals and metalloid

Abstract: Increased exposure to environmental heavy metals and metalloids and their associated toxicities has become a major threat to human health. Hence, the association of these metals and metalloids with chronic, age-related metabolic disorders has gained much interest. The underlying molecular mechanisms that mediate these effects are often complex and incompletely understood. In this review, we summarize the currently known disease-associated metabolic and signaling pathways that are altered following different heavy metals and metalloids exposure, alongside a brief summary of the mechanisms of their impacts. The main focus of this study is to explore how these affected pathways are associated with chronic multifactorial diseases including diabetes, cardiovascular diseases, cancer, neurodegeneration, inflammation, and allergic responses upon exposure to arsenic (As), cadmium (Cd), chromium (Cr), iron (Fe), mercury (Hg), nickel (Ni), and vanadium (V). Although there is considerable overlap among the different heavy metals and metalloids-affected cellular pathways, these affect distinct metabolic pathways as well. The common pathways may be explored further to find common targets for treatment of the associated pathologic conditions.

Hepatocyte-specific damage in acute toxicity of sodium ferrous citrate: Presentation of a human autopsy case and experimental results in mice

Abstract: Acute iron overload is known to exert deleterious effects in the liver, but detailed pathology has yet to be documented. Here, we report pathological findings in an autopsy case of acute iron toxicity and validation of the findings in mouse experiments. In a 39-year-old woman who intentionally ingested a large amount of sodium ferrous citrate (equivalent to 7.5 g of iron), severe disturbance of consciousness and fulminant hepatic failure rapidly developed. Liver failure was refractory to treatment and the patient died on Day 13. Autopsy revealed almost complete loss of hepatocytes, while bile ducts were spared. To examine the detailed pathologic processes induced by excessive iron, mice were orally administered equivalent doses of ferrous citrate. Plasma aminotransferase levels markedly increased after 6 h, which was preceded by increased plasma iron levels. Hepatocytes were selectively damaged, with more prominent damage in the periportal area. Phosphorylated c-Jun was detected in hepatocyte nuclei after 3 h, which was followed by the appearance of γ-H2AX expression. Hepatocyte injury in mice was associated with the expression of Myc and p53 after 12 and 24 h, respectively. Even at lethal doses, the bile ducts were morphologically intact and fully viable. Our findings indicate that acute iron overload induces hepatocyte-specific liver injury, most likely through hydroxyl radical-mediated DNA damage and subsequent stress responses.

Pro-inflammatory effects of aerosols from e-cigarette-derived flavoring chemicals on murine macrophages.

Abstract: Macrophages treated with the flavoring chemicals found in flavored electronic cigarettes have been shown to induce an inflammatory response, however, limited data are available on the effect of aerosol exposure to these chemicals. We hypothesized that aerosol exposure to flavoring chemicals found in commercially available flavored e-liquids would result in an increase in pro-inflammatory cytokines in macrophages. Raw264.7 macrophage cell lines were exposed to a low and high dose of propylene glycol/vegetable glycerin (PG/VG) with almond flavoring benzaldehyde (280 μg/ml and 2.1 mg/ml), PG/VG with spicy/clove flavoring eugenol (3.5 mg/ml and 12 mg/ml), or PG/VG with apple flavoring hexyl acetate (500 μg/ml and 2.5 mg/ml). Exposure to PG/VG with 2.1 mg/ml benzaldehyde resulted in a significant increase in KC levels compared to air and PG/VG exposed cells. Exposure to PG/VG with both doses of hexyl acetate resulted in a significant increase in KC and IL-6 levels compared to air exposed cells. Exposure to PG/VG with both doses of eugenol resulted in a significant increase in KC and IL-6 levels compared to air and PG/VG exposed cells. These data indicate the ability of aerosol exposure to e-cigarette flavoring chemicals to significantly increase pro-inflammatory cytokine release in macrophages.

Genetic and epigenetic instability induced by betel quid associated chemicals

Abstract: Over the years, betel quid chewing and tobacco use have attracted considerable interest as they are implicated as the most likely causative risk factors of oral and esophageal cancers. Although areca nut use and betel quid chewing may lead to apoptosis, chronic exposure to areca nut and slaked lime may promote pre-malignant and malignant transformation of oral cells. The putative mutagenic and carcinogenic mechanisms may involve endogenous nitrosation of areca and tobacco alkaloids as well as the presence of direct alkylating agents in betel quid and smokeless tobacco. Metabolic activation of carcinogenic N-nitrosamines by phase-I enzymes is required not only to elicit the genotoxicity via the reactive intermediates but also to potentiate the mutagenicity with the sporadic alkylations of nucleotide bases, resulting in the formation of diverse DNA adducts. Persistent DNA adducts provides the impetus for genetic and epigenetic lesions. The genetic and epigenetic factors cumulatively influence the development and progression of disorders such as cancer. Accumulation of numerous genetic and epigenetic aberrations due to long-term betel quid (with or without tobacco) chewing and tobacco use culminates into the development of head and neck cancers. We review recent evidence that supports putative mechanisms for mutagenicity and carcinogenicity of betel quid chewing along with tobacco (smoking and smokeless) use. The detailed molecular mechanisms of the extent of accumulation and patterns of genetic alterations, indicative of the prior exposure to carcinogens and alkylating agents because of BQ chewing and tobacco use, have not yet been elucidated.

Detection of β-N-methylamino-l-alanine in postmortem olfactory bulbs of Alzheimer’s disease patients using UHPLC-MS/MS: An autopsy case-series study

Abstract: Cyanobacterial blooms produce toxins that may become aerosolized, increasing health risks through inhalation exposures. Health related effects on the lower respiratory tract caused by these toxins are becoming better understood. However, nasal exposures to cyanotoxins remain understudied, especially for those with neurotoxic potential. Here, we present a case series study evaluating exposure to β-N-methylamino-l-alanine (BMAA), a cyanobacterial toxin linked to neurodegenerative disease, in postmortem olfactory tissues of individuals with varying stages of Alzheimer's disease (AD).Olfactory bulb (Ob) tissues were collected during autopsies performed between 2014 and 2017 from six South Florida brain donors (ages 47-78) with residences less than 140 m from a freshwater body. A triple quadrupole tandem mass spectrometry (UHPLC-MS/MS) method validated according to peer AOAC International guidelines was used to detect BMAA and two BMAA isomers: 2,4-diaminobutyric acid (2,4-DAB) and N-(2-aminoethyl)glycine (AEG). Quantitative PCR was performed on the contralateral Ob to evaluate the relative expression of genes related to proinflammatory cytokines (IL-6 & IL-18), apoptotic pathways (CASP1 & BCL2), and mitochondrial stress (IRF1 & PINK1). Immunohistochemistry was also performed on the adjacent olfactory tract (Ot) to evaluate co-occurring neuropathology with BMAA tissue concentration.BMAA was detected in the Ob of all cases at a median concentration of 30.4 ng/g (Range

Ochratoxin A induces endoplasmic reticulum stress and fibrosis in the kidney via the HIF-1α/miR-155-5p link

Abstract: Ochratoxin A (OTA) is a ubiquitous fungal toxin found in agricultural products and foods that is toxic to both humans and animals. OTA mainly affects kidney, but the mechanisms underlying OTA-induced nephrotoxicity remain not fully understood. MicroRNA (miRNA) is involved in key cellular processes. The toxic mechanism and regulatory effects of miRNAs on OTA toxicity in kidney, and particularly the role of HIFα-1/miR-155-5p on OTA-caused ER stress and fibrosis, were investigated in this study. OTA induced hypoxia-like conditions such as ER stress and fibrosis in HK-2 cells and renal tissues via modulating HIF-1α, which was followed by regulation of ER stress-related proteins (GRP78 and ATF-4), as well as fibrosis-related markers (fibronectin, α-SMA, and E-cadherin). Notably, a total of 62 miRNAs showed significant differential expression in kidney of OTA-treated mice. Under OTA exposure, HIF-1α enhanced miR-155-5p expression, causing ER stress and fibrosis in HK-2 cells. HIF-1α knockdown decreased OTA-induced miR-155-5p expression as well as ER stress and fibrotic responses, whereas miR-155-5p overexpression restored this. Our data suggest that OTA enhances ER stress and fibrosis in the kidney through upregulating the HIF-1α/miR-155-5p link.

Prevalence of pesticide related occupational diseases among Indonesian vegetable farmers – A collaborative work

Abstract: This study was done to understand the prevalence of various occupational diseases including dry eyes, nail dystrophy, and neuropathy related to pesticide exposure in Indonesian local vegetable farmers. The data were collected through questionnaires and physical examination involving dermatology, neurology, and ophthalmology domains at Ngablak District, Magelang, Central Java directed to local vegetable farmers. Ocular Surface Disease Index (OSDI) questionnaire and the Schirmer test were used. Analysis was done using descriptive statistics using the Statistical Package for the Social Sciences (SPSS 21.0) and presented in tables. Inadequate spraying equipment and improper storage of pesticides were found. Out of 105 farmers, 41.9 % experienced occupational skin diseases (OSD). Definite cognitive impairments were found in 3.4 % of subjects but probable in 28.3 % of subjects. Neuropathies were found in 61.7 % of subjects, and dry-eyes syndrome were found in 28.78 % of subjects. There was a high prevalence of peripheral neuropathy and tremor, dry eyes syndrome in one-third of the population, and the most common skin problem was nail discoloration, with a low incidence of contact dermatitis.

Xanthomicrol: Effective therapy for cancer treatment.

Abstract: Cancer treatment is one of the main challenges of global health. For decades, researchers have been trying to find anti-cancer compounds with minimal side effects. In recent years, flavonoids, as a group of polyphenolic compounds, have attracted the attention of researchers due to their beneficial effects on health. Xanthomicrol is one of the flavonoids that has the ability to inhibit growth, proliferation, survival and cell invasion and ultimately tumor progression. Xanthomicrol, as active anti-cancer compounds, can be effective in the prevention and treatment of cancer. Therefore, the use of flavonoids can be suggested as a treatment along with other medicinal agents. It is obvious that additional investigations in cellular levels and animal models are still needed. In this review article, the effects of xanthomicrol on various cancers have been reviewed.

Evaluation of in vivo MRI for detecting midodrine-induced arteritis in rats

Abstract: There are no specific and sensitive biomarkers for arteritis, and the occurrence of arteritis in nonclinical toxicological studies of a candidate drug makes development of the drug very difficult. However, we showed in a previous study that the high signal intensity region around the artery on magnetic resonance imaging (MRI) could be a candidate biomarker for detection of arteritis. The present study was conducted to clarify the details of midodrine hydrochloride (MH)-induced arteritis lesions and whether arteritis induced by a mechanism other than the vasodilatory effect, which was evaluated in a previous study, could be detected by MRI. MH is a selective peripherally acting alpha-1 adrenergic receptor agonist, known to induce arteritis due to its vasoconstrictor action, but there is not enough information about MH-induced arteritis. Based on the data obtained under multiple dosing conditions, MH was administered subcutaneously to each rat once daily for 2 days at a dose level of 40 mg/kg/day for MRI assessment. The mesenteric arteries were examined using in vivo MRI at 1 day or 7 days after administration of the final dose and examined histopathologically. On the day after the final dose, high signal intensity region around the artery was observed in animals with minimal perivascular lesions confirmed by histopathology and not observed in an animal without histological changes. On the 7th day after the final dose, no abnormality was observed in histopathological examinations and no high signal intensity regions were observed by MRI in any animal. In conclusion, although further investigation is needed to confirm that high signal intensity is a reliable biomarker for humans, it is suggested that high signal intensity around the artery could be a versatile candidate biomarker with high specificity and sensitivity.

Heavy metals contamination in shrimp and crab from southwest regions in Bangladesh: Possible health risk assessment

Abstract: Shrimp and Crab, important sources of protein, are currently being adversely affected by the rising industrialization, which has led to higher levels of heavy metals. The goal of this study was to evaluate the health risks of contamination associated with nine heavy metals (Cd, Pb, Cu, Cr, Zn, Ni, As, Al, and Fe) in two species of shrimp (Macrobrachium rosenbergii and Metapenaeus monoceros) and one species of crab (Scylla serrata) that were collected from the Khulna, Satkhira, and Bagerhat areas of Bangladesh. Inductively coupled plasma-optical emission spectrometry (ICP-OES) was used for the study. The results showed that all metal concentrations in shrimp and crab samples were below the recommended level, indicating that ingestion of these foods would not pose any substantial health risks to individuals. To evaluate the non-carcinogenic health risks, the target hazard quotient (THQ) and hazard index (HI) were determined, and the target cancer risk (TR) was utilized to evaluate the carcinogenic health risks. From the health point of view, this study showed that crustaceans obtained from the study sites were non – toxic (THQ and HI < 1), and long-term, continuous intake is unlikely to pose any significant health hazards (TR = 10−7-10−5) from either carcinogenic or non-carcinogenic effects.

Protein and peptide profiles of rats’ organs in scorpion envenomation

Abstract: Problem of scorpion envenomation becomes more alarming each year. Main effects of scorpion venom are commonly believed to be related to its neurotoxic properties, yet severe symptoms may also be developed due to the uncontrolled enzymatic activity and formation of various bioactive molecules, including middle-mass molecules (MMMs). MMMs are considered as endogenous intoxication markers, their presence may indicate multiple organ failure. Scorpions, belong to the Leiurus macroctenus species, are very dangerous, nevertheless, effects of their venom on protein and peptide composition within the tissues remains unclear. In this work we have focused the attention on changes in protein and MMM levels and peptide composition in various organs during Leiurus macroctenus envenomation. The results revealed a decrease in protein level during envenomation as well as a significant increment of MMM210 and MMM254 levels in all assessed organs. Quantitative and qualitative compositions of various protein and peptide factions were continually changing. All of this may suggest that Leiurus macroctenus sting causes considerable destruction of cell microenvironment across all essential organs, providing systemic envenomation. In addition, MMM level increment may indicate endogenous intoxication development. Peptides, formed during envenomation, may possess various bioactive properties, analysis of which constitutes an area of further studies.

A new animal product free defined medium for 2D and 3D culturing of normal and cancer cells to study cell proliferation and migration as well as dose response to chemical treatment

Abstract: Cell culturing methods are increasingly used to reduce and replace the use of live animals in biomedical research and chemical toxicity testing. Although live animals are avoided when using cell culturing methods, they often contain animal-derived components of which one of the most commonly used is foetal bovine serum (FBS). FBS is added to cell culture media among other supplements to support cell attachment/spreading and cell proliferation. The safety, batch-to-batch variation, and ethical problems with FBS are acknowledged and therefore world-wide efforts are ongoing to produce FBS free media. Here, we present the composition of a new defined medium with only human proteins either recombinant or derived from human tissues. This defined medium supports long-term culturing/routine culturing of normal cells and of cancer cells, and can be used for freezing and thawing of cells, i.e. for cell banking. Here, we show for our defined medium, growth curves and dose response curves of cells grown in two and three dimensions, and applications such as cell migration. Cell morphology was studied in real time by phase contrast and phase holographic microscopy time-lapse imaging. The cell lines used are human cancer-associated fibroblasts, keratinocytes, breast cancer JIMT-1 and MDA-MB-231 cells, colon cancer CaCo-2 cells, and pancreatic cancer MiaPaCa-2 cells as well as the mouse L929 cell line. In conclusion, we present the composition of a defined medium without animal-derived products which can be used for routine culturing and in experimental settings for normal cells and for cancer cells, i.e. our defined medium provides a leap towards a universal animal product free cell culture medium.

Hibiscus sabdariffa calyx protect against oxidative stress and aluminium chloride-induced neurotoxicity in the brain of experimental rats

Abstract: We evaluated the antioxidant and neuroprotective potentials of extracts of Hibiscus sabdariffa calyx in Wistar albino male rats injected intraperitoneally with aluminium chloride at a dose of 7 mg/kg/day. Phytochemical screening of H. sabdariffa calyx show that coumarin glycosides and steroid were absent after drying at 50 oC. At 30 oC, there were significant (p < 0.05) highest amounts of phenols, flavonoids, alkaloids, tannin, and saponin. The extracts showed significantly (p < 0.05) high dose-dependent antioxidant activities. MDA significantly (p < 0.05) increased, while GSH, GPX, SOD, CAT activities significantly (p < 0.05) decreased in the brain of the experimental rats induced with AlCl3, while treatment with the extracts reversed these effects to a relatively normal level. At doses of 500 and 1000 mg/kg body weight, the extracts of the calyx dried at 30 oC exhibited the highest capacity to increase the activities of GSH and GPx. Also, AlCl3 caused significant increases (p < 0.05) in the percentage inhibition of acetylcholinesterase and butyrylcholinesterase activities, and a significantly (p < 0.05) lower protein levels in the brain of the test rats, while treatment with the extracts, at low and high doses, significantly (p < 0.05) reversed these effects in the rat brain to near normal.H. sabdariffa exhibited a good potential to protect against oxidative stress and neurotoxicity.

Acute oral toxicity assessment of galbanic acid in albino rat according to OECD 425 TG

Abstract: In spite of the broad biological and also anticarcinogenic effects which have been reported for galbanic acid in various studies, its toxic effects are not still well characterized. The study was accomplished to evaluate the acute oral toxicity of galbanic acid pursuant to Organisation for Economic Co-operation and Development (OECD) TG No. 425. Female rats were received asafoetida extract and galbanic acid in distilled water by oral gavage. According to the existing information, limit test was done for aqueous extract of asafoetida and main test was done for galbanic acid. The animals were monitored for 2 weeks. Then under general anesthesia, the blood samples were obtained from the heart for biochemical and hematological assessment and the vital organs of rats were isolated for pathological evaluation. The results showed that although the Median lethal dose (LD50) of asafoetida extract was above the 2000 mg/kg body weight, the galbanic acid estimated LD50 was 310.2 mg/kg. There was no considerable change in body weight of vehicle and extract treated animals but in galbanic acid treated animals, the body weights were not normally increased. A significant rise was observed in high-density lipoprotein (HDL), (aspartate aminotransferase) AST and (alanine aminotransferase) ALT levels as well as in white blood cells (WBC), platelet and lymphocytes counts in galbanic acid group compared to vehicle and extract groups. Based on the obtained results, we suggest that although the asafoetida aqueous extract could be categorized as group 5 (LD50 > 2000 mg/kg), but galbanic acid estimated LD50 is about 310.2 mg/kg and toxicity signs also appeared in lung, liver enzymas and complete blood count (CBC) of galbanic acid treated animals.

Effects of changing reference values on the interpretation of spirometry for rubber workers

Abstract: The National Health and Nutrition Assessment Survey (NHANES) is being adopted for interpreting spirometry in occupational examinations. Rubber workers have an elevated risk of respiratory health issues due to industrial exposure, and changes in the equations would affect spirometry monitoring programs.To determine the differences in the use of the Knudson and NHANES III equations in nonsmoking workers in the rubber industry.A cross-sectional study was conducted with 75 nonsmoking workers with occupational exposure to rubber for at least two years. The factory had engineered protection controls and provided respiratory protection to the workers. Spirometry was conducted according to Spirometry Testing in Occupational Health Programs and Standardization of Spirometry: American Thoracic Society/European Respiratory Society.Spirometric prediction differences were present in the restrictive pattern assessment based on forced vital capacity (FVC), in which three individuals (4%) classified as normal according to Knudson presented restrictive disease according to NHANES III; only in the record of one participant was there restrictive disease using both equations. There was an 8% discrepancy for small airway obstruction in which six workers classified as normal using NHANES III were classified as diseased (FEF 25-75 <50%) using the Knudson equation.In the respiratory examination of workers exposed to rubber, the NHANES III equation is better able to detect restrictive diseases than is the Knudson equation; however, the Knudson equation is more sensitive to obstructive patterns.

Bisphenols, but not phthalate esters, modulate gene expression in activated human MAIT cells in vitro

Abstract: One route of human exposure to environmental chemicals is oral uptake. This is primarily true for chemicals that may leach from food packaging materials, such as bisphenols and phthalate esters. Upon ingestion, these compounds are transported along the intestinal tract, from where they can be taken up into the blood stream or distributed to mucosal sites. At mucosal sites, mucosal immune cells and in the blood stream peripheral immune cells may be exposed to these chemicals potentially modulating immune cell functions. In the present study, we investigated the impact of three common bisphenols and two phthalate esters on mucosal-associated invariant T (MAIT) cells in vitro, a frequent immune cell type in the intestinal mucosae and peripheral blood of humans. All compounds were non-cytotoxic at the chosen concentrations. MAIT cell activation was only slightly affected as seen by flow cytometric analysis. Phthalate esters did not affect MAIT cell gene expression, while bisphenol-exposure induced significant changes. Transcriptional changes occurred in ∼ 25 % of genes for BPA, ∼ 22 % for BPF and ∼ 8 % for BPS. All bisphenols down-modulated expression of CCND2, CCL20, GZMB and IRF4, indicating an effect on MAIT cell effector function. Further, BPA and BPF showed a high overlap in modulated genes involved in cellular stress response, activation signaling and effector function suggesting that BPF may not be safe substitute for BPA.

Delayed neuropsychiatric sequelae due to long-term effects of carbon monoxide poisoning in Ethiopia: A case report

Abstract: One emergency that occurs frequently and has high morbidity is carbon monoxide poisoning. After a time of lucidity, some victims who recover from the incident of acute carbon monoxide exposure may later suffer delayed neuropsychiatric sequelae (DNS), which can include cognitive impairments, a wide range of neurological abnormalities, and affective disorders. Below, we report the first documented incident of DNS after carbon monoxide poisoning in Ethiopia. A 40-year-old male patient who developed a coma after he was exposed to burning charcoal in a closed room was admitted to Debre Tabor Comprehensive Specialized Hospital in the northwest region of Ethiopia. He stayed for 12 days during his first admission and was discharged with improvement. One month after discharge, he developed delayed neuropsychiatric sequelae, which manifested as bizarre behavior, being unable to walk unsupported, loss of concentration, and failure to control urine and feces. Brain MRI showed bilateral periventricular and frontoparietal deep white matter subcortical abnormal T1 and T2 prolongation with no restriction of diffusivity, possibly due to demyelinating disorders. He was managed with fluid therapy, benzhexol, risperidone, and rehabilitation therapy. He stayed for two weeks in our hospital and was discharged with improvement. Despite the paucity of delayed neuropsychiatric sequelae from carbon monoxide poisoning, physicians should be highly suspicious in the right situations. The precise mechanisms of delayed toxic effects, prevention measures, and treatment modalities have not yet been determined; therefore, more research and attention are required.

Drug self-poisoning in adolescents: A report of 267 cases

Abstract: The current study aims at describing a sample of adolescents admitted to a tertiary referral pediatric hospital for drug self-poisoning and to identify variables that could explain and predict a higher severity of intoxication. We retrospectively reviewed the cases of drug self-poisoning in adolescents admitted to the Bambino Gesù Children’s Hospital between January 2014 and June 2022 requiring consultation by the local Pediatric Poison Control Center (PPCC). We reported the type and class of drug ingested and correlated the clinical characteristics of the patients with their Poison Severity Score. The data of 267 patients were reported. Most patients were female (85.8 %), with a median age of 15.8 years at presentation. Half of the patients were symptomatic at admission (44.2 %), and most had at least one psychiatric comorbidity (71.1 %). Most patients were hospitalized (79.6 %), 16.6 % of cases required antidote administration and a minority required intensive care. Most patients received a PSS score of 0 (59.6 %). The most frequently ingested drug was acetaminophen (28.1 %) followed by ibuprofen (10.1 %) and aripiprazole (10.1 %). Antipsychotics as a class were the most abused drugs (33.1 %). The correlation of clinical variables with the PSS showed that older and male patients were more prone to be severely intoxicated. This single-center study identifies the most commonly ingested drugs in a large sample of adolescents with voluntary drug self-poisoning, also showing that older and male patients are more susceptible to severe intoxication.

A protein restricted diet induces a stable increased fat storage phenotype in flies

Abstract: Scientific evidence has revealed possible confounders in diet induced obesity models of Drosophila melanogaster. High Sugar Diet (HSD) induction of obesity in flies has been associated with fly hyperosmolarity and glucotoxicity, while High Fat Diet (HFD) induction has been associated with lipotoxicity. The objective of this study was to assess for a healthy obesity phenotype by comparison of fly survival, physio-chemical and biochemical changes associated with HSD, HFD and Protein Restricted Diet (PRD) obesity induction models of male Drosophila melanogaster. Here, we provide information on a PRD as the plausible option in obesity research not involving cancer, diabetes, glucotoxicity and lipotoxicity studies.Obesity was induced by exposing Drosophila melanogaster white mutant w1118 to four experimental diets for four weeks. Group 1 was fed regular food (control), group 2 was fed a 0.5% less yeast than in regular feed (PRD), group 3 was fed a 30% w/v sucrose to regular cornmeal food (HSD) and group 4 was fed a 10% w/v food-grade coconut oil to regular cornmeal food (HFD). Peristaltic waves were measured on 3rd instar larvae of all experimental groups. Negative geotaxis, fly survival, body mass, catalase activity, triglycerides (TG/TP), sterol, and total protein were measured in adult Drosophila melanogaster after four weeks.Triglycerides (TG/TP) and total protein levels were significantly higher in HSD phenotype. Sterols were higher in HFD phenotype. Though catalase enzyme activity was highest in PRD phenotype, this activity was not statistically significant when compared to that of HSD and HFD phenotypes. However, PRD phenotype had the lowest mass, highest survival rate and the highest negative geotaxis, thus demonstrating a balanced, stable and more viable metabolic status in the experimental model.A protein restricted diet induces a stable increased fat storage phenotype in Drosophila melanogaster.

Pretreatment of ellagic acid protects ifosfamide-induced acute nephrotoxicity in rat kidneys: A mitochondrial, histopathological and oxidative stress approaches

Abstract: Ifosfamide (IFO) kidney damage is an important organ toxicity in children and adults undergoing chemotherapy. Previous evidence has shown that IFO toxic metabolites such as acrolein and are associated with mitochondrial dysfunction, depletion of antioxidants, oxidative stress and may predispose the kidney to IFO toxicity. Bioactive food compounds such as ellagic acid (EA) found in fruits has been described as antioxidant and mitochondrial protective agents against toxicity-related mitochondrial damage and oxidative stress. In current study, the protective effects of EA on IFO-induced nephrotoxicity in male Wistar rats were investigated with histopathological, biochemical, and mitochondrial methods. The rats were randomly divided into four groups, control, IFO, IFO + EA, and EA groups. EA (25 mg/kg, i.p. daily) were administered to animals for 2 consecutive days and IFO (500 mg/kg, i.p.) was administered on third day. The results showed that pretreatment EA significantly increased mitochondrial succinate dehydrogenases (SDH) activity, and protected mitochondrial swelling, mitochondrial membrane potential (MMP), reactive oxygen species (ROS) formation, lipid peroxidation (LPO) and depletion glutathione (GSH). Histopathological findings demonstrated that EA had protective effects and reduced histopathological abnormalities caused by IFO. These results showed that EA administration protects the kidneys against mitochondrial dysfunction, oxidative stress and histopathological abnormality induced by IFO. Taken together, our results demonstrated that EA played a protective role against IFO-induced nephrotoxicity through mitochondrial protection and antioxidant properties.

Role of miRNAs in mediating organophosphate compounds induced toxicity

Abstract: Organophosphate compounds (OPCs) are a diverse class of chemicals utilized in both industrial and agricultural settings. The exact molecular pathways that OPCs-induced toxicity is caused by are still being investigated, despite the fact that studies on this topic have been ongoing for a long time. As a result, it's important to identify innovative strategies to uncover these processes and further the understanding of the pathways involved in OPCs-induced toxicity. In this context, determining the role of microRNAs (miRs) in the toxicity caused by OPCs should be taken into consideration. Recent research on the regulation function of miRs presents key discoveries to identify any gaps in the toxicity mechanisms of OPCs. As diagnostic indicators for toxicity in people exposed to OPCs, various expression miRs can also be used. The results of experimental and human studies into the expression profiles of miRs in OPCs-induced toxicity have been compiled in this article.