Toxic Kidney Damage in Rats Following Subchronic Intraperitoneal Exposure to Element Oxide Nanoparticles.

Chronic diseases of the urogenital tract, such as bladder cancer, prostate cancer, reproductive disorders, and nephropathies, can develop under the effects of chemical hazards in the working environment. In this respect, nanosized particles generated as by-products in many industrial processes seem to be particularly dangerous to organs such as the testes and the kidneys. Nephrotoxicity of element oxide particles has been studied in animal experiments with repeated intraperitoneal injections of Al2O3, TiO2, SiO2, PbO, CdO, CuO, and SeO nanoparticles (NPs) in total doses ranging from 4.5 to 45 mg/kg body weight of rats. NPs were synthesized by laser ablation. After cessation of exposure, we measured kidney weight and analyzed selected biochemical parameters in blood and urine, characterizing the state of the excretory system. We also examined histological sections of kidneys and estimated proportions of different cells in imprint smears of this organ. All element oxide NPs under investigation demonstrated a nephrotoxic effect following subchronic exposure. Following the exposure to SeO and SiO2 NPs, we observed a decrease in serum creatinine and urea, respectively. Exposure to Al2O3 NPs caused an increase in urinary creatinine and urea, while changes in total protein were controversial, as it increased under the effect of Al2O3 NPs and was reduced after exposure to CuO NPs. Histomorphological changes in kidneys are associated with desquamation of the epithelium (following the exposure to all NPs except those of Al2O3 and SiO2) and loss of the brush border (following the exposure to all NPs, except those of Al2O3, TiO2, and SiO2). The cytomorphological evaluation showed greater destruction of proximal sections of renal tubules. Compared to the controls, we observed statistically significant alterations in 42.1% (8 of 19) of parameters following the exposure to PbO, CuO, and SeO NPs in 21.1% (4 of 19)-following that, to CdO and Al2O3 NPs-and in 15.8% (3 of 19) and 10.5% (2 of 19) of indicators, following the exposure to TiO2 and SiO2 nanoparticles, respectively. Histomorphological changes in kidneys are associated with desquamation of epithelium and loss of the brush border. The cytomorphological evaluation showed greater destruction of proximal sections of renal tubules. The severity of cyto- and histological structural changes in kidneys depends on the chemical nature of NPs. These alterations are not always consistent with biochemical ones, thus impeding early clinical diagnosis of renal damage. Unambiguous ranking of the NPs examined by the degree of their nephrotoxicity is difficult. Additional studies are necessary to establish key indicators of the nephrotoxic effect, which can facilitate early diagnosis of occupational and nonoccupational nephropathies.

Nanoaggregates of Biphilic Carboxyl-Containing Copolymers as Carriers for Ionically Bound Doxorubicin.

Application of nanocarriers for drug delivery brings numerous advantages, allowing both minimization of side effects common in systemic drug delivery and improvement in targeting, which has made it the focal point of nanoscience for a number of years. While most of the studies are focused on encapsulation of hydrophobic drugs, delivery of hydrophilic compounds is typically performed via covalent attachment, which often requires chemical modification of the drug and limits the release kinetics. In this paper, we report synthesis of biphilic copolymers of various compositions capable of self-assembly in water with the formation of nanoparticles and suitable for ionic binding of the common anticancer drug doxorubicin. The copolymers are synthesized by radical copolymerization of N-vinyl-2-pyrrolidone and acrylic acid using n-octadecyl-mercaptan as a chain transfer agent. With an increase of the carboxyl group's share in the chain, the role of the electrostatic stabilization factor of the nanoparticles increased as well as the ability of doxorubicin as an ion binder. A mathematical description of the kinetics of doxorubicin binding and release is given and thermodynamic functions for the equilibrium ionic binding of doxorubicin are calculated.

The sesquiterpenoid valerenic acid protects neuronal cells from the detrimental effects of the fungicide benomyl on apoptosis and DNA oxidation.

BACKGROUND: Valerenic acid (VA), a sesquiterpenoid of the plant Valeriana officinalis, has attracted attention of the research community due to its potential positive role against neurodegenerative diseases induced by chemicals. However, the relevant evidence in the literature is scarce. Therefore, this study aimed to examine the putative protective role of VA on the toxic effects of the fungicide benomyl on SH-SY5Y neural cells. METHODS: Cell viability was determined via the MTT and NRU assays, DNA damage was assessed via comet assay and apoptosis was evaluated through the expression of relevant genes. RESULTS: According to the results, exposure of the cells to benomyl enhanced viability inhibition and promoted DNA damage and apoptosis since the expression levels of the genes coding for MAPK8, NF-kB, Bax, Caspase-9 and Caspase-3 were increased. Treatment of the cells with VA ameliorated these effects in a concentration dependent manner. CONCLUSION: It is concluded that the molecular mechanism through which benomyl exerts its toxic action appears to depend on DNA oxidation and apoptosis induction. Furthermore, VA, a plant-derived compound is a protective antioxidant against pesticide-induced toxicity. Therefore, herbs, extracts and compounds of plant origin could be used as nutritional supplements that back up the beneficial role of medicine in neurodegenerative diseases.

Ameliorative Effects of the Sesquiterpenoid Valerenic Acid on Oxidative Stress Induced in HepG2 Cells after Exposure to the Fungicide Benomyl.

Valerenic acid (VA) is a sesquiterpenoid and a phytoconstituent of the plant valerian used for sleeping disorders and anxiety. The frequency of using herbal components as therapeutic nutritional agents has increased lately. Their ability to improve redox homeostasis makes them a valuable approach against harmful xenobiotics. The purpose of this study was to evaluate the putative beneficial role of VA against the redox-perturbating role of the fungicide benomyl in HepG2 human liver cells in terms of oxidative stress in the cellular environment and in endoplasmic reticulum (ER). Benomyl increased cell total oxidant status and reactive oxygen species production and decreased total antioxidant status. The expression of genes coding for antioxidant molecules, namely, heme oxygenase-1, alpha glutathione s-transferase, NF-ĸB, and liver fatty acid binding protein, were decreased due to benomyl. VA ameliorated these effects. Benomyl also increased ER-stress-related molecules such as endoplasmic reticulum to nucleus signaling 1 protein, glucose-regulated protein 78, and caspase-12 levels, and VA acted also as a preventive agent. These results indicate that VA exerts ameliorative effects after benomyl-induced oxidative stress. VA, a widely used nutritional supplement, is a compound with potent antioxidant properties, which are valuable for the protection of cells against xenobiotic-induced oxidative damage.

The state of the scientific revolution in toxicology.

Science changes in waves, the so-called paradigm shifts or scientific revolutions. This concept was prominently elabo­rated by Thomas S. Kuhn more than 50 years ago in what remains one of the most cited science philosophy books of all time. Kuhn described how "normal science" experiences anomalies, which bring it to crisis and revolution from which a new, immature scientific paradigm results, which over time becomes the new normal. Building on an analysis on how this applies to toxicology and its change in approach in 2008, we concluded at the time that toxicology had encountered a number of such anomalies and was moving into crisis. Here, the progress along Kuhn's trajectory over the last 12 years of a scientific revolution is discussed. We conclude that this decade has shown up even more anomalies, and the perception of crisis has spread and consolidated. Indications of revolutionary paradigm changes are emerging.

Biochemical adaptation of wild and cultivated soybean against toxicity of lead salts.

Agricultural production is becoming increasingly dependent on the environmental factors that alter soil properties, plant productivity, and product quality. Environment pollution caused by heavy metals because of human activities are among the most dangerous pollutants on the biosphere. Here, we have studied the biochemical adaptation of wild and cultivated soybeans to the simulated effects of lead nitrate and lead acetate. Lead in the form of acetate had a relevant toxic effect, as evidenced by a significant increase in the concentration of malonic dialdehyde in the treated samples relative to control samples. Catalase and peroxidase, possibly performing a signaling function, are involved in the adaptation to the toxicity of Pb salts. The studied Pb salts showed a predominant stimulating effect on the specific activity of acid phosphatases in cultivated soybean, while the ribonuclease activity changed in both Glycine species. Moreover, in wild soybean, it was mostly suppressive, except for the first day. We found that the electrophoretic spectra of acid phosphatases of soybean seedlings was highly stabile, while that of ribonucleases varied depending on the salt. On the seventh day of exposure, lead nitrate caused a decrease in the specific activity of the studied hydrolases of seedlings of cultivated and wild soybeans. A change in the number or electrophoretic mobility of multiple forms of enzymes during treatment with Pb salts was revealed, which indicates the adaptation of the plants at the molecular genetic level. These results imply that the observed enzymes can be used as sensitive indicators for predicting the effects of heavy metals on soybean.

Benomyl, a benzimidazole fungicide, induces oxidative stress and apoptosis in neural cells.

Fungicides are used in the agricultural sector against the harmful action of fungi, however they are potential toxic agents for the environment and the living organisms. Benomyl is a widely encountered benzimidazole fungicide that exerts its toxicity via inhibiting microtubule formation in the nervous system and the male reproductive and endocrine systems, whilst it is a known teratogen. Since toxic effects of benomyl and its molecular mechanisms are not fully understood, we aimed to detect its neurotoxic potential via evaluating cytotoxicity, oxidative stress and apoptosis in SH-SY5Y cell line. The cells were incubated with benomyl in a concentration range between 1 and 6 µM for 24 h. Our results indicated a concentration-dependent enhancement of reactive oxygen species measured through flow cytometry and DNA damage evaluated via the comet assay. Additionally, it induced apoptosis in all tested concentrations. According to the findings of the present study, benomyl is a xenobiotic, which it appears to exert its toxic action via a redox-related mechanism that, finally, induces cell apoptosis and death. We believe that this study will offer further insight in the toxicity mechanism of benomyl, although further studies are recommended in order to elucidate these mechanisms in the molecular level.

Analysis of HCRTR2, GNB3, and ADH4 Gene Polymorphisms in a Southeastern European Caucasian Cluster Headache Population.

Studies point to an increased hereditary risk of cluster headache. HCRTR2 gene rs2653349 and ADH4 gene rs1800759 polymorphisms have been associated with cluster headache susceptibility. Also, GNB3 rs5443 polymorphism, associated with increased signal transduction via GPCRs, seems to influence triptan treatment response. DNA from 114 cluster headache patients and 570 non-related controls, representing a general Southeastern European Caucasian (SEC) population, was extracted from buccal swabs and genotyped using real-time PCR. Gene distribution for the rs2653349 was GG = 79.8%, GA = 18.4%, and AA = 1.8% for patients and GG = 79.1%, GA = 19.1%, and AA = 1.8% for controls. The frequency of the mutated A allele was 11.0% for patients and 11.3% for controls. The frequencies for rs5443 were CC = 44.7%, CT = 44.7%, and TT = 10.5% for patients and CC = 43.9%, CT = 42.6%, and TT = 13.5% for controls. The frequency of the mutated T allele was 32.9% for patients and 34.8% for controls. A 2.7-fold more frequent appearance of the mutated T allele was observed in patients with better triptan treatment response, although not statistically significant. For rs1800759, the frequencies were CC = 36.0%, CA = 43.0%, and AA = 21.0% for patients and CC = 34.0%, CA = 50.2%, and AA = 15.8% for controls. The frequency of the mutated A allele was 42.5% and 40.9% for patients and controls, respectively. The mutated T allele of GNB3 rs5443 polymorphism was more prevalent in patients with better triptan treatment response, indicating a possible trend of association between this polymorphism and triptan treatment response in SEC population. According to our observation, no association of HCRTR2 rs2653349 and ADH4 rs1800759 polymorphisms and cluster headache in SEC population could be documented.

Transgenic crops for the agricultural improvement in Pakistan: a perspective of environmental stresses and the current status of genetically modified crops.

Transgenic technologies have emerged as a powerful tool for crop improvement in terms of yield, quality, and quantity in many countries of the world. However, concerns also exist about the possible risks involved in transgenic crop cultivation. In this review, literature is analyzed to gauge the real intensity of the issues caused by environmental stresses in Pakistan. In addition, the research work on genetically modified organisms (GMOs) development and their performance is analyzed to serve as a guide for the scientists to help them select useful genes for crop transformation in Pakistan. The funding of GMOs research in Pakistan shows that it does not follow the global trend. We also present socio-economic impact of GM crops and political dimensions in the seed sector and the policies of the government. We envisage that this review provides guidelines for public and private sectors as well as the policy makers in Pakistan and in other countries that face similar environmental threats posed by the changing climate.

A review of the alleged health hazards of monosodium glutamate.

Monosodium glutamate (MSG) is an umami substance widely used as flavor enhancer. Although it is generally recognized as being safe by food safety regulatory agencies, several studies have questioned its long-term safety. The purpose of this review was to survey the available literature on preclinical studies and clinical trials regarding the alleged adverse effects of MSG. Here, we aim to provide a comprehensive overview of the reported possible risks that may potentially arise following chronic exposure. Furthermore, we intend to critically evaluate the relevance of this data for dietary human intake. Preclinical studies have associated MSG administration with cardiotoxicity, hepatotoxicity, neurotoxicity, low-grade inflammation, metabolic disarray and premalignant alterations, along with behavioral changes. Moreover, links between MSG consumption and tumorigenesis, increased oxidative stress and apoptosis in thymocytes, as well as genotoxic effects in lymphocytes have been reported. However, in reviewing the available literature, we detected several methodological flaws, which led us to conclude that these studies have limited relevance for extrapolation to dietary human intakes of MSG risk exposure. Clinical trials have focused mainly on the effects of MSG on food intake and energy expenditure. Besides its well-known impact on food palatability, MSG enhances salivary secretion and interferes with carbohydrate metabolism, while the impact on satiety and post-meal recovery of hunger varied in relation to meal composition. Reports on MSG hypersensitivity, also known as 'Chinese restaurant syndrome', or links of its use to increased pain sensitivity and atopic dermatitis were found to have little supporting evidence. Based on the available literature, we conclude that further clinical and epidemiological studies are needed, with an appropriate design, accounting for both added and naturally occurring dietary MSG. Critical analysis of existing literature, establishes that many of the reported negative health effects of MSG have little relevance for chronic human exposure and are poorly informative as they are based on excessive dosing that does not meet with levels normally consumed in food products.

Estimation of daily intake and risk assessment of organophosphorus pesticides based on biomonitoring data - The internal exposure approach.

Human exposure to pesticides can be estimated through different approaches. The approach adopted in this study is based on internal dose measures. Studies published during 2001 and 2017 were collected from PubMed and Scopus databases, filtered and organized. The intake of parent compounds is estimated based on the urinary excretion of different OP metabolites applying a mathematical model previously used for similar purposes. Once defined an Estimated Daily Intake (EDI), risk assessment is performed through comparison with specific guideline values and hazard index (HI) is calculated to assess cumulative health risk. The EDI was expressed as malathion, diazinon, parathion, phorate and dimethoate equivalents. Differences in exposure between pregnant women, general population, children and farmers are highlighted and exposures are presented by country and sampling year. Higher exposure to OPs was calculated for farmers, followed by children whereas pregnant women were less exposed. Median HQ values for children ranged between 0.016 and 0.618, for pregnant women 0.005-0.151, for general population 0.008-0.206 and for farmers 0.009-0.979. Combined exposure to dimethoate and phorate was the worst-case scenario. The annual distribution of the urinary DAPs showed that exposure to OPs since 1998 tends to be stable for both children and adults.

Addressing concerns over the fate of DNA derived from genetically modified food in the human body: A review.

Global commercialization of GM food and feed has stimulated much debate over the fate of GM food-derived DNA in the body of the consumer and as to whether it poses any health risks. We reviewed the fate of DNA derived from GM food in the human body. During mechanical/chemical processing, integrity of DNA is compromised. Food-DNA can survive harsh processing and digestive conditions with fragments up to a few hundred bp detectable in the gastrointestinal tract. Compelling evidence supported the presence of food (also GM food) derived DNA in the blood and tissues of human/animal. There is limited evidence of food-born DNA integrating into the genome of the consumer and of horizontal transfer of GM crop DNA into gut-bacteria. We find no evidence that transgenes in GM crop-derived foods have a greater propensity for uptake and integration than the host DNA of the plant-food. We found no evidence of plant-food DNA function/expression following transfer to either the gut-bacteria or somatic cells. Strong evidence suggested that plant-food-miRNAs can survive digestion, enter the body and affect gene expression patterns. We envisage that this multi-dimensional review will address questions regarding the fate of GM food-derived DNA and gene-regulatory-RNA in the human body.

Antimicrobial resistance in bacterial pathogens among hospitalised patients with severe invasive infections.

The most severe infections are invasive infections, due to the fact that the germs can accumulate in multiple sites and produce a body-wide infection known as sepsis. Septic shock has the highest mortality rate among non-traumatic medical conditions. In this study, we aimed to evaluate the incidence and prevalence of invasive infections in a hospital environment. Another second objective was to establish the aetiology of invasive infections in our hospital and the antibiotic resistance profile of the germs involved, which are both important for determining the therapeutic approach for the treatment of these infections. The study included 505 hospitalized patients from which we collected a total of 974 blood cultures. For the analysis of the blood cultures, we used an automated incubator. The bottles flagged as positive were subcultured on blood agar, and the grown colonies were identified using an identification system. Invasive infections had a prevalence rate of 27.72% in our hospital. From the 974 blood cultures, we isolated 170 bacterial strains: Staphylococcus aureus (SA; 63 strains, 37.06%), Klebsiella spp. (27 strains, 15.88%), coagulase-negative staphylococci (CoNS; 18 strains, 10.59%), Enterococcus spp. (17 strains, 10.00%), Escherichia coli (12 strains, 7.06%), Streptococcus spp. (11 strains, 6.47%) and other bacterial species. The prevalence of methicillin-resistant SA (MRSA) in our study was 36.51% from the SA strains. The MRSA prevalence differed significantly according to age (37.50% in adults vs. 28.57% in children, P=0.047) and ICU admission (42.42% in ICU patients vs. 30.00% in non-ICU patients, P=0.018). We performed a multivariate analysis of the invasive infection risk which detected as significant predictors the admission into the cardiology ward and plastic surgery ward. On the whole, the findings of this study indicate that the high prevalence of Gram-positive cocci in blood cultures, mostly SA, with multidrug resistance has important consequences for the management of invasive infections.

Antioxidant effects of an olive oil total polyphenolic fraction from a Greek Olea europaea variety in different cell cultures.

BACKGROUND: Numerous studies have been carried out concerning the advantageous health effects, especially the antioxidant effects, of olive oil's (OO) individual biophenolic compounds, but none until now for its total phenolic fraction (TPF). Plenty of evidence, in research about nutrition and healthiness, points out that it is the complex mixture of nutritional polyphenols, more than each compound separate, which can synergistically act towards a health result. PURPOSE: The aim of the present study was to examine the antioxidant properties of an extra virgin olive oil (EVOO) total polyphenolic fraction, from a Greek endemic variety of Olea europaea in cell lines. METHODS: EVOO from a Greek endemic variety was used for the extraction of a total polyphenolic fraction, using a green CPE­based method. The redox status [in terms of ROS, GSH, TBARS, protein carbonyls] was assessed at a cellular level, particularly in EA.hy926 endothelial, HeLa, HepG2 hepatic cells and C2C12 myoblasts. Moreover, the levels of glutamate-cysteine ligase catalytic subunit (γ-GCLc) of GSH, one of the most important antioxidant enzymes, were assessed by western blot. RESULTS: According to the results, TPF improves the redox profile of all cell lines, mainly by increasing GSH and its catalytic subunit, while at low, not cytotoxic TPF concentrations there was a decrease in TBARS and carbonyls. Regarding ROS levels a reduction was observed only in the HepG2 cell line, contrary to the other cell lines, that there is no statistically significant difference. CONCLUSION: The TPF appeared to protect cells from oxidative stress due to the strong antioxidant activity of its polyphenols. This could have interesting implications in development of new products based on this olive oil to provide protection and treatment against harmful effects of free radicals.

Oxidative Stress in Methylmercury-Induced Cell Toxicity.

Methylmercury (MeHg) is a hazardous environmental pollutant, which elicits significant toxicity in humans. The accumulation of MeHg through the daily consumption of large predatory fish poses potential health risks, and the central nervous system (CNS) is the primary target of toxicity. Despite well-described neurobehavioral effects (i.e., motor impairment), the mechanisms of MeHg-induced toxicity are not completely understood. However, several lines of evidence point out the oxidative stress as an important molecular mechanism in MeHg-induced intoxication. Indeed, MeHg is a soft electrophile that preferentially interacts with nucleophilic groups (mainly thiols and selenols) from proteins and low-molecular-weight molecules. Such interaction contributes to the occurrence of oxidative stress, which can produce damage by several interacting mechanisms, impairing the function of various molecules (i.e., proteins, lipids, and nucleic acids), potentially resulting in modulation of different cellular signal transduction pathways. This review summarizes the general aspects regarding the interaction between MeHg with regulators of the antioxidant response system that are rich in thiol and selenol groups such as glutathione (GSH), and the selenoenzymes thioredoxin reductase (TrxR) and glutathione peroxidase (Gpx). A particular attention is directed towards the role of the PI3K/Akt signaling pathway and the nuclear transcription factor NF-E2-related factor 2 (Nrf2) in MeHg-induced redox imbalance.

Correction to: Population-Based Analysis of Cluster Headache-Associated Genetic Polymorphisms.

The original version of this article unfortunately contained mistakes in author group section.

Population-Based Analysis of Cluster Headache-Associated Genetic Polymorphisms.

Cluster headache is a disorder with increased hereditary risk. Associations between cluster headache and polymorphism rs2653349 of the HCRTR2 gene have been demonstrated. The less common allele (A) seems to reduce disease susceptibility. The polymorphism rs5443 of the GNB3 gene positively influences triptan treatment response. Carriers of the mutated T allele are more likely to respond positively compared to C:C homozygotes, when treated with triptans. DNA was extracted from buccal swabs obtained from 636 non-related Southeastern European Caucasian individuals and was analyzed by real-time PCR. Gene distribution for the rs2653349 was G:G = 79.1%, G:A = 19.2%, and A:A = 1.7%. The frequency of the wild-type G allele was 88.7%. The frequencies for rs5443 were C:C = 44.0%, C:T = 42.6%, and T:T = 13.4%. The frequency of the wild-type C allele was 65.3%. The frequency distribution of rs2653349 in the Southeastern European Caucasian population differs significantly when compared with other European and East Asian populations, and the frequency distribution of rs5443 showed a statistically significant difference between Southeastern European Caucasian and African, South Asian, and East Asian populations. For rs2653349, a marginal statistically significant difference between genders was found (p = 0.080) for A:A versus G:G and G:A genotypes (OR = 2.78), indicating a higher representation of male homozygotes for the protective mutant A:A allele than female. No statistically significant difference was observed between genders for rs5443. Cluster headache pathophysiology and pharmacotherapy response may be affected by genetic factors, indicating the significant role of genotyping in the overall treatment effectiveness of cluster headaches.

Physiological and anthocyanin biosynthesis genes response induced by vanadium stress in mustard genotypes with distinct photosynthetic activity.

The present study aimed to elucidate the photosynthetic performance, antioxidant enzyme activities, anthocyanin contents, anthocyanin biosynthetic gene expression, and vanadium uptake in mustard genotypes (purple and green) that differ in photosynthetic capacity under vanadium stress. The results indicated that vanadium significantly reduced photosynthetic activity in both genotypes. The activities of the antioxidant enzymes were increased significantly in response to vanadium in both genotypes, although the purple exhibited higher. The anthocyanin contents were also reduced under vanadium stress. The anthocyanin biosynthetic genes were highly expressed in the purple genotype, notably the genes TT8, F3H, and MYBL2 under vanadium stress. The results indicate that induction of TT8, F3H, and MYBL2 genes was associated with upregulation of the biosynthetic genes required for higher anthocyanin biosynthesis in purple compared with the green mustard. The roots accumulated higher vanadium than shoots in both mustard genotypes. The results indicate that the purple mustard had higher vanadium tolerance.

Risk assessment of exposure to aflatoxin B1 and ochratoxin A through consumption of different Pistachio (Pistacia vera L.) cultivars collected from four geographical regions of Iran.

Iran is one of the main suppliers of pistachio for the European market accounting for over 90% of its demands; hence, efficient analytical methods are required for detection of mycotoxins contamination in pistachio kernels before exporting them. In this study, aflatoxin B1 (AFB1) and ochratoxin A (OTA) levels in five pistachio cultivars collected from four sites of Iran, were measured by HPLC. Based on the results, risk assessment for AFB1 and OTA residues was done. The highest mean concentrations of AFB1 and OTA were found in Ahmad-aghaei (4.33 and 2.19 ng/g, respectively) and Akbari (4.08 and 1.943 ng/g, respectively) cultivars from Rafsanjan, Iran. Even the highest concentrations of AFB1 and OTA in analyzed samples were lower than the corresponding maximum limits set by EU authorities. The hazard index (HI) value for consumers of Iranian pistachio is below one. It could be concluded that consumption of pistachio cultivated in these regions poses no health risk of mycotoxins exposure.

Stanozolol administration combined with exercise leads to decreased telomerase activity possibly associated with liver aging.

Anabolic agents are doping substances which are commonly used in sports. Stanozolol, a 17α­alkylated derivative of testosterone, has a widespread use among athletes and bodybuilders. Several medical and behavioral adverse effects are associated with anabolic androgenic steroids (AAS) abuse, while the liver remains the most well recognized target organ. In the present study, the hepatic effects of stanozolol administration in rats at high doses resembling those used for doping purposes were investigated, in the presence or absence of exercise. Stanozolol and its metabolites, 16­ß­hydroxystanozolol and 3'­hydroxystanozolol, were detected in rat livers using liquid chromatography­mass spectrometry (LC­MS). Telomerase activity, which is involved in cellular aging and tumorigenesis, was detected by examining telomerase reverse transcriptase (TERT) and phosphatase and tensin homolog (PTEN) expression levels in the livers of stanozolol­treated rats. Stanozolol induced telomerase activity at the molecular level in the liver tissue of rats and exercise reversed this induction, reflecting possible premature liver tissue aging. PTEN gene expression in the rat livers was practically unaffected either by exercise or by stanozolol administration.