Neonatal exposure to ethinylestradiol increases ventral prostate growth and promotes epithelial hyperplasia and inflammation in adult male gerbils

The aim of this study was to analyse morphologically the ventral prostate of adult Mongolian gerbils exposed to ethinylestradiol (EE) during the first week of postnatal development. Lactating females received daily, by gavage, doses of 10 μg/kg of EE diluted in 100 μl of mineral oil from the 1st to 10th postnatal day of the pups (EE group). In the control group (C), the lactating females received only the vehicle. Upon completing 120 days of age, the male offspring were euthanized and the prostates collected for analyses. We employed morphological, stereological‐morphometrical, immunohistochemical and ultrastructural methods. The results showed that the postnatal exposure to EE doubled the prostatic complex weight, increasing the epithelial and stromal compartments, in addition to the secretory activity of the ventral lobe of the prostate. All glands exposed to EE showed strong stromal remodelling, and some foci of epithelial hyperplasia and inflammatory infiltrate in both luminal and epithelial or stromal compartments. Cells positive for anti‐AR and anti‐PCNA reactions increased into the epithelial and stromal tissues. ERα‐positive cells, which are normally found in the stromal compartment of intact prostates, were frequently observed in the prostatic epithelium of treated animals. This study demonstrated that the exposure to EE during postnatal development causes histophysiological alterations in this gland, predisposing to the development of prostatic lesions during life. These results are important for public health, considering that women worldwide have commonly used EE. Moreover, the bioaccumulation of this chemical has increased in different ecosystems.     

Sleep condition and cognitive decline in Japanese community‐dwelling older people: Data from a 4‐year longitudinal study

This study examined whether sleep duration and excessive daytime sleepiness (EDS) are related to cognitive decline among community‐dwelling older adults with intact cognition at baseline, using 4‐year longitudinal data. A total of 3,151 community‐dwelling older individuals aged ≥65 years were studied. They were assessed for cognitive function, including memory, attention, executive function and processing speed. Cognitive impairment was defined based on a score >1.5 standard deviations below the age‐ and education‐specific mean. Cognitive decline was defined in one or more cognitive tests at follow‐up. Self‐reported sleep duration (short, ≤6.0 hr; medium, 6.1–8.9 hr; long, ≥9.0 hr) and EDS at first‐wave examination were assessed and logistic regression analyses were used to examine the associations of sleep duration and EDS with cognitive status at second‐wave examination. The incidence of cognitive decline differed significantly among the sleep‐duration groups (short, 15.9%; medium, 11.9%; long, 20.1%; p = 0.001). The prevalence of having EDS was 13.1%, which was associated with a higher rate of cognitive decline than having no EDS (18.9% vs. 12.5%, p = 0.004). Long sleep duration compared with medium sleep duration (OR, 1.50; 95% CI, 1.05–2.13) and EDS (1.43; 1.01–2.03) independently impacted the incidence of cognitive decline. The results were similar after multiple imputations (long, 1.68, 1.12–2.52; EDS, 1.55, 1.05–2.29). In conclusion, our study revealed that both long sleep duration and EDS were independent risk factors associated with cognitive decline after 4 years among older adults.     

Fish pollutants MeHg and Aroclor cause permanent structural damage in male gonads and kidneys after prepubertal exposure

This study investigated whether or not prepubertal exposure to the fish contaminants methylmercury (MeHg) and the polychlorinated bisphenol Aroclor in low doses interferes with the histomorphometry of the testes, epididymis, liver and kidneys in rats. Wistar male rats, 21 days old, were allocated into the following: control (n = 17, received corn oil), MeHg (n = 17, received MeHg at 0.5 mg/kg/day), Aroclor (n = 17, received Aroclor at 1.0 mg/kg/day), low mix (n = 18, received MeHg at 0.05 mg/kg/day and Aroclor at 0.1 mg/kg/day), high mix (n = 18, received MeHg at 0.5 mg/kg/day and Aroclor at 1.0 mg/kg/day). Dosing continued from post natal day (PND) 23 to 53, by gavage. Euthanasia was performed on PND 53; or, after an interval of 62 days without exposure to chemicals, on PND 115. The degree of maturation of the seminiferous epithelium was delayed in chemical‐exposed groups and testicular interstitial oedema was observed at adulthood. The pattern of male gonad organization was changed in the Aroclor group on PND 53 and in all treated groups at adulthood. The animals from Aroclor, low mix and high mix groups showed a reduction in the number of Sertoli cells. Histological evidence of renal injury was observed in all chemical‐exposed groups in both ages. A probable target for MeHg and Aroclor in the reproductive system was Sertoli cells, in which possible dysfunctions could be linked to the other testicular alterations. Curiously, the main deleterious effects were late outcomes, along with the absence of synergistic interaction of MeHg and Aroclor in the parameters investigated. In conclusion, fish pollutants MeHg and Aroclor caused permanent structural damage in male gonads and kidneys after prepubertal exposure, without showing clear chemical interactions.     

Acute paraquat exposure determines dose‐dependent oxidative injury of multiple organs and metabolic dysfunction in rats: impact on exercise tolerance

This study investigated the pathological morphofunctional adaptations related to the imbalance of exercise tolerance triggered by paraquat (PQ) exposure in rats. The rats were randomized into four groups with eight animals each: (a) SAL (control): 0.5 ml of 0.9% NaCl solution; (b) PQ10: PQ 10 mg/kg; (c) PQ20: PQ 20 mg/kg; and (d) PQ30: PQ 30 mg/kg. Each group received a single injection of PQ. After 72 hours, the animals were subjected to an incremental aerobic running test until fatigue in order to determine exercise tolerance, blood glucose and lactate levels. After the next 24 h, lung, liver and skeletal muscle were collected for biometric, biochemical and morphological analyses. The animals exposed to PQ exhibited a significant anticipation of anaerobic metabolism during the incremental aerobic running test, a reduction in exercise tolerance and blood glucose levels as well as increased blood lactate levels during exercise compared to control animals. PQ exposure increased serum transaminase levels and reduced the glycogen contents in liver tissue and skeletal muscles. In the lung, the liver and the skeletal muscle, PQ exposure also increased the contents of malondialdehyde, protein carbonyl, 8‐hydroxy‐2′‐deoxyguanosine, superoxide dismutase and catalase, as well as a structural remodelling compared to the control group. All these changes were dose‐dependent. Reduced exercise tolerance after PQ exposure was potentially influenced by pathological remodelling of multiple organs, in which glycogen depletion in the liver and skeletal muscle and the imbalance of glucose metabolism coexist with the induction of lipid, protein and DNA oxidation, a destructive process not counteracted by the upregulation of endogenous antioxidant enzymes.     

Liver histology and ultrastructure of the Italian newt (Lissotriton italicus): Normal structure and modifications after acute exposure to nonylphenol ethoxylates

We examined, from a morphological and ultrastructural point of view, the liver of the Italian newt (Lissotriton italicus), under basal conditions and after exposure to nonylphenol ethoxylates (NPEs). Nonylphenol ethoxylates are surfactants widely used in a variety of industrial and agricultural processes that may pose a significant risk to aquatic fauna. NPEs, and their degradation intermediates, are known to affect reproductive biology acting as endocrine disruptors; besides estrogenic effects, nonylphenolic compounds may induce organ toxicity, particularly in liver and gonads. We investigated the effects of a nonylphenol ethoxylate (NPE10-ETO) on L. italicus liver using two low concentrations, consistent with the environmental concentrations. For this purpose, animals were exposed to nominal concentrations of 50 and 100 μg/L in a short-term experiment (96 h). A morpho-functional analysis was performed in order to investigate the amphibian responses to NPEs thus contributing to elucidate other potential mode of action of these compounds; indeed very little attention has been dedicated to amphibians though they are often exposed to such contaminants in aquatic ecosystems. Pathological alterations on liver histology and ultrastructure were observed at both tested concentrations; the main effects recorded were: increase of intercellular spaces, accumulation of large lipid droplets, increase in melanin content, and a degeneration phenomenon. We also detected, through confocal analysis, the induction of caspase-3, a key mediator of apoptosis, and an up-regulation of cytochrome P450-1A. By using both ultrastructural and a morpho-functional approach, we found that a short-term exposure to NPEs negatively affected the amphibian liver.     

Telomere measurement in individuals occupationally exposed to pesticide mixtures in tobacco fields

Occupational exposure to pesticides in tobacco fields causes genetic damage in farmers. The aim of this study was to analyze tobacco farmers chronically exposed to low doses of pesticides and nicotine (present in the tobacco leaves) in relation to absolute telomere length (aTL), and explore the influence of lifestyle characteristics, oxidative stress, and inorganic element levels. DNA was isolated from peripheral blood samples from agricultural workers and non‐exposed individuals, and aTL was measured by quantitative real time polymerase chain reaction (qPCR) analysis. Oxidative stress (thiobarbituric acid reactive substances [TBARS], which measures oxidative damage to lipids; and toxic equivalent antioxidant capacity [TEAC], which measures total equivalent antioxidant capacity) was evaluated in serum, and inorganic element content was analyzed in whole blood through particle‐induced X‐ray emission technique. It was found that exposure to pesticides and tobacco smoking had significant effects on aTL. Individuals occupationally exposed to complex mixtures of pesticides in tobacco fields and individuals who smoked had decreased aTL compared with the non‐exposed group. TBARS and TEAC were significantly elevated in the exposed group. There were no significant differences in inorganic elements. There was no evidence of an influence of age, gender, consumption of alcoholic beverages, or intake of fruits and vegetables on aTL within the groups. In addition, years of work in the tobacco field in the exposed group did not influence any of the variables analyzed. Although further studies were needed, these results suggested differences in telomere maintenance in tobacco farmers compared with the control group, indicating that telomere length may be a good biomarker of occupational exposure. Environ. Mol. Mutagen. 57:74–84, 2016. © 2015 Wiley Periodicals, Inc.     

Prenatal exposure to ethinylestradiol alters the morphologic patterns and increases the predisposition for prostatic lesions in male and female gerbils during ageing

Ethinylestradiol (EE) is an endocrine disruptor (ED) which acts as an oestrogen agonist; this compound is known as an oral contraceptive. Male and female rodents exposed to EE during critical time points of development, such as in the prenatal period, show alterations in their reproductive tract during adulthood. Few studies have placed an emphasis on the effects of EE during ageing. Thus, this study had as it's objective the analysis of the morphological and immunohistochemical effects of exposure to EE in the prenatal period on ventral male prostate and female prostate of gerbils (Meriones unguiculatus) during ageing. The animals were exposed to EE (15 μg/kg/day) during the 18–22th days of prenatal life (EE/PRE group), and the analyses were performed when the male and female reached 12 months of age. Our results showed an increase in the development of prostatic intraepithelial neoplasia (PIN), which was observed in the male and female prostate of EE/PRE groups. Immunohistochemistry showed a rise in prostatic epithelial and basal cells immunoreactivity, respectively, and to AR and p63 in the male EE/PRE. There were alterations in the morphological pattern of the prostatic glands and increase in predisposition to emergence of prostatic lesions of both sexes during ageing. Despite male and female having been exposed to the same doses of EE, the “exposure to EE promoted modifications” more accentuated in the male prostate. Thus the male gland is more sensitive to the action of this synthetic oestrogen than the female prostate.     

Oxidative damage in substantia nigra and striatum of rats chronically exposed to ozone

The purpose of this work was to study if chronic low-dose ozone exposure could per se induce oxidative damage to neurons of striatum and substantia nigra. Thirty male Wistar rats were divided into three groups--Group 1: exposed to an air stream free of ozone; Group 2: exposed for 15 days to ozone; Group 3: exposed for 30 days to ozone. Ozone exposure was carried out daily for 4 h at a 0.25 ppm dose. Each group was then tested for (1) motor activity, (2) quantification of lipid peroxidation levels, (3) Klüver-Barrera staining, and (4) immunohistochemistry for tyrosine hydroxylase (TH), dopamine and adenosine 3',5'-monophosphate-regulated phosphoprotein of 32 kD (DARPP-32), inducible nitric oxide synthase (iNOS), and superoxide dismutase (SOD), to study neuronal alterations in striatum and substantia nigra. Results indicate that ozone exposure causes a significant decrease in motor activity. Ozone produced lipid peroxidation, morphological alterations, loss of fibers and cell death of the dopaminergic neurons. The DARPP-32, iNOS and SOD expression increased with repetitive ozone exposure. These alterations suggest that ozone causes oxidative stress which induces oxidative damage to substantia nigra and striatum of the rat.     

DNA damage in Pakistani agricultural workers exposed to mixture of pesticides

A cross‐sectional study was designed to determine whether occupational exposure to a complex mixture of pesticides results in a significant increase of DNA damage in farmers chronically exposed to pesticides in open fields. Leukocytes from 47 agriculture workers exposed to pesticides and 50 controls were evaluated with comet assay. Workers recruitment was based on their exposure to pesticides during the spraying season on cotton crop. Serum from these individuals was also analyzed for pesticides presence using high performance liquid chromatography. Statistically significant difference (P < 0.001) in DNA damage of exposed individuals (mean ± S.D 14.80 ± 3.04 μm) was observed when compared with control group (6.54 ± 1.73 μm) as studied on the basis of comet tail length. Smokers had significantly higher mean comet tail length than nonsmokers and ex‐smokers in both workers (20.26 ± 3.53 vs. 14.19 ± 4.25, P < 0.001) and controls (7.86 ± 1.09 vs. 5.80 ± 1.59, P < 0.001), whereas age had a minimal effect on DNA damage (P < 0.05). The length of pesticide exposure is positively associated with DNA damage in exposed individuals (P < 0.001). Our study shows that chronic exposure to pesticides produces DNA damage in pesticide sprayers and suggests that this type of monitoring is recommended in preventive policies for pesticide sprayers. Environ. Mol. Mutagen., 2009. © 2008 Wiley‐Liss, Inc.     

Neonatal exposure to monosodium glutamate induces morphological alterations in suprachiasmatic nucleus of adult rat

Neonatal exposure to monosodium glutamate (MSG) induces circadian disorders in several physiological and behavioural processes regulated by the suprachiasmatic nucleus (SCN). The objective of this study was to evaluate the effects of neonatal exposure to MSG on locomotor activity, and on morphology, cellular density and expression of proteins, as evaluated by optical density (OD), of vasopressin (VP)‐, vasoactive intestinal polypeptide (VIP)‐ and glial fibrillary acidic protein (GFAP)‐immunoreactive cells in the SCN. Male Wistar rats were used: the MSG group was subcutaneously treated from 3 to 10 days of age with 3.5 mg/g/day. Locomotor activity was evaluated at 90 days of age using ‘open‐field’ test, and the brains were processed for immunohistochemical studies. MSG exposure induced a significant decrease in locomotor activity. VP‐ and VIP‐immunoreactive neuronal densities showed a significant decrease, while the somatic OD showed an increase. Major axes and somatic area were significantly increased in VIP neurons. The cellular and optical densities of GFAP‐immunoreactive sections of SCN were significantly increased. These results demonstrated that newborn exposure to MSG induced morphological alterations in SCN cells, an alteration that could be the basis for behavioural disorders observed in the animals.     

Pleurotus florida lectin normalizes duration dependent hepatic oxidative stress responses caused by arsenic in rat

Natural contamination of arsenic in ground water is a major health problem throughout the World. It is one of the most hazardous substances in the environment known to cause toxicity in multiple organs via oxidative stress. The molecular basis for arsenic toxicity involves direct or indirect damage to protein, lipid and DNA. Various studies have focused on the possible toxic effects of arsenic on membrane components and its correlation with oxidative damage. The present study was aimed to mitigation of arsenic induced hepatic oxidative stress by dietary modulation using of mushroom lectin in rats. Animals were divided into four groups; the first group was used as control. Groups 2, 3 and 4 were arsenic (20 ppm) exposed through drinking water, arsenic exposed plus oral ascorbic acid (25 mg/kg body weight) and arsenic exposed plus oral mushroom lectin (150 mg/kg body weight) respectively for a period of 12 weeks. We observed significant alterations in the antioxidant enzymes, oxidative stress intermediates and SOD₂ gene expression profile on arsenic exposure. These alterations were restored by co-administration of Pleurotus florida lectin which was as potent as standard antioxidant viz. ascorbic acid. The findings of the experiment suggested that P. florida lectin has capability of modulating arsenic mediated toxic effects and could be helpful in ameliorating them.     

Protective effect of date palm fruit extract (Phoenix dactylifera L.) on dimethoate induced-oxidative stress in rat liver

Nowadays, people’s exposure to chemical compounds such as organophosphorus insecticides is continuously on the rise more and more. Theses compounds have induced an excessive production of free radicals which are responsible for several cell alterations in the organism. Recent investigations have proved the crucial role of nutritional antioxidants to prevent the damage caused by toxic compounds. In this study, we investigate the role of date palm fruit extract (Phoenix dactylifera L.) in protection against oxidative damage and hepatotoxicity induced by subchronic exposure to dimethoate (20 mg/kg/day). Oral administration of dimethoate caused hepatotoxicity as monitored by the increase in the levels of hepatic markers enzymes (transaminases, alkaline phosphatase, gamma-glutamyl transferase and lactate dehydrogenase), as well as in hepatic malondialdehyde thus causing drastic alteration in antioxidant defence system. Particularly, the activities of superoxide dismutase (SOD) and glutathione peroxidase (GPx) were found increased by dimethoate while catalase (CAT) activity was reduced significantly. These biochemical alterations were accompanied by histological changes marked by appearance of vacuolization, necrosis, congestion, inflammation, and enlargement of sinusoids in liver section. Pretreatment with date palm fruit extract restored the liver damage induced by dimethoate, as revealed by inhibition of hepatic lipid peroxidation, amelioration of SOD, GPx and CAT activities and improvement of histopathology changes. The present findings indicate that in vivo date palm fruit may be useful for the prevention of oxidative stress induced hepatotoxicity.     

Whole genome sequencing and mutation rate analysis of trios with paternal dioxin exposure

2,3,7,8‐Tetrachlorodibenzo‐p‐dioxin (TCDD) or dioxin, is commonly considered the most toxic man‐made substance. Dioxin exposure impacts human health and diseases, birth defects and teratogenesis were frequently observed in children of persons who have been exposed to dioxin. However, the impact of dioxin on human mutation rate in trios has not yet been elucidated at the whole genome level. To identify and characterize the genetic alterations in the individuals exposed to dioxin, we performed whole genome sequencing (WGS) of nine Vietnamese trios whose fathers were exposed to dioxin. In total, 846 de novo point mutations, 26 de novo insertions and deletions, 4 de novo structural variations, and 1 de novo copy number variation were identified. The number of point mutations and dioxin concentrations were positively correlated (P‐value < 0.05). Considering the substitution pattern, the number of A > T/T > A mutation and the dioxin concentration was positively correlated (P‐value < 0.05). Our analysis also identified one possible disease‐related mutation in LAMA5 in one trio. These findings suggested that dioxin exposure might affect father genomes of trios leading to de novo mutations in their children. Further analysis with larger sample sizes would be required to better clarify mutation rates and substitution patterns in trios caused by dioxin.     

Metabolic alterations induced by chronic heat exposure in the rat: the involvement of thyroid function

The effects of chronic exposure to high environmental temperature (34°C) on T₄ production rate, foodintake, growth-rate and resting metabolic rate were investigated in adult male rats. This study was designed to examine the extent of variations and possible relationships between these parameters. As compared to control rats of the same body weight kept at 25°C, rats exposed to 34°C for 3–4 weeks exhibited a retarded growth-rate: 2.3 vs 4.0 g/day, a reduced food-intake: 15.2 vs 23.2 g/day, a decreased T₄ production-rate: 1.8 vs 2.7 g/day and a decreased oxygen consumption: 4.0 vs 5.4 ml/min. Heat-exposure altered the 4 parameters to a similar extent. T₄ supplementation (3 g/day) which induced a decrease in plasma TSH concentration, did not restore a normal growth-rate in heat-exposed rats. The decreased food-intake of the heat-exposed rats was not associated with any significant changes in the daily pattern of variations of liver glycogen content, or in the mean daily levels of blood glucose or insulin. The ratio T₃ to rT₃ in plasma was not altered by chronic heat exposure. When rats which had been chronically exposed to heat (25 days at 34°C) were exposed to 25°C, growth-rate, food-intake and oxygen consumption rapidly increased to control values whereas the rate of T₄ production remained low. It is concluded that (1) a decrease in thyroid hormone economy is not directly involved in the alterations of growth and energy expenditure in rats chronically exposed to heat, (2) heat exposure does not lead to the establishment of a fasted state resulting from a large reduction in voluntary food intake, (3) metabolic alterations induced by heat exposure are rapidly and completely reversible upon decreasing the environmental temperature.     

Aqueous extract of Terminalia arjuna prevents carbon tetrachloride induced hepatic and renal disorders

Background  

Carbon tetrachloride (CCl₄) is a well-known hepatotoxin and exposure to this chemical is known to induce oxidative stress and causes liver injury by the formation of free radicals. Acute and chronic renal damage are also very common pathophysiologic disturbances caused by CCl₄. The present study has been conducted to evaluate the protective role of the aqueous extract of the bark of Termnalia arjuna (TA), an important Indian medicinal plant widely used in the preparation of ayurvedic formulations, on CCl₄ induced oxidative stress and resultant dysfunction in the livers and kidneys of mice.     

DNA methylation alterations in response to pesticide exposure in vitro

Although pesticides are subject to extensive carcinogenicity testing before regulatory approval, pesticide exposure has repeatedly been associated with various cancers. This suggests that pesticides may cause cancer via nonmutagenicity mechanisms. The present study provides evidence to support the hypothesis that pesticide‐induced cancer may be mediated in part by epigenetic mechanisms. We examined whether exposure to seven commonly used pesticides (i.e., fonofos, parathion, terbufos, chlorpyrifos, diazinon, malathion, and phorate) induces DNA methylation alterations in vitro. We conducted genome‐wide DNA methylation analyses on DNA samples obtained from the human hematopoietic K562 cell line exposed to ethanol (control) and several organophosphate pesticides (OPs) using the Illumina Infinium HumanMethylation27 BeadChip. Bayesian‐adjusted t‐tests were used to identify differentially methylated gene promoter CpG sites. In this report, we present our results on three pesticides (fonofos, parathion, and terbufos) that clustered together based on principle component analysis and hierarchical clustering. These three pesticides induced similar methylation changes in the promoter regions of 712 genes, while also exhibiting their own OP‐specific methylation alterations. Functional analysis of methylation changes specific to each OP, or common to all three OPs, revealed that differential methylation was associated with numerous genes that are involved in carcinogenesis‐related processes. Our results provide experimental evidence that pesticides may modify gene promoter DNA methylation levels, suggesting that epigenetic mechanisms may contribute to pesticide‐induced carcinogenesis. Further studies in other cell types and human samples are required, as well as determining the impact of these methylation changes on gene expression. Environ. Mol. Mutagen. 2012. © 2012 Wiley Periodicals, Inc.     

Long‐lasting morphofunctional remodelling of liver parenchyma and stroma after a single exposure to low and moderate doses of cadmium in rats

Frequent exposure to cadmium (Cd) in low doses is common; however, the long‐lasting effects of this exposure are still poorly understood. Therefore in this study we have evaluated long‐lasting hepatic morphofunctional adaptations in rats exposed to low and moderate doses of Cd. Five experimental groups were tested: control (0.9% saline) and other four receiving single intraperitoneal doses of 0.67, 0.74, 0.86 and 1.1 mg of Cd/kg. The animals were killed after eight weeks and the following parameters were analysed: biometrics, oedema, Cd bio‐accumulation, collagen, glycogen, lipid droplets, superoxide dismutase (SOD) and catalase (CAT), serum transaminases, liver histopathology and stereology. In all groups exposed to Cd there was significant increase in SOD and CAT activities, ALP levels, proportion of binucleated hepatocytes, nuclei/cytoplasm ratio, macrophages (Kupffer cells) and collagen fibres. In these groups, glycogen accumulation by hepatocytes and the proportion of sinusoidal capillaries were significantly reduced compared with controls. The liver somatic index was increased, and liver oedema was evident in animals exposed to higher dose of Cd. Areas of necrosis were found in animals exposed to the three highest doses. These results indicate that Cd is an extremely toxic bioactive heavy metal, which even at low doses is able to disrupt liver homeostasis. At low and moderate doses, Cd exposure induces morphofunctional pathological remodelling of the hepatic stroma and parenchyma, which remain active after eight weeks. In response to injury, the liver tissue triggers a reactive process by enhancing activation of antioxidant enzymes and collagenogenesis.     

Resveratrol protects against inorganic arsenic-induced oxidative damage and cytoarchitectural alterations in female mouse hippocampus

Prolonged inorganic arsenic (iAs) exposure is widely associated with brain damage particularly in the hippocampus via oxidative and apoptotic pathways. Resveratrol (RES) has gained considerable attention because of its benefits to human health. However, its neuroprotective potential against iAs-induced toxicity in CA1 region of hippocampus remains unexplored.Therefore, we investigated the neuroprotective efficacy of RES against arsenic trioxide (As₂O₃)-induced adverse effects on neuronal morphology, apoptotic markers and oxidative stress parameters in mouse CA1 region (hippocampus).Adult female Swiss albino mice of reproductive maturity were orally exposed to either As₂O₃ (2 and 4 mg/kg bw) alone or in combination with RES (40 mg/kg bw) for a period of 45 days. After animal sacrifice on day 46, the perfusion fixed brain samples were used for the observation of neuronal morphology and studying the morphometric features. While the freshly dissected hippocampi were processed for biochemical estimation of oxidative stress markers and western blotting of apoptosis-associated proteins.Chronic iAs exposure led to significant decrease in Stratum Pyramidale layer thickness along with reduction in cell density and area of Pyramidal neurons in contrast to the controls. Biochemical analysis showed reduced hippocampal GSH content but no change in total nitrite (NO) levels following iAs exposure. Western blotting showed apparent changes in the expression levels of Bax and Bcl-2 proteins following iAs exposure, however the change was statistically insignificant. Contrastingly, iAs +RES co-treatment exhibited substantial reversal in morphological and biochemical observations.Together, these findings provide preliminary evidence of neuroprotective role of RES on structural and biochemical alterations pertaining to mouse hippocampus following chronic iAs exposure.     

Increased N7‐methyldeoxyguanosine DNA adducts after occupational exposure to pesticides and influence of genetic polymorphisms of paraoxonase‐1 and glutathione S‐transferase M1 and T1

There are concerns about genetic risks associated with long‐term exposure to pesticides as these compounds may damage DNA, resulting in mutations that eventually lead to cancer, neurological, and reproductive adverse health effects. This study assessed DNA damage in intensive agricultural workers exposed to pesticides by determining the levels of N7‐methyldeoxyguanosine (N7‐MedG), an adduct known to be a robust biomarker of recent exposure to chemical methylating agents. A cohort of 39 plastic greenhouse workers was assessed for changes in lymphocyte DNA N7‐MedG levels between low level and high level exposures during the course of a spraying season. The contributions of genetic polymorphisms of the pesticide‐metabolizing enzymes paraoxonase‐1 (PON1) and the glutathione S‐transferases, GSTM1 and GSTT1, on N7‐MedG levels and other potential confounders were also assessed. N7‐MedG increased in the period of high pesticide exposure as compared to the low exposure period (0.23 and 0.18 µmol N7‐MedG/mol dG for the unadjusted and adjusted linear mixed models, P = 0.02 and 0.08, respectively). Significant decreased levels of erythrocyte acetylcholinesterase and plasma cholinesterase were observed in the high versus low exposure period in both the unadjusted (2.85 U/g hemoglobin and 213.13 U/L, respectively) and adjusted linear mixed models (2.99 U/g hemoglobin and 230.77 U/L, respectively), indicating pesticide intake. In intensive agriculture workers, higher pesticide exposure increased DNA alkylation levels, further demonstrating the genotoxicity of pesticides in man. In addition, pesticide‐exposed individuals with inherited susceptible metabolic genotypes (particularly, null genotype for GSTM1 and the PON1 192R allele) appear to have an increased risk of genotoxic DNA damage. Environ. Mol. Mutagen. 56:437–445, 2015. © 2014 Wiley Periodicals, Inc.     

Foetal exposure to Panax ginseng extract reverts the effects of prenatal dexamethasone in the synthesis of testosterone by Leydig cells of the adult rat

The aim of this study was to examine the effect of maternal exposure to Panax ginseng extract (GE) on the prenatal dexamethasone (DEXA)‐induced increase in testosterone production by isolated Leydig cells in adult rats. Pregnant rats were treated with (i) GE (200 mg/kg) or vehicle on days 10–21; (ii) DEXA (100 μg/kg) or vehicle on days 14–21; or (iii) a combination of GE plus DEXA at the same doses and with the same regimen. Testosterone production was induced either by the activator of protein kinase A (dbcAMP) or substrates of steroidogenesis [22(R)‐hydroxycholesterol (22(R)‐OH‐C)] and pregnenolone. The capacity of rat Leydig cells exposed to DEXA to synthesize testosterone induced by dbcAMP, 22(R)‐OH‐C or pregnenolone was increased in comparison with the control group. Combined exposure to DEXA + GE prevented the effect of DEXA on the responsiveness of Leydig cells to all inductors of testosterone synthesis, whereas GE alone did not modify the response to inductors. No modifications in testosterone production were observed under basal conditions. StAR immunoexpression in Leydig cells was not modified by prenatal exposure to DEXA, GE or DEXA + GE. P450scc and glucocorticoid receptor immunoexpression was higher in offspring exposed to DEXA in comparison with the control group. This increased expression was prevented by combined treatment with DEXA + GE. The present findings demonstrate that GE is capable of reversing the effect of DEXA on testosterone synthesis by rat Leydig cells.