Human and Experimental Toxicology

Yilmaz, BO ;Yildizbayrak, N ;Aydin, Y ;Erkan, M

doi: 10.1177/0960327116686818pmid: 28067054

Acrylamide (AA) is a common chemical, produced during food processing and widely used in various industries and laboratory processes. Thus, AA causes a significant risk for human and animal health. Recently published studies have suggested that reproductive toxicity of AA and glycidamide (GA) was mainly due to the oxidative stress which can lead to cell apoptosis. The present experiment was conducted to investigate the effect of oxidative stress on the apoptosis of mouse Leydig (TM3) and Sertoli (TM4) cells induced by AA and its metabolite GA. TM3 and TM4 cells were exposed to AA (10 µM and 1 mM) and GA (1 µM and 0.5 mM) for 24 h. Following the exposure time, the Leydig and Sertoli cells were evaluated for measurement of cell viability, lactate dehydrogenase activity, lipid peroxidation and hydrogen peroxide levels, apoptosis/necrosis rate, and mRNA expression levels of apoptotic genes (caspase3, Bcl-2, Bax, and p53). The present study showed that AA and GA exposure caused decrease in cell viability and increase in excessive oxidative stress and apoptosis in both cell types. In conclusion, our in vitro results demonstrate that oxidative stress probably plays a major role in AA- and GA-induced apoptosis of Leydig and Sertoli cells.

Shen, H ;Liao, K ;Wu, H-F ;Lu, H-C ;Li, Y ;Li, Z ;Zhang, W

doi: 10.1177/0960327116685886pmid: 28067064

Objective: To investigate the effects of in utero exposure to high-dose di-n-butyl phthalate (DBP) on testicular cell apoptosis in late embryonic and pubertal male rat offspring. Methods: Twenty pregnant Sprague-Dawley (SD) rats were divided into two groups. During gestation day (GD) 12 to GD 19, control group was given 1 ml day−1 of olive oil and experimental group was given DBP 500 mg kg−1 day−1 by gavage. On GD 19.5 and postnatal day (PND) 45, the testes were removed. Morphological analysis of the testes was observed by transmission electron microscopy and hematoxylin and eosin (H&E) staining. Testicular cell apoptosis was detected by terminal deoxynucleotidyl transferase dUTP nick end labeling (TUNEL). The expression of Bcl-2, Bax, and p53 was presented by immunohistochemistry (IHC) and western blot. Data of the two groups was compared using independent samples t-test and Mann–Whitney test by SPSS 20.0. Results: H&E staining showed that spermatogenetic cells were significantly decreased in DBP exposed pubertal rat testis. The apoptosis index of testes in DBP-treated group was significantly lower on GD 19.5 but higher on PND 45 than that of the controls (p < 0.01). IHC and western blot revealed significantly increased expression of Bcl-2 in GD 19.5 rat testis and Bax and p53 in PND 45 rat testis after DBP exposure, compared with the control (p < 0.05). Conclusion: In utero exposure of high-dose DBP resulted in opposite effects on testicular cell apoptosis in late embryonic and pubertal rat offspring. The overexpression of Bcl-2, Bax, and p53 might be related to the occurrence of abnormal apoptosis and finally produce male infertility.

Satpute, RM ;Pawar, PP ;Puttewar, S ;Sawale, SD ;Ambhore, PD

doi: 10.1177/0960327116688070pmid: 28090784

Paraquat (PQ) is a nonselective bipyridyl herbicide widely used in agriculture to control weeds, but its accidental, occupational, or intentional exposure in humans is known to cause pneumo- and neurotoxicity which may proves fatal. Oxidative stress is reported as an underlined mechanism of PQ-induced toxicity in alveolar cells, neurons, and astroglia. PQ generates superoxides both through electron transport reaction (ETC) with nicotinamide adenine dinucleotide–dependent oxidoreductase and by the redox cycling via reaction with molecular oxygen. In lungs, it causes edema and inflammation resulting in neutrophils infiltration and subsequent activation of pro-inflammatory cytokines. In the present study, toxicity of subacute oral PQ exposure and effect of resveratrol (Res) and/or tetracycline (TC) on oxidative stress and inflammatory markers in lungs, brain, and liver was studied. Levels of glutathione and malondialdehyde and activities of myeloperoxidase, glutathione peroxidase, and catalase were measured in lungs, brain, and liver. PQ interferes in the function of mitochondrial ETC complexes causing decreased adenosine triphosphate levels, and hence the activities of complexes I and IV were studied in brain tissues. Res, a natural antioxidant, and TC, an antibiotic with its antimicrobial and anti-inflammatory properties, offered significant protection from severe oxidative stress and inflammation and ameliorated the general well-being of mice against the toxic outcome of PQ.

Qaid, EYA ;Zakaria, R ;Sulaiman, SF ;Yusof, NA Mohd ;Shafin, N ;Othman, Z ;Ahmad, AH ;Aziz, CB Abd

doi: 10.1177/0960327116689714pmid: 28111974

Impairment of memory is one of the most frequently reported symptoms during sudden hypoxia exposure in human. Cortical atrophy has been linked to the impaired memory function and is suggested to occur with chronic high-altitude exposure. However, the precise molecular mechanism(s) of hypoxia-induced memory impairment remains an enigma. In this work, we review hypoxia-induced learning and memory deficit in human and rat studies. Based on data from rat studies using different protocols of continuous hypoxia, we try to elicit potential mechanisms of hypobaric hypoxia–induced memory deficit.

Eldakroory, SA ;Morsi, DA El ;Abdel-Rahman, RH ;Roshdy, S ;Gouida, MS ;Khashaba, EO

doi: 10.1177/0960327116685887pmid: 28067071

Organochlorines (OCs) are common environmental pollutants that have been linked to cancer. This work aims to assess the role of OCs as a risk factor for breast cancer and to evaluate the cellular changes induced by exposure to such environmental contaminants. The study included 70 cancer patients subjected to thorough history taking and routine investigations. Samples from tumor and normal adjacent tissue were taken to measure OCs’ levels and to perform molecular analysis (some oncogenic and apoptotic markers) by flow cytometry. There were significantly higher concentrations of methoxychlor, dichloro-diphenyl-trichloroethane (DDT), hexa-chlorobenzene (HCB), and chlordane in tumor tissue samples compared to the surrounding normal tissue. There was a positive statistically significant correlation between G2m and dichloro-diphenyl-dichloroethane, DDT, and methoxychlor. There was also a negative correlation between propidium iodide (PI) and heptachlor as well as between PI, B-cell lymphoma 2, and methoxychlor. Annexin showed a negative correlation with HCB and methoxychlor. In conclusion, the higher level of organochlorine pesticides in the tissue specimens of breast cancer and the resultant molecular dysfunction highlight a possible association. Further research is warranted to elucidate the other possible mechanisms involved in the process of carcinogenesis.