Tebuconazole induced cytotoxic and genotoxic effects in HCT116 cells through ROS generation.

Tebuconazole (TEB) is a common triazole fungicide that has been widely used for the control of plant pathogenic fungi, suggesting that mammal exposure occurs regularly. Several studies demonstrated that TEB exposure has been linked to a variety of toxic effects, including neurotoxicity, immunotoxicity, reprotoxicity and carcinogenicity. However, there is a few available data regarding the molecular mechanism involved in TEB-induced toxicity. The current study was undertaken to investigate the toxic effects of TEB in HCT116 cells. Our results showed that TEB caused cytotoxicity by inhibiting cell viability as assessed by the MTT assay. Furthermore, we have demonstrated that TEB induced a significant increase in the reactive oxygen species (ROS) production leading to the induction of lipid peroxidation and DNA fragmentation and increased superoxide dismutase (SOD) and catalase (CAT) activities. Moreover, TEB exposure induced mitochondrial membrane potential loss and caspase-9/-3 activation. Treatment with general caspases inhibitor (Z-VAD-fmk) significantly prevented the TEB-induced cell death, indicating that TEB induced caspases-dependent cell death. These findings suggest the involvement of oxidative stress and apoptosis in TEB-induced toxicity in HCT116.

Tebuconazole induced oxidative stress and histopathological alterations in adult rat heart.

TEB belongs to the family of triazole fungicides and it is used to protect agricultural crop plants from fungal pathogens. The information regarding its cardiotoxic effects through different pathways particularly by perturbing the oxidative balance and causing damage to the myocardium is still limited. In the present study, oxidative and histopathologic damages caused by TEB in the cardiac tissue of male adult rats, were evaluated. Rats were exposed orally to TEB at 0.9, 9, 27 and 45 mg/kg b.w. for 28 days. Results showed that following TEB treatment malondialdehyde (MDA), protein carbonyl (PC), advanced oxidation protein product (AOPP), antioxidant enzyme activities (GPx and GR) and GSSG levels increased, while GSH levels and thus the GSH/GSSG ratio decreased. Superoxide dismutase (SOD) and catalase (CAT) initially increased at the doses of 0.9, 9 and 27 mg/kg b.w. and then decreased at the dose of 45 mg/kg b.w. Moreover, western blot analysis showed that TEB increased SOD1, CAT and HSP70 protein levels after 24 h. Furthermore, TEB induced various histological changes in the myocardium, including leucocytic infiltration, hemorrhage congestion of cardiac blood vessels and cytoplasmic vacuolization. Therefore, our investigation revealed, that TEB exhibits cardiotoxic effects by changing oxidative balance and damaging the cardiac tissue.

Oxidative stress, DNA damage and apoptosis induced by tebuconazole in the kidney of male Wistar rat.

Tebuconazole (TEB) is a broad-spectrum conazole fungicide that has been used in agriculture in the control of foliar and soil-borne diseases of many crops. The present study has investigated the adverse effects of subchronic exposure to TEB on the kidney of male rats. Animals were divided into four equal groups and treated with TEB at increasing doses 0.9, 9 and 27 mg/kg body weight for 28 consecutive days. The results showed that TEB induced oxidative stress in the kidney demonstrated by an increase in malondialdehyde (MDA), protein carbonyl (PC), advanced oxidation protein product (AOPP) levels and DNA damage, as compared to the controls. Furthermore, superoxide dismutase (SOD), catalase (CAT), glutathione peroxidase (GPx) activities were increased in the renal tissue of treated rats. Moreover, significant decrease in reduced glutathione (GSH) content in TEB-treated rats was observed, while oxidized glutathione (GSSG) levels were increased, thus a marked fall in GSH/GSSG ratio was registered in the kidney. Glutathione reductase (GR) activity showed a significant increase after TEB exposure. Moreover, TEB down-regulated the expression of Bcl2 and up-regulated the expression of Bax and caspase 3, which triggered apoptosis via the Bax/Bcl2 and caspase pathway. Also, TEB administration resulted in altered biochemical indicators of renal function and varying lesions in the overall histo-architecture of renal tissues. Taken together, our findings brought into light the renal toxicity induced by TEB, which was found to be significant at low doses.

Oxidative stress, genotoxicity, biochemical and histopathological modifications induced by epoxiconazole in liver and kidney of Wistar rats.

Epoxiconazole (EPX) is a triazole fungicide commonly used in agriculture and for domestic purposes around the world. The excessive application of this pesticide may result in a variety of adverse effects on non-target organisms, including humans. Since, the liver and kidneys are the target organs of this fungicide, potential hepatotoxic and nephrotoxic effects are of high relevance. Thus, our study aimed to investigate the toxic effects of EPX on the liver and kidney of Wistar rats. The exposure of rats to EPX at these concentrations (8, 24, 40, 56 mg/kg bw representing, respectively, NOEL (no observed effect level), NOEL × 3, NOEL × 5, and NOEL × 7) for 28 days significantly enhances hepatic and renal lipid peroxidation which is accompanied by an increase in the level of protein oxidation. Furthermore, the results of the present study clearly indicated that EPX administration induces an increase in the levels of DNA damage in a dose-dependent manner. In addition, the activities of liver and kidney antioxidant enzymes such as superoxide dismutase (SOD), catalase (CAT), glutathione peroxidase (GPx), and glutathione S-transferase (GST) are increased significantly in EPX-treated rats at concentrations of 8, 24, and 40 mg/kg bw. However, with the dose NOEL × 7 (56 mg/kg bw of EPX), the activities of CAT, GPx, and GST are decreased. Indeed, EPX-intoxicated rats revealed a significant reduction in acetylcholinesterase (AChE) activity in both liver and kidney compared with the control group. Also, our results demonstrated that the EPX administration leads to a disruption of the hepatic (aspartate aminotransferase (AST), alanine aminotransferase (ALT), alkaline phosphatase (ALP), and lactate dehydrogenase (LDH)) and renal (uric acid and creatinine) functions. The biochemical perturbations obtained in the present study are corroborated with the histopathological modifications. Since EPX treatment caused severe damage in the overall histo-architecture of liver and kidney tissues, these results suggest that administration of EPX induced a marked deregulation of liver and kidney functions. Graphical abstract.