Proquinazid, a new-generation fungicide, induces DNA damage and apoptosis via oxidative stress process in liver and kidney tissues of adult Wistar rats

Abstract

Proquinazid (PROQ) is a new fungicide used against powdery mildew infections, but little is known about PROQ toxicity. The aim of this study was to investigate the effects of PROQ in liver and kidney. Male Wistar rats were daily exposed for 28 days to 1, 2, 4, and 8 mg PROQ / kg body weight, corresponding to No-Observable Adverse Effect Level (NOAEL)/ 2, NOAEL, NOAEL × 2, and NOAEL × 4, respectively. PROQ caused histopathological disruptions in both hepatic and renal functions associated with increased plasmatic activities of alkaline phosphatase (ALP), lactate dehydrogenase (LDH), and transaminases (AST and ALT), and levels of creatinine, uric acid, and urea. Oxidative stress analysis showed that PROQ induced an increase in malondialdehyde (MDA) and protein carbonyl levels with a conspicuous disruption of superoxide dismutase, catalase, glutathione S-transferase and glutathione peroxidase activities. Oxidative stress generation was accompanied with DNA damage assessed by comet and TUNEL assays. PROQ down-regulated Bcl-2 and PCNA expression and up-regulated p53, Bax and caspase-3 expression evaluated by immunohistochemistry and western blotting. Overall, our outcomes highlighted that PROQ is a hepatotoxic and nephrotoxic fungicide that exerts its toxic effects through disruption of oxidative balance which causes genotoxic damage leading to apoptotic cell death.