Investigation of the effects of N-acetylcysteine on mancozeb-induced hepatotoxicity and nephrotoxicity in rats

Mancozeb is a widely used agricultural fungicide and long-term exposure is known to induce toxic effects in liver and kidney tissues. N-acetylcysteine (NAC), owing to its antioxidant properties, has been evaluated as a protective agent in various toxicities. In this thesis study, the potential protective effects of NAC against mancozeb-induced hepatotoxicity and nephrotoxicity in rats were investigated. A total of 32 adult male Wistar albino rats were used in the study. The animals were randomly divided into four groups: Control, Mancozeb (500 mg/kg), NAC (200 mg/kg), and Mancozeb (500 mg/kg) + NAC (200 mg/kg). Mancozeb was administered daily by oral gavage, while NAC was administered intraperitoneally twice a week for 28 days. At the end of the experimental period, the animals were sacrificed, and blood, liver, and kidney tissue samples were collected. Oxidative Stress Index (OSI) was measured to assess oxidative injury. It was determined that concomitant mancozeb administration led to a significant increase in TOS levels and a decrease in TAS levels, resulting in a marked elevation in the OSI value (p<0.05). NAC treatment produced significant improvements in these parameters (p<0.05). Serum biochemical analyses revealed marked increases in ALT, AST, GGT, urea, creatinine, and bilirubin levels in the mancozeb group. In the NAC administered groups, the values of these parameters were similar to those of the healthy control group (p>0.05). In the mancozeb-treated groups, increased expression of inflammation- and apoptosis-related genes (iNOS, COX-2, TNF-α, IL-1β, Bax, Caspase-3) and decreased expression of the anti-apoptotic Bcl-2 gene were detected. NAC administration resulted in significant improvement in these gene expression levels. Histopathological evaluations demonstrated structural deterioration, necrosis, cell loss, and inflammatory infiltration in liver and kidney tissues following mancozeb exposure, while NAC preserved tissue integrity and reduced damage. In conclusion, the findings demonstrate that NAC exerts a protective effect against mancozeb-induced hepatotoxic and nephrotoxic damage through its antioxidant, anti-inflammatory, and anti-apoptotic properties.