N‐Acetylcysteine Attenuates Mancozeb‐Induced Hepatorenal Injury by Modulating Oxidative Stress, Inflammatory Signaling, and Apoptotic Pathways in Rats

Mancozeb (MNZ), a widely used dithiocarbamate fungicide, has been associated with oxidative stress-mediated organ toxicity in nontarget species. The present study investigated the potential protective effects of N-acetylcysteine (NAC) against MNZ-induced hepatotoxicity and nephrotoxicity in rats. Thirty-two adult male Wistar rats were randomly assigned to four groups: Control, NAC (200 mg/kg, i.p.), MNZ (500 mg/kg, p.o.), and MNZ + NAC for 28 days. Serum biochemical parameters, tissue oxidative status, inflammatory cytokine levels, apoptosis-related gene expression, and histopathological alterations were evaluated in liver and kidney tissues. MNZ administration significantly elevated serum ALT, AST, GGT, bilirubin, creatinine, and urea levels compared with controls (p < 0.05). In both liver and kidney tissues, MNZ caused a significant increase in the oxidative stress index (OSI) by elevating total oxidant status (TOS) and reducing total antioxidant status (TAS) (p < 0.001). Pro-inflammatory cytokines (IL-1β, IL-6) and the mRNA expression of TNF-α, iNOS, COX-2, Bax, and caspase-3 were significantly upregulated, whereas Bcl-2 expression and the Bcl-2/Bax ratio were reduced. Histopathological evaluation confirmed substantial structural deterioration in both organs. NAC co-administration significantly attenuated biochemical abnormalities, restored redox balance, modulated inflammatory and apoptotic gene expression, and markedly improved tissue architecture. These findings indicate that MNZ induces hepatorenal injury through oxidative stress-associated inflammatory and apoptotic processes, and that NAC confers significant protective effects by restoring cellular redox homeostasis and limiting downstream tissue damage.