Oxidative Stress and Structural Damage Underlie Hepatic, Renal, and Intestinal Toxicity of Dodine in Rats Following Subacute Exposure

Pesticide use poses a significant threat to environmental integrity and animal health. Dodine (n-dodecylguanidine acetate), a widely used fungicide in horticulture, lacks comprehensive toxicological evaluation in animal systems, particularly with respect to systemic toxicity. This study investigated the multifaceted toxicity of dodine in Wistar rats, focusing on oxidative stress, biochemical alterations, tissue damage, and structural changes in liver, kidney, and intestinal tissues. Rats were divided into four groups (n = 6 per group) and administered dodine orally at 0 (control), 5, 20, and 80 mg/kg body weight daily for 30 days. Results revealed a significant increase in malondialdehyde (MDA) levels (p < 0.001) in all treated groups, indicating elevated lipid peroxidation. Concurrently, antioxidant enzymes such as superoxide dismutase (SOD), catalase (CAT), and glutathione peroxidase (GPx) showed a dose-dependent reduction, particularly in the 20 and 80 mg/kg groups. Histopathological analysis revealed moderate to severe tissue degeneration, inflammation, and necrosis in hepatic, renal, and intestinal sections of medium- and high-dose groups. FTIR spectroscopy revealed molecular changes in protein and lipid functional groups, while scanning electron microscopy (SEM) showed significant ultrastructural damage in tissue morphology. Additionally, serum biomarkers including alanine aminotransferase, aspartate aminotransferase, alkaline phosphatase, creatinine, and urea levels were significantly elevated (p < 0.001), supporting evidence of hepatic and renal dysfunction. In conclusion, dodine induces dose-dependent oxidative damage and systemic toxicity in Wistar rats. These findings underscore the need for re-evaluating its safety and encourage further investigation, particularly at subchronic and environmentally relevant exposure levels, highlighting the need for stricter regulatory evaluation and further toxicological studies at environmentally relevant doses.