Protective effects of a novel pyrazolecarboxamide derivative against lead nitrate induced oxidative stress and DNA damage in Clarias gariepinus

Abstract Pyrazole derivatives display diverse biological and pharmacological activities. The aim of this study is to investigate the antioxidant properties of a novel pyrazolecarboxamide derivative (4-amino-N-[(4-chlorophenyl)]-3-methyl-1-phenyl-1H-thieno [2, 3-c] pyrazole-5-carboxamide) in African catfish, Clarias gariepinus , exposed to 1 mg/L PbNO 3 . Fish were intramuscularly injected with pyrazole-5-carboxamidederivative according to the following groupings: Group 1 (control), Group 2 (1 mg/L lead nitrate), Group 3 (1 mg/L lead nitrate + 5 mg pyrazole derivative/kg body weight), and Group 4 (1 mg/L lead nitrate + 10 mg pyrazole derivative/kg body weight) for two weeks and four weeks. Lead nitrate (1 mg/L) caused significant elevation of serum aspartate aminotransferase (AST), alanine aminotransferase (ALT), creatinine, uric acid, cholesterol, and glucose-6-phosphate dehydrogenase (G6PDH) compared to the control group after two and four weeks of exposure, while serum total lipids, alkaline phosphatase (ALP), and lactate dehydrogenase (LDH) were significantly reduced compared to the control group. Furthermore, levels of antioxidant enzymes superoxide dismutase (SOD) and catalase (CAT) and total antioxidant capacity (TAC) were reduced in group 2 compared to the control group. However, in group 2, hepatic lipid peroxidation (LPO) and DNA fragmentation percentage were significantly increased compared to the control group. Histopathological changes in the liver of lead-exposed groups included marked disturbance of hepatic tissue organization, degeneration of hepatocytes, dilation of blood sinusoids and the central vein as well as necrosis. Injection of pyrazole derivative for two weeks and four weeks reversed alterations in biochemical parameters, antioxidant biomarkers, lipid peroxidation, hepatic DNA damage, and histopathological changes in liver tissue induced by 1 mg/L lead nitrate. This amelioration was higher in response to high-dose pyrazole derivative (10 mg) at the fourth week of exposure, showing concentration-and time-dependency. Overall, the sensitized derivative pyrazolecarboxamide is likely a useful tool to minimize the effects of lead toxicity due to its potent antioxidant activity.