Isometamidium chloride alters redox status, down-regulates and genes while modulating at proteomic level in .

As trypanocide, several side effects have been reported in the use of Isometamidium chloride. This study was therefore, designed to evaluate its ability to induce oxidative stress and DNA damage using as a model organism. The LC of the drug was determined by exposing the flies (1-3 days old of both genders) to six different concentrations (1 mg, 10 mg, 20 mg, 40 mg, 50 mg and 100 mg per 10 g of diet) of the drug for a period of seven days. The effect of the drug on survival (28 days), climbing behavior, redox status, oxidative DNA lesion, expression of and (Poly-ADP-Ribose Polymerase-1) genes after five days exposure of flies to 4.49 mg, 8.97 mg, 17.94 mg and 35.88 mg per 10 g diet was evaluated. The interaction of the drug with p53 and PARP1 proteins was also evaluated. The result showed the LC of isometamidium chloride to be 35.88 mg per 10 g diet for seven days. Twenty-eight (28) days of exposure to isometamidium chloride showed a decreased percentage survival in a time and concentration-dependent manner. Isometamidium chloride significantly ( < 0.05) reduced climbing ability, total thiol level, Glutathione-S-transferase, and Catalase activity. The level of HO was significantly ( < 0.05) increased. The result also showed significant ( < 0.05) reduction in the relative mRNA levels of and genes. The molecular docking of isometamidium with p53 and PARP1 proteins showed high binding energy of -9.4 Kcal/mol and -9.2 Kcal/mol respectively. The results suggest that isometamidium chloride could be cytotoxic and a potential inhibitor of p53 and PARP1 proteins.