ASSESSMENT OF IMIDAZOLE DERIVATIVE {1-(1,4,5-TRIPHENYL- 1H-IMIDAZOLE-2-YL) NAPHTHALEN-2-OL} FOR OXIDATIVERELATED TOXICITY IN DROSOPHILA MELANOGASTER

OLUWAYEMI, ELIZABETH (2021) ASSESSMENT OF IMIDAZOLE DERIVATIVE {1-(1,4,5-TRIPHENYL- 1H-IMIDAZOLE-2-YL) NAPHTHALEN-2-OL} FOR OXIDATIVERELATED TOXICITY IN DROSOPHILA MELANOGASTER. Masters thesis, Landmark University, Omu Aran, Kwara State.

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Abstract

T Imidazole-based compounds possess several pharmacological properties and play crucial roles in diverse biochemical processes. In addition, recent studies have shown that a new series of imidazole derivatives could be lead candidates for early drug development for parasitic diseases. Hence, this study seeks to investigate the toxicity of a new imidazole-based compound 1-(1,4,5-triphenyl-1H-imidazol-2-yl) naphthalen-2-ol through the evaluation of selected oxidative stress and antioxidant markers. In this study, both male and female D. melanogaster (3-5 days old) were fed a diet containing the imidazole derivative (20, 50, and 100 mg IMZ/kg diet) for 5 days. After cessation of imidazole treatment, half the population of the imidazole-exposed flies were further allowed to have a normal diet for an additional 5 days to see if the toxic effect would be resolved. The survival rate of flies was determined. In addition, levels of kynurenine, glutathione S‐ transferase, glutathione peroxidase, catalase activity, nitric oxide level, total protein level, lipid peroxidation, DNA fragmentation, and protein carbonyl were evaluated. The imidazole derivative did not significantly affect the survival rate of flies. The survival rate of flies decreased by 5.3, 8.1 and 7.4% respectively for 20, 50 and 100 mg IMZ/kg diet relative to 2.4% in the control group. Furthermore, when compared to the control group, there was a significant (p<0.05) increase in reduced glutathione (GSH) levels. Also, the activity of catalase was significantly increased in flies fed with 50 mg IMZ/diet. In contrast, non-significant (p>0.05) increases were observed in the levels of glutathione peroxidase, glutathione transferase, total protein, nitric oxide, and lipid peroxidation for flies treated with an IMZsupplemented diet when compared to the control. Furthermore, a significant increase was observed in the levels of protein carbonyl and DNA fragmentation of flies fed with (100 mg of IMZ/kg diet) The findings suggest that administration of IMZ at the highest concentration (100 mg IMZ/kg diet) might have caused a mild level of oxidative-related toxicity in the flies, but this was resolved following cessation of treatment. Additional research into the safety and/or toxicity of the imidazole derivative in other animal models is recommended to advance the test compound's therapeutic prospects as an alternative anti-parasite agent. Keywords: Antiparasitic; Imidazole-based compounds; Oxidative stress; Toxicity assessment.

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