ASSESSMENT OF REDOX STATUS AND THE EXPRESSION OF P53 AND PARP1 GENES IN DROSOPHILA MELANOGASTER EXPOSED TO ISOMETAMIDIUM CHLORIDE

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Date
2023-06
Authors
APOLLOS, SHADRACK DANGABAR
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Isometamidium chloride is a drug used in the prevention and treatment of Animal African Trypanosomiasis (AAT). However, several side effects have been reported in the use of this drug. This study was, therefore, designed to evaluate its ability to induce oxidative stress and DNA damage using D. melanogaster as a model organism. The LC50 of the drug was determined by exposing the flies (1-3 days old of both genders) to six different concentrations (0.1 mg, 1 mg, 2 mg, 4 mg, 5 mg and 10 mg per gram 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 p53 and PARP1 (Poly-ADP-Ribose Polimerase-1) genes after five days exposure of flies to 0.449 mg, 0.897mg, 1.794mg and 3.588 mg/g of diet was evaluated. The interaction of the drug in silico with p53 and PARP1 proteins was also evaluated. The result showed the LC50 of isometamidium chloride to be 3.588 mg/g diet for seven days. Twenty eight (28) days exposure to isometamidium chloride showed a decreased percentage survival in a time and concentration-dependent manner. Isometamidium chloride significantly (p<0.05) reduced climbing ability, total thiol level, glutathione-S-transferase and catalase activity. The level of H2O2 was significantly (p<0.05) increased. The result also showed significant (p<0.05) reduction in the relative mRNA levels of p53 and PARP1 genes. The in silico molecular docking of isometamidium chloride with p53 and PARP1 proteins of D. melanogaster and Bos taurus showed high binding affinity of -9.4Kcal/mol, -9.2Kcal/mol and -8.1Kcal/mol and - 10.3Kcal/mol respectively. The results suggest that isometamidium chloride could be cytotoxic and a potential modulator of p53 and PARP1 proteins.
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A THESIS SUBMITTED TO THE SCHOOL OF POSTGRADUATE STUDIES, AHMADU BELLO UNIVERSITY ZARIA IN PARTIAL FULFILLMENT OF THE REQUIREMENTS FOR THE AWARD OF MASTER DEGREE IN BIOTECHNOLOGY DEPARTMENT OF BIOCHEMISTRY, FACULTY OF LIFE SCIENCES, AHMADU BELLO UNIVERSITY, ZARIA, NIGERIA
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