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