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Antigenotoxic effects of ascorbic acid against megestrol acetate-induced genotoxicity in mice
Yasir Hasan Siddique1, Tanveer Beg, Mohammad Afzal
1Section of Genetics, Department of Zoology, Faculty of Life Sciences, Aligarh Muslim University, Aligarh, India. yasir_hasansiddique@rediffmail.com
Abstract:
The genotoxicity of megestrol acetate was studied in mouse bone marrow cells using sister chromatid exchanges (SCEs) and chromosomal aberrations (CAs) as parameters. Megestrol acetate (8.12, 16.25 and 32.50 mg/ kg of body weight) was injected intraperitoneally separately in different groups of animals. Both CAs and SCEs were statistically increased at 16.25 and 32.50 mg/kg of body weight. Our earlier in vitro studies show the generation of free oxygen radicals, by synthetic progestins responsible for the genotoxic damage. As the genotoxic effects of steroids can be reduced by natural products having antioxidant properties, and ascorbic acid possesses antioxidant activity, ascorbic acid (20, 40 or 60 mg/kg of body weight) administered together with megestrol acetate (32.50 mg/kg of body weight) significantly decreased CAs and SCEs, suggesting an antigenotoxic role of ascorbic acid against megestrol acetate-induced genotoxic damage in mice bone marrow cells. The antigenotoxic effect was clearly dose dependent. The highest protective effect was observed at 60 mg/kg body weight of ascorbic acid treated with 32.50 mg/kg body weight of megestrol acetate.
Insights
Megestrol acetate increased genotoxicity in mice, evidenced by chromosomal aberrations (CAs) and sister chromatid exchanges (SCEs). Ascorbic acid demonstrated antigenotoxic effects, significantly reducing this megestrol acetate-induced damage in a dose-dependent manner.
Area of Science:
- Toxicology
- Genetics
- Pharmacology
Background:
- Synthetic progestins like megestrol acetate can induce genotoxicity.
- This damage is potentially mediated by the generation of free oxygen radicals.
- Antioxidant natural products may mitigate steroid-induced genotoxic effects.
Purpose of the Study:
- To investigate the genotoxicity of megestrol acetate in mouse bone marrow cells.
- To evaluate the antigenotoxic potential of ascorbic acid against megestrol acetate-induced damage.
- To determine the dose-dependent effects of ascorbic acid.
Main Methods:
- Mice were administered varying doses of megestrol acetate intraperitoneally.
- Sister chromatid exchanges (SCEs) and chromosomal aberrations (CAs) were analyzed in bone marrow cells.
- Ascorbic acid was co-administered with megestrol acetate to assess protective effects.
Main Results:
- Megestrol acetate significantly increased SCEs and CAs at doses of 16.25 and 32.50 mg/kg.
- Co-administration of ascorbic acid dose-dependently decreased megestrol acetate-induced CAs and SCEs.
- A significant protective effect was observed with 60 mg/kg ascorbic acid.
Conclusions:
- Megestrol acetate exhibits genotoxic potential in mouse bone marrow.
- Ascorbic acid acts as an antigenotoxic agent against megestrol acetate-induced genotoxicity.
- Ascorbic acid's protective effect is dose-dependent, highlighting its therapeutic potential.
