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Ameliorative effect of metformin on methotrexate-induced genotoxicity: An in vitro study in human cultured
Abeer M Rababa'H1, Karem H Alzoubi1, Omar F Khabour2
1Department of Clinical Pharmacy, College of Pharmacy, Jordan University of Science and Technology, Irbid 22110, Jordan.
Abstract:
Methotrexate is a folic acid antagonist that has been shown to be genotoxic to normal healthy cells. Metformin is an insulin-sensitizing agent, with multiple potential pharmacodynamic profiles. The aim of the present study was to evaluate the genotoxic effect of methotrexate on DNA and the potential ameliorative effect of metformin on chromosomal damage induced by methotrexate. The present study was performed in vitro, and the frequency of chromosomal aberrations (CAs) and sister chromatid exchanges (SCEs) in human cultured lymphocytes were measured. Blood samples from five non-smoking healthy men aged 20-35 years were donated and used in the present study. Treatment of cultured blood cells with methotrexate significantly increased the number of cells with CAs (P<0.0001) and the frequency of SCEs (P<0.0001). The chromosomal injury induced by methotrexate was significantly reduced by pretreatment of the samples with metformin (P<0.0001). Importantly, the treatment of the cells with metformin alone did not affect the frequency of SCEs compared with the control group (P>0.05). Additionally, methotrexate and metformin alone, and combined, induced significant decreases in the proliferative index compared with the control group (P<0.05). In conclusion, metformin ameliorated the genotoxicity induced by methotrexate in cultured human lymphocytes.
Insights
Metformin can reduce DNA damage caused by methotrexate, a common chemotherapy drug. This study shows metformin protects human lymphocytes from methotrexate
Area of Science:
- Pharmacology
- Genetics
- Toxicology
Background:
- Methotrexate is a folic acid antagonist known to be genotoxic.
- Metformin is an insulin-sensitizing agent with various pharmacological effects.
Purpose of the Study:
- To evaluate the genotoxic effect of methotrexate on DNA.
- To assess the potential ameliorative effect of metformin on methotrexate-induced chromosomal damage.
Main Methods:
- In vitro study using human cultured lymphocytes.
- Measurement of chromosomal aberrations (CAs) and sister chromatid exchanges (SCEs).
- Treatment groups included methotrexate, metformin, and combined treatments.
Main Results:
- Methotrexate significantly increased CAs and SCEs in lymphocytes (P<0.0001).
- Metformin pretreatment significantly reduced methotrexate-induced chromosomal injury (P<0.0001).
- Metformin alone did not affect SCEs; however, both drugs alone and combined decreased the proliferative index.
Conclusions:
- Metformin demonstrated an ameliorative effect on methotrexate-induced genotoxicity.
- Metformin may offer a protective strategy against methotrexate's DNA damage in lymphocytes.
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