Effect of Cyclophosphamide and Its Combination with Metformin on the Survival Rate in Mice

Abstract

Background: Cyclophosphamide (CYP), an alkylating chemotherapeutic agent, is widely used to treat several types of cancer. Its toxic effects are well-established and include hepatotoxicity, nephrotoxicity, and bone marrow suppression. Metformin (MET) is an anti-diabetic medication that is considered a first-line therapy for type 2 diabetes mellitus. In this study, we aimed to investigate the effect of co-administration of MET on CYP-induced toxicity by recording the survival rate in mice.
 Methods: Fifty mice (body weight 30–35 gm) were divided into four groups as control and treatments and comprised of 12-13 animals of either sex. The animals in the control group received 4 doses of saline by injection. The animals in the CYP group received 4 doses of CYP (100 mg/kg) (intraperitoneal). The animals in the MET group received lower daily dose (30 mg/kg) in drinking water (3 mg/ml), starting 3 days prior to CYP injection and lasting until the final injection of CYP. The animals in the combination group (CYP and MET) received 4 doses of CYP (100 mg/kg) and a daily dose of MET in drinking water (3 mg/ml). The animals were observed daily to record the mortality and their body weights were recorded every alternate day. The data obtained from the study was statistically analyzed by one-way ANOVA, and p<0.05 was considered significant.
 Results: The data obtained from the study indicated that CYP administration increased the rate of mortality significantly (p < 0.01) when compared to the control animals, while MET reduced the rate. When the combination of CYP and MET was tested, the mortality rate was found to be increased. Both CYP and MET significantly reduced the body weight compared to the control animals.
 Conclusion: The results indicated that the combination of CYP and MET reduced the survival rate of animals, suggesting that although MET possesses anti-proliferative action, it has the potential to increase the toxic effects of CYP when combined with CYP.