DefinePK

Abstract

Background and Objective: Metformin (MET) has been shown to reduce the toxicity of chemotherapy and thereby improve patient survival rates. The present study aimed to determine the effects of MET treatment on survival of rats receiving the CMF chemotherapy protocol consisting of cyclophosphamide (CYP), methotrexate (MTX) and 5-fluorouracil (5-FU). Materials and Methods: Forty male rats were divided into 4 groups (n = 10 per group): the control group, which received a single dose of saline, the CMF group, which received a single dose of 37 mg kg–1 MTX, 75 mg kg–1 CYP and 40 mg kg–1 5-FU, the MET group, which received MET in drinking water (3 mg mL–1) every day and the CMF+MET group, which received MET in drinking water every day and a single dose of CMF (37 mg kg–1 MTX, 75 mg kg–1 CYP and 40 mg kg–1 5-FU). The survival of the animals was evaluated and their body weights were measured daily. Results: Rats that received the CMF and CMF+MET treatments showed much lower survival rates than those in the MET and control groups. The toxic effect of CMF+MET appeared to be greater than that of CMF alone, all rats in the CMF+MET treatment group died within 1 week and all rats in the CMF-treatment group died within 10 days. While rats in the control and MET groups showed an increase in body weight after initiation of treatment, those in the CMF and CMF+MET groups still living showed significant reductions in body weight. Conclusion: Administration of a single dose of CMF reduced the survival rate of rats. The addition of MET to the CMF protocol increased the toxic effect. Thus, MET increases the toxicity and body weight loss associated with CMF treatment.