Impact of Metformin on Hypothyroidism Induced by Cyclophosphamide in Rats

Ahmad Alhowail and Maha Aldubayan

Background and Objective: Cyclophosphamide (CYP), a commonly used chemotherapeutic agent, is administered to patients to treat various cancer types. The toxic effects of this substance are widely known and can cause damage to the liver, kidneys, nervous system and bone marrow. Metformin (MET) is frequently prescribed medication for diabetes mellitus type-2, known for its effectiveness in managing blood sugar levels. Present research aims to study the effect of co-administering MET on CYP-induced hypothyroidism by determining the level of thyroid hormones. Materials and Methods: Forty rats, with a body weight ranging from 220 to 250 g, were divided into four groups of ten animals, each for control and treatment purposes. Saline was given to animals in control group. The CYP-treated group was administered four doses of CYP (100 mg/kg each) by intraperitoneal route. The MET administered animals received 3 mg/mL dose mixed in their drinking water, starting one day preceding to the CYP jab and continued until the last dose. Further, the combination group of animals was administered four doses of a CYP and a daily MET through their drinking water. Daily observations were made on the animals for any signs of mortality, while blood samples were collected to measure TSH as well as thyroid hormones (free and total T3 and T4 concentrations). Results: The study’s data suggested that the administration of CYP resulted in a higher mortality rate than the control animals. Additionally, when combined with MET, CYP further decreased the survival rate. Furthermore, a significant reduction in the concentrations of free and total T3 and T4 were observed in animals treated with CYP and CYP+MET upon comparison with control group. On the other hand, no significant changes in TSH level were recorded across all groups. Conclusion: The findings of the study revealed that the induction of hypothyroidism by CYP was not reduced by co-treatment with MET. This suggests that while MET does have anti-proliferative properties but the toxic effects of CYP was augmented, when used together.

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