Ameliorative effects of metformin on renal histologic and biochemical alterations of gentamicin-induced renal toxicity in Wistar rats

Abstract

Background: The aim of this study was to test the potential properties of metformin (MF) to protect the kidney from gentamicin (GM)-induced renal toxicity.

Materials and methods: In this preclinical study, 50 male Wistar rats were randomly divided into five groups of 10 rats in each. In the first group (group I), they were kept in the same condition as others without receiving drugs for 10 days. In group II, the rats were injected intraperitoneally with 100 mg/kg/day of GM for 10 consecutive days. Group III rats received 100 mg/kg/day MF orally for 10 days. In group IV, the rats received GM (100 mg/kg; intraperitoneally) for 10 days and 100 mg/kg/day MF orally for the next 10 days. In the last group (group V), the rats received a combination of GM 100 mg/kg/day intraperitoneally and MF 100 mg/kg/day orally for 10 days simultaneously. Serum blood urea nitrogen (BUN) and creatinine (Cr) values were measured and renal tissues of the animals were processed for light microscope examination.

Results: The levels of BUN in groups II, IV, and V, and also the serum level of Cr in groups II and V were increased significantly after the experiment. Furthermore, post-treatment with MF or co-treatment with MF could prevent the elevation of serum BUN and Cr induced by GM and also attenuates the damage score (P < 0.05).

Conclusions: MF may prevent or ameliorate GM-induced acute renal failure, and therefore it might be beneficial in patients under treatment with this medicine.

Keywords: Gentamicin; metformin; nephroprotection; tubular toxicity.

Figure 1

The serum levels of BUN and Cr before and after the experiment in five groups of animals. Group I, sham group; group II, positive control group treated with gentamicin; group III, treated with metformin; group IV, treated with gentamicin for 10 days and post-treatment with metformin for the next 10 days; and group V, co-administration of metformin and gentamicin for 10 days. The symbols (*) and (†) stand for significant difference before the experiment (P < 0.05) and significant difference from positive control group (P < 0.05), respectively

Figure 2

The pathology damage score in five groups of animals. Group I, sham group; group II, positive control group treated with gentamicin; group III, treated with metformin; group IV, treated with gentamicin for 10 days and post-treatment with metformin for the next 10 days; and group V, co-administration of metformin; and gentamicin for 10 days. The symbols (#) and (‡) stand for significant difference from group I (P < 0.05) and group II (P < 0.05), respectively