The Potential Preventive Role of Dapagliflozin and Metformin Alone or in Combination on the Cisplatin-Induced Renal Damage in Adult Male Albino Rats

Abstract

Background: Chronic kidney disease is currently a worldwide health problem with rising incidence and poor outcomes. Cisplatin (CP) is an important platinum-based anticancer drug. However, nephrotoxicity is the main limiting adverse effect. Aim: The objective of this work was to compare the probable protective effect of dapagliflozin and metformin alone or in combination on CP-induced renal damage in adult male albino rats using a histological study. Material and Methods: A total of 60 adult male albino rats were used in this study. Rats were divided into five main groups: group I (control group), which included 15 rats that were divided into four subgroups: Subgroup Ia (negative control group), which included 5 rats that received no treatment for the same periods as the experimental animals. Subgroup Ib, which included 5 rats that received intraperitonial saline once a week for 4 weeks. Subgroup Ic (dapagliflozin group), which included 5 rats that received dapagliflozin (1 mg/kg/day) by nasogastric tube for 4 weeks. Subgroup Id (metformin group), which included 5 rats that received metformin (250 mg/kg/day) by nasogastric tube for 4 weeks. The experimental group included 40 rats and was divided into the following groups: Group II (CP group), which included 10 rats that received CP (9 mg/kg) intraperitoneally once a week for 4 weeks. Group III (CP + dapagliflozin treated group), which included 10 rats that received CP (9 mg/kg) intraperitoneally once a week + dapagliflozin (1 mg/kg/day) by gavage for 4 weeks. Group IV (CP + metformin-treated group), which included 10 rats that received CP (9 mg/kg) intraperitoneally once a week + metformin (250 mg/kg/day) by gavage for 4 weeks. Group V (CP + dapagliflozin + metformin-treated group), which included 10 rats that received CP, dapagliflozin, and metformin as the previous doses for 4 weeks. Kidney specimens were subjected to histological (light and electron microscopic examination). The data were analyzed statistically. Results: The current study of group II showed disturbed normal histological architecture of renal cortex structure but groups III and IV resulted in mild preservation of the normal histological architecture of the renal cortex. Group V showed complete preservation of normal histological architecture of the renal cortex. Conclusion: CP induced structural changes on the renal cortex of adult male albino rats. Most of these changes were prevented by the usage of dapagliflozin or metformin. While the combination of both drugs protected the renal cortex.