Linagliptin Renoprotective Role in Rats with Cisplatin-induced Nephrotoxicity

Background: Nephrotoxicity is a common type of toxicity associated with the use of many chemotherapeutic agents, especially cisplatin. The prevalence of cisplatin nephrotoxicity is about 28% to 36% after a single dose. Cisplatin is an important agent for treating a wide range of solid tumors, so nephroprotection is very important. Linagliptin is an antidiabetic drug that acts by inhibiting the enzyme dipeptidyl peptidase-4. This group of drugs has pleiotropic effects that may reduce nephrotoxicity caused by cisplatin. Objectives: To evaluate the nephroprotective effect of linagliptin against cisplatin-induced nephrotoxicity. Materials and Methods: A total of 28 male rats were divided into four groups: control, cisplatin alone, cisplatin with linagliptin, and linagliptin alone. The rats were administered cisplatin (7 mg/kg, IP single dose on day 8) alone or in combination with linagliptin (3 mg/kg/day, orally for 14 days) and the control group received only distal water. After 2 weeks, blood samples were collected for measurement of tumor necrotic factor- α , caspase-3, total antioxidant capacity, urea, and creatinine. Animals were then sacrificed and the kidney was removed for histopathological studies. Data are expressed as the mean ± standard error of the mean. Results: Linagliptin treatment significantly minimized cisplatin-induced nephrotoxicity and improved kidney function by reducing serum urea, creatinine, caspase-3, and TNF- α levels and increasing serum total antioxidant capacity level. In addition, linagliptin improved histopathological changes induced by cisplatin administration. Conclusion: Linagliptin may serve as a nephron-protectant when administered concomitantly with cisplatin.