Effect Of Memantine Hydrochloride On Cisplatin-Induced Toxicity With Special Reference To Renal Alterations In Mice

Background and Objective: Cisplatin is a highly nephrotoxic and widely used anti-cancer agent, used to treat various types of cancers, due to its nephrotoxicity; cisplatin use is limited, which may result from free radical damage, evidence exists that memantine reduces oxidative stress-induced damage. This study was conducted to explore the possible protective role of memantine by pre-treatment with two different therapeutic doses of orally administered memantine 5 and 10 mg kg(-1) as an agent to minimize the toxic side effects of cisplatin injected by 4 mg kg(-1) with special reference to the kidney. Materials and Methods: Seventy-five adult male BALB/c mice were divided into 5 groups: G1: No treatment, G2: Cisplatin treatment, G3: Memantine treatment, G4: Pre-treatment of 5 mg kg(-1) memantine combined with cisplatin 4 mg kg(-1), G5: Pre-treatment of 10 mg kg(-1) memantine combined with cisplatin 4 mg kg(-1). Biochemical investigations of kidney function, oxidative stress markers, histopathological examination of kidney tissues and immunohistochemical staining of myeloperoxidase (MPO) mentioned tests were performed by special kits available and following the main instructions of each test provided with kits. Results: Mice were treated only with cisplatin showed significant elevation in blood urea nitrogen (BUN), serum creatinine (Scr), alkaline phosphatase (ALP), alanine aminotransferase (ALT) and aspartate aminotransferase (AST); malondialdehyde (MDA); high score expression of myeloperoxidase (MPO), parallel to decline in levels of glutathione (GSH), glutathione transferase (GST), superoxide dismutase (SOD), Catalase (CAT) and glutathione peroxidase (GPX) contents. Moreover, histopathological examination of kidney tissue reflected marked injury; combination treatment with memantine significantly ameliorated these parameters and showed results similar to that of the control group, indicating its renoprotective effect. Conclusion: These findings showed that pre-treatment with 5 mg kg(-1) memantine offered partial protection while the 10 mg kg(-1) of memantine showed complete protection against cisplatin-induced renal cellular damage.