EFFECT OF MAST CELL STABILIZER, KETOTIFEN ON STREPTOZOTOCIN INDUCED EXPERIMENTAL DIABETIC NEPHROPATHY IN RATS

Background: Infiltration and degranulation of mast cells has been noted to occur in renal diseases and are reported to play a key role in inflammation. Degranulation of mast cells releases various inflammatory mediators such as cytokines, endothelins, growth factors and proteolytic enzymes. Ketotifen has been reported as stabilizer of mast cells. Thus, the present study is designed to investigate the involvement of mast cells in diabetes induced nephropathy. Materials and methods: Male Wistar rats weighing 200-250 gm were given streptozotocin (50 mg/kg., i.p once) to induce diabetes mellitus and maintained hyperglycemic for eight weeks to produce nephropathy. Diabetes was assessed by serum glucose level and nephropathy was assessed by estimating serum creatinine level, blood urea nitrogen (BUN), total urinary proteins, oxidative stress (lipid peroxidation, reduced glutathione), renal collagen content and integrity of kidney was assessed histopathologically by Hematoxylin Eosin staining and for mast cells toluidine blue staining was done. After one week of streptozotocin, diabetic rats were treated with ketotifen (1 mg/kg., p.o) for 7 weeks. Standard mast cell degranulator compound 48/80 (1.5 mg/kg, 3 days i.p) in diabetic rats was also employed. Lisinopril is employed as a standard drug for nephropathy. Results: Administration of Ketotifen (1 mg/kg., p.o) for 7 weeks significantly improved parameters employed of renal function and nephropathy in comparison to Diabetic group. In same model lisinopril employed as standard drug also significantly improved parameters. However in diabetic group compound 48/80 significantly increased the damage in terms of parameters used. Conclusion: Thus it may be concluded that ketotifen exerts ameliorative effect in diabetic nephropathy possibly by inhibiting degranulation of mast cells and reducing oxidative stress.