Amniotic Fluid-Derived Mesenchymal Stem Cells Cut Short the Acuteness of Cisplatin-Induced Nephrotoxicity in Sprague-Dawley Rats

BACKGROUND AND OBJECTIVES: Cisplatin is a nephrotoxic chemotherapeutic agent. So, preventive measures worth to be evaluated. Human amniotic fluid stem cells (hAFSCs) in prevention or amelioration of cisplatin-induced acute kidney injury (AKI) in Sprague-Dawley rates have been tested. METHODS: 80 Sprague-Dawley rats (250~300 g) were used and divided into 4 major groups, 20 rats each. Group I: Saline-injected group. Group II: Cisplatin-injected group (5 mg/kg I.P). Group III: Cisplatin-injected and hAFSCs-treated group (5×106 hAFSCs I.V. one day after cisplatin administration). Group IV: Cisplatin-injected and culture media-treated group. Each major group was further divided into 4 equal subgroups according to the timing of sacrifice; 4, 7, 11 and 30 days post-cisplatin injection. Renal function tests were done. Kidney tissue homogenate oxidative stress parameters malondialdehyde (MDA), superoxide dismutase (SOD) and glutathione (GSH) were determined. Histopathological scoring systems for active injury, regenerative and chronic changes were analyzed separately. RESULTS: hAFSCs characterization and differentiation was proved. Cisplatin injection resulted in a significant increase in serum creatinine and MDA and decrease in SOD, GSH and creatinine clearance. These changes were attenuated early by day 4 with the use of hAFSCs. Cisplatin injection induced tubular necrosis, atrophy, inflammatory cells infiltration and fibrosis. The use of hAFSCs was associated with significantly lowered injury score at day 4, 7, 11 and 30 with marked regenerative changes starting from day 4. CONCLUSION: hAFSCs have both a protective and regenerative activities largely through an antioxidant activity. This activity cut short the acuteness of cisplatin nephrotoxicity.

potential renoprotective effect of selective cyclooxygenase inhibitors in experimental diabetic nephropathy

Diabetic nephropathy is a major microvascular complication of diabetes and eventually leads to end-stage renal disease. The present study designed to evaluate the renal effects of selective COX-2 inhibitors on the progression of renal injury in experimental model of diabetic nephropathy. Fifty rats were randomly divided into five equal groups: normal control rats, streptozotocin [STZ]-induced diabetic rats without treatment, STZ-induced diabetic rats treated with celecoxib, STZ-induced diabetic rats treated with enalapril, and STZ-induced diabetic rats treated with combination. Sixteen weeks later, serum glucose, renal functions, and oxidative stress parameters were evaluated. Periodic acid-Schiff [PAS] staining was used to examine the morphological changes by light microscopy. STZ-induced diabetes led to development of diabetic nephropathy associated with increased oxidative stress. Both celecoxib and enalapril produced comparable level of renoprotection manifested by significant decrease of serum creatinine and microalbuminuria, which was accompanied by significant decrease of renal malondialdyehyde content, significant increase of renal reduced glutathione content and superoxide dismutase activity. Glomerulosclerosis seen in untreated-diabetic group were prevented by both celecoxib and enalapril. Combination treatment was superior in renoprotective effects. In conclusion, the selective COX-2 inhibitor celecoxib may prevent or retard the development of diabetic nephropathy