The Effect of Atorvastatin on the Development of Puromycin Aminonucleoside(PAN)-induced Nephrosis in Rats

ABSTRACT

PURPOSE: Several studies have suggested that hyperlipidemia might be a causative factor contributing to the progression of initial glomerular injury through the development of glomerulosclerosis. We examined the potential beneficial effect of atorvastatin - which blocks the rate limiting step of cholesterol synthesis by inhibiting HMG-CoA reductase - in PAN- induced nephrosis. MATERIALS AND METHODS: Glomerulosclerosis was induced in Sprague-Dawley male rats by repeated administration of PAN. Sprague-Dawley male rats were divided into 3 groupsgroup I(control), group II(PAN 20 mg/kg, subcutaneous injection), group III(PAN 20 mg/kg subcutaneous injection and atorvastatin 50 mg/kg/day per oral). On the 11th week, upon sacrifice of the experimental animals, blood sampling, 24-hr urine collection and nephrectomy were performed. RESULTS: Group III had significantly lower BUN and higher serum albumin(30.9+/-17.2 vs. 17.3+/-2.5 mg/dL; 2.3+/-0.1 vs. 2.5+/-0.2 g/dL, P0.05) compared with group II. Atorvastatin administration lowered the glomerular sclerosing index significantly(26.2% vs. 13.3%, P<0.05). CONCLUSION: Puromycin-induced glomerulosclerosis could be ameliorated by the reduction of hyperlipidemia with atorvastatin. This suggests that hyperlipidemia contributes to the pathogenesis of glomerulosclerosis.