Simvastatin ameliorates glomerulosclerosis in Adriamycin-induced-nephropathy rats.
The aim of this study was to investigate the effects of simvastatin, a competitive inhibitor of 3-hydroxy-3-methylglutaryl-coenzyme A (HMG-CoA) reductase, on inflammation and glomerulosclerosis in Adriamycin (ADR)-induced nephropathy. Male Sprague-Dawley rats were randomly divided into control, ADR nephrosis, and simvastatin-treated ADR nephrosis groups. ADR nephropathy was induced by a single-tail intravenous injection of ADR (6.5 mg/kg). Anti-inflammatory effects of simvastatin were studied by evaluating the expression of the inflammatory mediators interleukin-1 beta (IL-1beta), transforming growth factor-beta1 (TGF-beta1), and transcription factor nuclear factor kappa B (NF-kappaB). In addition, renal function, serum lipid levels, and histopathology were compared between groups. Simvastatin significantly decreases IL-1beta and TGF-beta1 expression and NF-kappaB activation, accompanied by significant attenuation of glomerulosclerosis and renal function at 12 weeks after ADR injection, and these changes occurred in the absence of lowering of serum lipids. These results suggest that overexpression of inflammation in the renal region may contribute to development of glomerulosclerosis in ADR-induced-nephropathy rats, and simvastatin treatment prevented glomerulosclerosis independent of the lipid-lowering effects. The beneficial effect of simvastatin might be mediated by the effect of anti-inflammatory action through a reduction of NF-kappaB activation, and IL-1beta and TGF-beta expression.
Zhang
Wei
W
Department of Nephroimmunology, Children's Hospital of Chongqing Medical University, Chongqing, People's Republic of China.
Li
Qiu
Q
Wang
Lijia
L
Yang
Xiqiang
X
D000818:Animals; D000903:Antibiotics, Antineoplastic / Q000009:adverse effects*; D004195:Disease Models, Animal; D004317:Doxorubicin / Q000009:adverse effects*; D019161:Hydroxymethylglutaryl-CoA Reductase Inhibitors / Q000494:pharmacology / Q000627:therapeutic use*; D053583:Interleukin-1beta / Q000378:metabolism; D007668:Kidney / Q000187:drug effects / Q000378:metabolism / Q000473:pathology*; D007674:Kidney Diseases / Q000139:chemically induced* / Q000473:pathology / Q000517:prevention & control*; D008297:Male; D016328:NF-kappa B / Q000378:metabolism; D051381:Rats; D017207:Rats, Sprague-Dawley; D012598:Sclerosis; D019821:Simvastatin / Q000494:pharmacology / Q000627:therapeutic use*; D053773:Transforming Growth Factor beta1 / Q000378:metabolism
D000903:Antibiotics, Antineoplastic; D019161:Hydroxymethylglutaryl-CoA Reductase Inhibitors; D053583:Interleukin-1beta; D016328:NF-kappa B; D053773:Transforming Growth Factor beta1; D004317:Doxorubicin; D019821:Simvastatin
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