Failure of antioxidant therapy to attenuate interstitial disease in rats with reversible nephrotic syndrome.

Journal of the American Society of Nephrology : JASN
A Drukker, A A Eddy

Abstract

The present two studies were designed to determine whether oxidized LDL contributes to the tubulointerstitial changes seen in rats during the acute phase of acute puromycin aminonucleoside nephrosis (PAN). In the single-dose study, rats were given one injection of puromycin aminonucleoside (PA; 15 mg/100 g body wt) and killed 1, 2, or 3 wk thereafter. The four animal groups were saline controls, PAN controls, PAN plus probucol, and PAN plus lovastatin. This study showed that the addition of probucol significantly reduced the mean levels of serum cholesterol and renal lipid-peroxidation products, an effect not seen with lovastatin therapy. Compared with saline controls, PAN controls had a significant increase in total kidney collagen (7.9 +/- 1.2 versus 5.9 +/- 0.6 mg/kidney at 3 wk). Neither probucol nor lovastatin therapy attenuated the interstitial inflammation or fibrosis. In the multidose study, rats were given the same initial PA dose and were uninephrectomized on day 12. They were killed on day 35 after two smaller PA doses were given on days 16 and 23. Animal groups were saline controls, PAN controls, PAN plus probucol, and PAN plus vitamin E. Hepatic lipid-peroxidation products were significantly lower in the probucol-t...Continue Reading

Citations

Sep 7, 1999·Journal of the American Society of Nephrology : JASN·A BesarabJ Yee
Mar 3, 2005·European Journal of Pharmacology·Takeyuki YatsuAkihiro Tanaka

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