Inhibition of progression of chronic puromycin aminonucleoside nephrosis by probucol, an antioxidant.

Abstract

Oxidants have been shown to be involved in the initiation of chronic puromycin aminonucleoside nephrosis in rats, but it is uncertain whether they have a role in the progression of this disease. Rats given a single internal jugular venous bolus of puromycin aminonucleoside (PA) develop early nephrotic syndrome that subsides after about 28 days followed by a 4-wk period of minimal proteinuria and then the development of focal glomerulosclerosis and increasing proteinuria. Fifty-two rats on a high-cholesterol diet were divided into four groups. Two groups of 16 animals each received a single internal jugular venous bolus of PA. One of these groups was started on the dietary antioxidant, probucol (1% wt/wt), 4 days after the PA injection and continued on it until termination. The remaining rats were given an internal jugular venous injection of an equivolume of normal saline. Five of these animals were also started on dietary probucol 4 days after the saline injection. At 11 days postinjection all animals given PA, whether on probucol or not, developed marked proteinuria with histologically minimal glomerular change and significant increases in intraglomerular monocyte and proliferating cell nuclear antigen counts. Forty-two days after PA injection all PA-injected rats had minimal urinary protein injection and no glomerular changes. At 98 days postinjection rats given PA without probucol developed focal glomerulosclerosis and significant proteinuria compared with PA-injected rats on probucol and those injected with saline (P < 0.05). The probucol-fed PA-injected rats showed no glomerular disease and their urinary protein excretion rates were very similar to those of the saline controls. The results indicate that probucol inhibits the progression of chronic puromycin aminonucleoside nephrosis and are consistent with the suggestion that oxidants are involved in the progression of this entity.