Reduction of hyperlipidemia and proteinuria without growth retardation in nephritic rats by amino acids-fortified low casein diets

Abstract

Effects of low casein diets supplemented with either cystine alone, cystine plus glycine, or cystine plus threonine on hyperlipidemia and proteinuria were studied in rats with nephrotoxic serum nephritis. Rats were maintained on experimental diets for 14 days after an injection of nephrotoxic serum. An 8.5% casein diet, as compared with a basal 20% casein diet, improved both the hyperlipidemia and proteinuria incident to nephrotoxic serum nephritis but retarded the growth of rats. The supplement of 0.3% cystine to the 8.5% casein diet alleviated the growth retardation without loss of the reductive effect on hyperlipidemia and proteinuria but caused fatty liver. Glycine (2%) failed, but threonine (0.36%) succeeded in diminishing the cystine-induced fatty liver when concomitantly added with cystine (0.3%) to the 8.5% casein diet. An 8% casein diet supplemented with cystine and threonine was also found to reduce hyperlipidemia and proteinuria without growth retardation and fatty liver induction in nephritic rats. Fecal excretion of both neutral and acidic steroids in the 8% casein diet supplemented with cystine and threonine diet-fed nephritic rats was significantly higher than that in the 20% casein diet-fed nephritic rats. Hepatic cholesterol synthesis was unchanged between the two groups, whereas fatty acid synthesis of the 8% casein supplemented with cystine and threonine diet-fed rats was higher than that of 20% casein diet-fed animals. These results suggest that cystine-threonine-supplemented low casein diets have beneficial effects on hyperlipidemia and proteinuria with neither growth retardation nor fatty liver induction in nephritis. They also suggest that the hypocholesterolemic effect of the 8% casein supplemented with cystine and threonine diet in nephritic rats may be, at least in part, attributed to an increased excretion of steroids.