CADMIUM-INDUCED NEPHROTOXICITY IN RHESUS-MONKEYS (MACACA-MULATTA) IN RELATION TO PROTEIN-CALORIE MALNUTRITION

In this study, we compared results obtained in protein calorie malnour ished (PCM) monkeys and controls given Cd2+ (5 mg Cd2+/kg body wt./day ) orally for 24 weeks. After 16 weeks of Cd2+ exposure, an indolent re nal failure develops in PCM monkeys which resulted in significant incr ease in urinary excretion of total protein, Cd2+, Zn2+ and Ca2+ as com pared to corresponding Cd2+-treated control group. In isolated proxima l tubule brush border membrane vesicles (BBMV), Cd2+, Zn2+ and Ca2+ tr ansport were significantly impaired in Cd2+-exposed PCM monkeys as com pared to Cd2+-treated controls. The mechanism of higher urinary excret ion of Cd2+, Zn2+ and Ca2+ was examined by analyzing the kinetic param eters of transport systems. The kinetic studies of Cd2+, Zn2+ and Ca2 transport systems in the BBMV preparations of Cd2+-exposed PCM monkey s exhibited a significant decrease in V-max and an appreciable increas e in K-m as compared to Cd2+-treated controls. These findings suggeste d that Cd2+ treatment of PCM monkeys caused either a decrease in the n umber of transporters in the brush border membrane or an increase in t he number of less active transporters for Cd2+, Zn2+ and Ca2+. Further more, brush border membrane-bound enzymes, viz. alkaline phosphatase a nd leucine aminopeptidase, activities were significantly impaired in C d2+-exposed PCM monkeys. Cadmium content in kidney cortex of Cd2+-expo sed PCM monkeys was 3.34-fold higher than Cd2+ exposed controls. These findings also established that Cd2+ not bound to metallothionein (MT) was significantly higher in Cd-exposed PCM monkeys, which may be an i mportant determinant in renal toxicity by interacting with sensitive s ites in the renal cells and causing renal damage in Cd-exposed PCM mon keys.