Urinary enzyme excretion as a parameter for detection of acute renal damage mediated by N-(3,5-dichlorophenyl)succinimide (NDPS) in Fischer 344 rats.

Abstract

The kidney has been identified as the specific target organ for in vivo exposure to an agricultural fungicide, N-(3,5-dichlorophenyl)succinimide (NDPS). The goal of this study was to determine if urinary protein and enzyme excretion were sensitive, non-invasive markers for NDPS-induced renal damage. The proximal tubular enzymes that were monitored were the brush-border enzyme alkaline phosphatase (ALP) and the lysosomal enzyme N-acetyl-beta-D-glucosaminidase (NAG). Male Fischer 344 (F344) rats were injected intraperitoneally (i.p.) with 0.2 or 1.0 mmol kg-1 NDPS. Control animals were injected i.p. with sesame oil (2.5 ml kg-1). Urine was collected on ice 0-3, 3-6 and 6-24 h after NDPS or vehicle injection. Urinary protein and urinary NAG excretion levels were elevated (P < 0.05) above the control levels 0-3 h after treatment with 0.2 mmol kg-1 NDPS. Urinary protein and enzyme excretion was comparable between 0.2 mmol kg-1 NDPS-treated and control groups for all other time periods. Administration of a marked nephrotoxicant dose (1.0 mmol kg-1) was associated with elevated levels of urinary protein, NAG and ALP beginning 0-3 h after treatment when compared to the control group or to respective baseline values. It was concluded from these studies that measurement of urinary protein as well as the release of ALP and NAG were sensitive markers of renal damage produced by NDPS.