M. Valentovic et al., URINARY ENZYME EXCRETION AS A PARAMETER FOR DETECTION OF ACUTE RENAL DAMAGE MEDIATED BY N-(3,5-DICHLOROPHENYL)SUCCINIMIDE (NDPS) IN FISCHER-344 RATS, Journal of applied toxicology, 14(4), 1994, pp. 281-285
The kidney has been identified as the specific target organ for in viv
o exposure to an agricultural fungicide, N-(3,5-dichlorophenyl)succini
mide (NDPS). The goal of this study was to determine if urinary protei
n and enzyme excretion were sensitive, non-invasive markers for NDPS-i
nduced renal damage. The proximal tubular enzymes that were monitored
were the brush-border enzyme alkaline phosphatase (ALP) and the lysoso
mal enzyme N-acetyl-beta-D-glucosaminidase (NAG). Male Fischer 344 (F3
44) rats were injected intraperitoneally (i.p.) with 0.2 or 1.0 mmol k
g(1) NDPS. Control animals were injected i.p. with sesame oil (2.5 mi
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 we
re 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 co
mparable between 0.2 mmol kg(-1) NDPS-treated and control groups for a
ll other time periods. Administration of a marked nephrotoxicant dose
(1.0 mmol kg(-1)) was associated with elevated levels of urinary prote
in, NAG and ALP beginning 0-3 h after treatment when compared to the c
ontrol group or to respective baseline values. It was concluded from t
hese studies that measurement of urinary protein as well as the releas
e of ALP and NAG were sensitive markers of renal damage produced by ND
PS.