Acute nephrotoxicity induced by N-(3,5-dichlorophenyl)-3-hydroxysuccinamic acid in Fischer 344 rats.

Abstract:

:N-(3,5-Dichlorophenyl)succinimide (NDPS) induces nephrotoxicity via one or more metabolites which arise from oxidation of the succinimide ring. The purpose of this study was to examine the nephrotoxic potential of N-(3,5-dichlorophenyl)-3-hydroxysuccinamic acid (3-NDHSA), a potential metabolite of NDPS and a positional isomer of N-(3,5-dichlorophenyl)-2-hydroxysuccinamic acid (2-NDHSA), a known nephrotoxic metabolite of NDPS. Male Fischer 344 rats were administered a single intraperitoneal injection of 3-NDHSA (0.2 or 0.4 mmol/kg) or sesame oil (2.5 mmol/kg), and renal function was monitored at 24 and 48 h. Both doses of 3-NDHSA induced diuresis, increased proteinuria, glucosuria and hematuria, elevated blood urea nitrogen (BUN) concentrations and kidney weights, decreased organic ion accumulation by renal cortical slices, and induced proximal tubular necrosis. The characteristics of 3-NDHSA-induced nephrotoxicity were identical to NDPS-induced nephropathy, but were evident at lower doses with 3-NDHSA. These results demonstrate that 3-NDHSA is a nephrotoxicant which might contribute to NDPS-induced nephropathy.

journal_name

Toxicol Lett

journal_title

Toxicology letters

authors

Rankin GO,Shih H,Teets VJ,Nicoll DW,Brown PI

doi

10.1016/0378-4274(89)90047-7

subject

Has Abstract

pub_date

1989-09-01 00:00:00

pages

217-23

issue

3

eissn

0378-4274

issn

1879-3169

pii

0378-4274(89)90047-7

journal_volume

48

pub_type

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