S-(1,2-DICHLOROVINYL)-L-CYSTEINE-INDUCED NEPHROTOXICITY IN THE NEW-ZEALAND WHITE-RABBIT - CHARACTERIZATION OF PROTEINURIA AND EXAMINATION OF THE POTENTIAL ROLE OF OXIDATIVE INJURY

被引：5

作者：

DAVIS, JW ^{[1
]}

BLAKEMAN, DP ^{[1
]}

JOLLY, RA ^{[1
]}

PACKWOOD, WH ^{[1
]}

KOLAJA, GJ ^{[1
]}

PETRY, TW ^{[1
]}

机构：

[1] UPJOHN CO,UPJOHN LABS,INVEST TOXICOL,KALAMAZOO,MI 49001

来源：

TOXICOLOGIC PATHOLOGY | 1995年 / 23卷 / 04期

关键词：

SODIUM DODECYL SULFATE-POLYACRYLAMIDE GEL ELECTROPHORESIS (SDS-PAGE) ANTIOXIDANTS; LIPID PEROXIDATION; HISTOPATHOLOGY; CLINICAL CHEMISTRIES;

D O I：

10.1177/019262339502300405

中图分类号：

R36 [病理学];

学科分类号：

100104 ;

摘要：

S-(1,2-dichlorovinyl)-L-cysteine (DCVC)-induced nephrotoxicity in vivo was investigated in New Zealand White rabbits. A primary emphasis in these studies was further characterization of DCVC-induced nephrotoxicity using a variety of serum and urinary analytes, including sodium dodecyl sulfate-polyacrylamide gel electrophoresis (SDS-PAGE). Additionally, the role of oxidative injury was assessed to address the dichotomy between reports indicating that such a mechanism is important in vivo and those indicating that such mechanisms do not contribute substantially to the mechanism of effects observed in vitro. Urine was collected prior to and at 8 and 24 hr after iv administration of DCVC. Serum was collected 15 min prior to and 24 hr after DCVC administration. Rabbits were euthanized 24 hr post-DCVC administration, and kidneys were fixed in formalin and further processed for light microscopic examination. DCVC (10 mg/kg, iv) induced a 45-50-fold increase in total urinary protein excretion, a 10-15-fold increase in urinary N-acetyl-beta-D-glucosaminidase concentration, plus a marked glucosuria by 24 hr postadministration. Additionally, DCVC increased serum creatinine levels by about 2-fold, with a trend toward increased blood urea nitrogen. SDS-PAGE analysis of rabbit urine confirmed the clinical finding of marked proteinuria in DCVC-treated animals, which in contrast to previously reported data was due to the presence of both low and high molecular weight proteins. Antioxidants had no significant effect on DCVC-dependent renal injury, nor was there evidence for DCVC-induced lipid peroxidation, as measured by either thiobarbituric acid-reactive substances or a commercial assay for malondialdehyde and hydroxalkenals. These latter data are consistent with previously published in vitro evidence citing no major role for lipid peroxidation in DCVC-induced nephrotoxicity.

引用

页码：487 / 497

页数：11