Nephrotoxicosis in the Swiss ICR mouse and the Mongolian gerbil induced by 2-bromoethylamine hydrobromide
Abstract
Nephrotoxicosis induced by 2-bromoethylamine hydrobromide (BEA) as a model of renal papillary necrosis (RPN) was studied in the Swiss ICR mouse and Mongolian gerbil. Dose-response and sequential light and electron microscopic studies were performed in Swiss ICR mice. Male Swiss ICR mice were treated with BEA and water deprivation, 5% dextrose in water, dimethyl sulfoxide, piperonyl butoxide, SKF-525A, sodium phenobarbital, beta-naphthoflavone, probenecid, reserpine, diethyl maleate, buthionine sulfoximine or L-cysteine. Bromoethylamine principally produced proximal tubular necrosis (TN) in Swiss ICR mice that developed in a dose-dependent manner and was more severe in male than female mice. Light microscopic lesions at 2 hours post-treatment were degeneration of proximal tubular epithelium and ultrastructural alterations at 5 minutes post-treatment included cytoplasmic vacuolation of proximal tubule epithelium and degeneration of glomerular, peritubular and vasa recta capillary endothelium. Water deprivation, diuresis, dimethyl sulfoxide, piperonyl butoxide, SKF-525A, sodium phenobarbital and beta-naphthoflavone did not alter the development of BEA-induced TN in mice. Probenecid decreased the severity of TN and reserpine inhibited TN development. Tissue glutathione depletion increased the sensitivity of mice to BEA and L-cysteine decreased the severity of BEA-induced TN. Sequential light and electron microscopic studies were performed in Mongolian gerbils. Male Mongolian gerbils treated with BEA were also treated with diuresis, piperonyl butoxide or reserpine. Bromoethylamine produced RPN in the Mongolian gerbil that was equally severe in males and females. Light microscopic lesions at 6 hours post-treatment were congestion of the proximal vasa recta by aggregates of platelets and erythrocytes and ultrastructural alterations at 2 hours post-treatment were degeneration of vasa recta endothelium and inner medullary interstitial edema. Diuresis and piperonyl butoxide did not effect RPN development in the gerbil, but, reserpine did inhibit RPN development. Bromoethylamine-induced TN in the Swiss ICR mouse is due to direct cytotoxicity, ischemia and peroxidative injury whereas, BEA-induced RPN in the Mongolian gerbil is due to ischemia. The mixed function oxidase system is not involved in the production of renal lesions in the mouse and gerbil. Renal vasodilation inhibits the development of BEA-induced renal lesions. In the mouse, BEA is concentrated within tubule epithelium by organic anion transport and an adequate renal sulfhydral concentration is necessary to prevent BEA-induced TN.
Degree
Ph.D.
Advisors
Carlton, Purdue University.
Subject Area
Animal diseases|Veterinary services|Pathology
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