Characteristics of Bromate-induced Acute Renal Failure in Rats

Shin, Seok Joon; Park, Ho Seon; Choi, Young Jin; Yang, Chul Woo; Jin, Dong Chan; Kim, Yong Soo; Kim, Jin; Chang, Yoon Sik; Bang, Byung Kee

Abstract

BACKGROUND
Bromate has been reported to cause hemolytic anemia, acute renal failure, hearing and visual impairments. Several mechanisms for bromate-induced renal damage have been suggested including direct tubular toxicity due to induction of active oxygen radicals. However, the mechanism has not been clearly determined. The purpose of this study was to analyze the clinical characteristics of acute renal failure and renal tissue injuries following bromate intoxication. METHODS: Sprague-Dawley rats were intraperitoneally treated with potassium bromate 75 mg/kg (B75) or 150 mg/kg (B150). Blood urea nitrogen, serum creatinine, 24 hours urine volume, and creatinine clearance rate were measured at 24 hours, 48 hours, 1 week and 2 weeks after bromate injection. Light microscopic findings and the expressions of Na+ - K+ - ATPase-alpha 1 and aquaporin-2 in renal tissues were examined by PAS stain and immunohistochemical stain. RESULTS: Potassium bromate induced acute renal failure. In B75, acute renal failure was recovered after 1 week. However, in B150, all rats were dead in 48 hours due to severe uremia. Light microscopic examination revealed severe acute tubular necrosis in B75 and B150, which was severer in B150 compared to B75, and was more prominent in the tubules of the inner strip of outer medulla compared to cortex. Na+ - K+ - ATPase-alpha 1 expression was not changed in the renal cortex after bromate treatment. However, the expression was slightly decreased in the inner strip of outer medulla at 48 hours and recovered at 2 weeks in B75, and it was severely decreased at 24 and 48 hours in B150. The expression of aquaporin-2 in the inner strip of outer medulla was increased in B75 and was decreased in B150. CONCIUSION: Bromate induced acute tubular necrosis in inner strip of outer medulla of the kidney. Low dose bromate induced the decreased expressions of Na+ - K+ - ATPase-alpha 1, which lead to polyuric acute renal failure, but high dose bromate induced severe acute tubular necrosis, which lead to severe oliguric acute renal failure.