Nephrotoxic effect of subchronic exposure to S-(1,2-dichlorovinyl)-L-cysteine in mice

• Published in: Journal of toxicological sciences Vol. 37; no. 5; pp. 871 - 878
• Main Authors: Shirai, Nobuaki, Ohtsuji, Mareki, Hagiwara, Keitaro, Tomisawa, Hiroki, Ohtsuji, Naomi, Hirose, Sachiko, Hagiwara, Hiromi
• Format: Journal Article
• Language: English
• Published: Japan The Japanese Society of Toxicology 2012; Japan Science and Technology Agency
• Subjects: Animals; Blood; Blood Urea Nitrogen; Cox-2; Cyclooxygenase 2 - genetics; Cyclooxygenase-2; Cysteine - analogs & derivatives; Cysteine - toxicity; DCVC; Degeneration; Fibrosis; Fibrosis - chemically induced; Interleukin 6; Interleukin-6 - genetics; Kidney; Kidney - drug effects; Kidney - metabolism; Kidney - pathology; Male; Metabolites; Mice; Mice, Inbred BALB C; mRNA; Necrosis - chemically induced; Nitrogen; Organ Size - drug effects; Polymerase chain reaction; Renal failure; Renal function; RNA, Messenger - metabolism; Solvents; TNF-α; Toxicity; Trichloroethylene; Tumor necrosis factor- alpha; Tumor Necrosis Factor-alpha - genetics; Tumors; Urea
• ISSN: 0388-1350; 1880-3989
• DOI: 10.2131/jts.37.871

The effect of subchronic exposure of S-(1,2-dichlorovinyl)-L-cysteine (DCVC), an active metabolite of trichloroethylene (TCE), was investigated in mice, as a part of mechanistic assessment of renal toxicity of TCE. To examine the subchronic effects of DCVC on kidney function, Balb/c male mice were administered DCVC orally and intraperitoneally once a week for 13 weeks at 1, 10 and 30 mg/kg (Main Study) and for 8 weeks at 30 mg/kg (PCR Study). At the terminal sacrifice, mice orally and intraperitoneally administered with 10 and 30 mg/kg showed significantly lower kidney weight and significantly higher blood urea nitrogen levels than the control group. Pathological examination revealed that a dose of 30 mg/kg delivered by both routes resulted in renal tubular degeneration characterized by tubular necrosis and interstitial fibrosis, and in degradation of the cortex. Degenerative changes were accompanied by the increased expression of tumor necrosis factor-α, interleukin-6 and cyclooxygenase-2 mRNAs in the kidney of mice treated with 30 mg/kg for 8 weeks. These pathohistological observations mostly corresponded to those in short-term toxicity studies on DCVC. DCVC might be a direct cause of renal toxicity, which is suggested from the aggravation in these symptoms with the dose increase.