抄録
DMAC are widely used industrially as a solvent. DMAC is taken into the body via the dermal and respiratory tract to cause dermatitis and liver dysfunction. However, the mechanism for the onset of liver failure has been reported is still unknown. In this study, we confirmed the occurrence of liver failure due to exposure, and thereby to elucidate the mechanism for its onset. ICR male mice were divided into four groups of six each and exposed to DMAC at 0, 10, 50, 250ppm for 6 h/day for 14 days by inhalation. At the end of exposure period, histopathological changes were investigation by H&E staining in livers. The histopathological change was evaluated scoring of liver cell necrosis, the degree of inflammation. The plasma and part of the liver were used for biochemical analysis. Exposure by inhalation DMAC, in the exposed group compared with the control group, increased plasma ALT, AST. In the 250ppm exposure group were observed significant large area of liver necrosis, and also, the exposed groups of 10ppm and 50ppm were observed liver necrosis. In addition, the inflammatory cells were observed by DMAC inhalation. In the 50 ppm and 250 ppm exposed groups showed higher 8-OHdG level, and also, HO-1- and NQO1-mRNA were increased by DMAC inhalation. The results showed that mRNA level and protein level of CYP2E1 were increased in dose-dependent manner in livers of mice after DMAC inhalation. These results suggest that increase the oxidative stress in the process of oxidative metabolism of DMAC via CYP2E1.
