AIM： To build up the research models of hepatic fibrosis in mice.METHODS： Inbred wild-type FVB/N mice were either treated with alpha-naphthyl-isothiocyanate （ANIT）, allyl alcohol （AA）,carbon tetrachloride （CCl4...AIM： To build up the research models of hepatic fibrosis in mice.METHODS： Inbred wild-type FVB/N mice were either treated with alpha-naphthyl-isothiocyanate （ANIT）, allyl alcohol （AA）,carbon tetrachloride （CCl4）, 3,5-diethoxycarbonyl-l,4-dihydrocollidine （DDC）, and silica, or subjected to common bile duct ligation （CBDL） to induce hepatic injury. Liver biopsies were performed every 4 wk to evaluate hepatic fibrosis over a period of 6 mo. Cumulative cirrhosis and survival curves were constructed by life table method and compared with Wilcoxon test.RESULTS： Under the dosages used, there was neither mortality nor cirrhosis in AA and silica-treated groups. DDC and ANIT caused cirrhosis within 4-12 and 12-24 wk, respectively.Both showed significantly faster cirrhosis induction at high dosages without significant alteration of survival. The duration for cirrhosis induction by CCl4 ranged from 4 to 20 wk, mainly dependent upon the dosage. However, the increase in CCl4 dosage significantly worsened survival. Intraperitoneal CCl4 administration resulted in better survival in comparison with garage administration at high dosage, but not at medium and low dosages. After CBDL, all the mice developed liver cirrhosis within 4-8 wk and then died by the end of 26 wk.CONCLUSION： CBDL and administrations of ANIT, CCl4, and DDC ensured liver cirrhosis. CBDL required the least amount of time in cirrhosis induction, but caused shortened lives of mice. It was followed by DDC and ANIT administration with favorable survival. As for CCl4, the speed of cirrhosis induction and the mouse survival depended upon the dosages and the administration route.展开更多
The liver is the main organ responsible for the metabolism of drugs and toxic chemicals, and so is the primary target organ for many organic solvents. Work activities with hepatotoxins exposures are numerous and, more...The liver is the main organ responsible for the metabolism of drugs and toxic chemicals, and so is the primary target organ for many organic solvents. Work activities with hepatotoxins exposures are numerous and, moreover, organic solvents are used in various industrial processes. Organic solvents used in different industrial processes may be associated with hepatotoxicity. Several factors contribute to liver toxicity; among these are: species differences, nutritional condition, genetic factors, interaction with medications in use, alcohol abuse and interaction, and age. This review addresses the mechanisms of hepatotoxicity. The main pathogenic mechanisms responsible for functional and organic damage caused by solvents are: inflammation, dysfunction of cytochrome P450, mitochondrial dysfunction and oxidative stress. The health impact of exposure to solvents in the workplace remains an interesting and worrying question for professional health work.展开更多
基金Supported by the Chang Gung Memorial Hospital, Taoyuan, Taiwan, China, CMRPG 33014, CMRPG 33063 and CMRP 800
文摘AIM： To build up the research models of hepatic fibrosis in mice.METHODS： Inbred wild-type FVB/N mice were either treated with alpha-naphthyl-isothiocyanate （ANIT）, allyl alcohol （AA）,carbon tetrachloride （CCl4）, 3,5-diethoxycarbonyl-l,4-dihydrocollidine （DDC）, and silica, or subjected to common bile duct ligation （CBDL） to induce hepatic injury. Liver biopsies were performed every 4 wk to evaluate hepatic fibrosis over a period of 6 mo. Cumulative cirrhosis and survival curves were constructed by life table method and compared with Wilcoxon test.RESULTS： Under the dosages used, there was neither mortality nor cirrhosis in AA and silica-treated groups. DDC and ANIT caused cirrhosis within 4-12 and 12-24 wk, respectively.Both showed significantly faster cirrhosis induction at high dosages without significant alteration of survival. The duration for cirrhosis induction by CCl4 ranged from 4 to 20 wk, mainly dependent upon the dosage. However, the increase in CCl4 dosage significantly worsened survival. Intraperitoneal CCl4 administration resulted in better survival in comparison with garage administration at high dosage, but not at medium and low dosages. After CBDL, all the mice developed liver cirrhosis within 4-8 wk and then died by the end of 26 wk.CONCLUSION： CBDL and administrations of ANIT, CCl4, and DDC ensured liver cirrhosis. CBDL required the least amount of time in cirrhosis induction, but caused shortened lives of mice. It was followed by DDC and ANIT administration with favorable survival. As for CCl4, the speed of cirrhosis induction and the mouse survival depended upon the dosages and the administration route.
文摘The liver is the main organ responsible for the metabolism of drugs and toxic chemicals, and so is the primary target organ for many organic solvents. Work activities with hepatotoxins exposures are numerous and, moreover, organic solvents are used in various industrial processes. Organic solvents used in different industrial processes may be associated with hepatotoxicity. Several factors contribute to liver toxicity; among these are: species differences, nutritional condition, genetic factors, interaction with medications in use, alcohol abuse and interaction, and age. This review addresses the mechanisms of hepatotoxicity. The main pathogenic mechanisms responsible for functional and organic damage caused by solvents are: inflammation, dysfunction of cytochrome P450, mitochondrial dysfunction and oxidative stress. The health impact of exposure to solvents in the workplace remains an interesting and worrying question for professional health work.
