Study on hepatotocicity of p-dichlorobenzene

对二氯苯的肝毒性研究

• 批准号: 04680077
• 负责人: MIZUTANI Tamio
• 金额: $ 1.22万
• 依托单位: Kyoto Prefectural University
• 依托单位国家: 日本
• 项目类别: Grant-in-Aid for General Scientific Research (C)
• 财政年份: 1992
• 资助国家: 日本
• 起止时间: 1992 至 1993
• 项目状态: 已结题
• 来源: https://kaken.nii.ac.jp/en/grant/KAKENHI-PROJECT-04680077/
• 关键词: hepatotoxicity; glutathione; rho-dichlorobenzene; phenol-quinone; metabolite; マウス

rho-Dichlorobenzene (rho-DCB) is widely used as a moth repellent, and a space deodorant. In mice pretreated with DL-buthionine sulfoximine (BSO ; 2mmol/kg or higher doses, i, p.), an inhibitor of glutathione (GSH) synthesis, administration of rho-DCB (100-400mg/kg, p.o.) resulted in dose-dependent hepatotoxicity as judged by increased serum alanine aminotransferase (ALT) activities and liver calcium concentrations and by histologic examination of the liver. rho-DCB alone (up to 1200mg/kg) resulted in no hepatotoxicity. Administration of GSH monoethyl ester, which is known as a useful means for increasing organ GSH levels, protected against the hepatotoxicity caused by rho-DCB in combination with BSO.Treatment with inhibitors of hepatic cytochrome rho-450-dependent monooxygenases, carbon disulfide, metyrapone, and piperonyl butoxide, also prevented the hepatotoxicity. These results suggest that rho-DCB is activated by a cytochrome rho-450-dependent metabolic reaction and that the hepatotoxicity is caused by inadequate rates of detoxification of the resulting metamolite in mice depleted of hepatic GSH by BSO treatment. The liver injury was preceded by an extensive depletion of hepatic GSH but not accompanied by significant changes in hepatic contents of lipid peroxides and protein thiols.

rho-二氯苯 (rho-DCB) 广泛用作防蛀剂和太空除臭剂。在用谷胱甘肽 (GSH) 合成抑制剂 DL-丁硫氨酸亚磺酰亚胺（BSO；2mmol/kg 或更高剂量，i, p.）预处理的小鼠中，给予 rho-DCB（100-400mg/kg，口服）会导致剂量依赖性肝毒性，这通过血清丙氨酸转氨酶 (ALT) 活性增加来判断。 肝脏钙浓度和肝脏组织学检查。单独使用 rho-DCB（高达 1200mg/kg）不会导致肝毒性。施用 GSH 单乙酯被认为是增加器官 GSH 水平的有用方法，可防止 rho-DCB 与 BSO 组合引起的肝毒性。使用肝细胞色素 rho-450 依赖性单加氧酶抑制剂、二硫化碳、美替拉酮和胡椒基丁醚进行治疗也可预防肝毒性。这些结果表明，rho-DCB 是由细胞色素 rho-450 依赖性代谢反应激活的，并且肝毒性是由 BSO 治疗耗尽肝脏 GSH 的小鼠中所产生的代谢物解毒速率不足引起的。肝损伤之前，肝脏 GSH 大量消耗，但肝脏脂质过氧化物和蛋白硫醇含量不发生显着变化。

项目成果

Tamio Mizutani, Yoshiko Nakahori, and Kei-ichi Yamamoto: "rho-Dichlorobenzene-induced hepatotoxcity in mice depleted of GSH by treatment with BSO" Toxicology. 90(in print). (1994)

Tamio Mizutani、Yoshiko Nakahori 和 Kei-ichi Yamamoto：“用 BSO 治疗耗尽 GSH 的小鼠中，rho-二氯苯诱导的肝毒性”毒理学。

Tamio Mizutani et al: "p-Dichlorobenzene-induced hepatotoxicity in mice depleted of GSH by treatment with BSO" Toxicology. 90. (1994)

Tamio Mizutani 等人：“通过 BSO 治疗耗尽 GSH 的小鼠中对二氯苯诱导的肝毒性”。

Tamio Mizutani et al.: "p-Dichlorobenzene-induced hepatotoxicity in mice depleted of GSH by treatment with BSO" Toxicology. 90. (1994)

Tamio Mizutani 等人：“通过 BSO 治疗耗尽 GSH 的小鼠中对二氯苯诱导的肝毒性”。