Depletion of Kupffer cell function by gadolinium chloride attenuates thioacetamide-induced hepatotoxicity -: Expression of metallothionein and HSP70
Depletion of Kupffer cell function by gadolinium chloride attenuates thioacetamide-induced hepatotoxicity -: Expression of metallothionein and HSP70
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DOI：
10.1016/s0006-2952(03)00443-x
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发表时间：
2003-09-15
影响因子：
5.8
通讯作者：
Cascales, M
中科院分区：
文献类型：
--
作者：
Andrés, D;Sánchez-Reus, I;Cascales, M
库普弗细胞功能在药物性肝损伤中起重要作用。因此，氯化钆（GD）通过选择性灭活库普弗细胞，可以减轻药物引起的肝毒性。通过对硫乙酰胺致肝坏死模型金属硫蛋白和热休克蛋白表达的影响，研究GD的作用。将GD （0.1 mmol/kg）预处理或未处理的大鼠腹腔注射硫乙酰胺（6.6 mmol/kg），于0、12、24、48、72和96 h取血和肝脏标本。测定肝损伤、库普弗细胞功能、微粒体FAD单加氧酶活性、氧化应激、金属硫蛋白和HSP70表达等相关指标。GD显著降低血清髓过氧化物酶活性和血清TNFalpha和IL-6浓度，硫乙酰胺使其升高。GD显著降低了坏死程度、氧化应激程度、脂质过氧化程度和微粒体FAD单加氧酶活性。与硫乙酰胺相比，GD诱导的金属硫蛋白和HSP70的表达发生了明显的变化。我们认为GD预处理可以减轻硫代乙酰胺诱导的肝损伤，提高金属硫蛋白和HSP70的表达。这种效应与血清细胞因子和髓过氧化物酶活性水平的降低平行，表明Kupffer细胞参与了硫代乙酰胺诱导的肝损伤，贡献程度约为50%。(C) 2003 Elsevier Inc.版权所有。
Kupffer cell function plays an important role in drug-induced liver injury. Thus, gadolinium chloride (GD), by selectively inactivating Kupffer cells, can alleviate drug-induced hepatotoxicity. The effect of GD was studied in reference to metallothionein and heat shock proteins expression in an in vivo model of liver necrosis induced by thioacetamide. Rats, pre-treated or not with GD (0.1 mmol/kg), were intraperitoneally injected with thioacetamide (6.6 mmol/kg), and samples of blood and liver were obtained at 0, 12, 24, 48, 72 and 96 hr. Parameters related to liver damage, Kupffer cell function, microsomal FAD monooxygenase activity, oxidative stress, and the expression of metallothionein and HSP70 were determined. GD significantly reduced serum myeloperoxidase activity and serum concentration of TNFalpha and IL-6, increased by thioacetamide. The extent of necrosis, the degree of oxidative stress and lipoperoxidation and microsomal FAD monooxygenase activity were significantly diminished by GD. The effect of GD induced noticeable changes in the expression of both metallothionein and HSP70, compared to those induced by thioacetamide. We conclude that GD pre-treatment reduces thioacetamide-induced liver injury and enhances the expression of metallothionein and HSP70. This effect, parallel to reduced levels of serum cytokines and myeloperoxidase activity, demonstrates that Kupffer cells are involved in thioacetamide-induced liver injury, the degree of contribution being approximately 50%. (C) 2003 Elsevier Inc. All rights reserved.