Gadolinium chloride suppresses styrene-induced cytochrome P450s expression in rat liver
Gadolinium chloride suppresses styrene-induced cytochrome P450s expression in rat liver
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DOI：
10.2220/biomedres.28.323
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发表时间：
2007-12-01
影响因子：
1.2
通讯作者：
Sugiyama, Toshihiro
中科院分区：
文献类型：
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作者：
Hirasawa, Fujiko;Kawagoe, Masami;Sugiyama, Toshihiro
为了评估钆（Gd）对几种形式的细胞色素P450（P450）和抗氧化酶的表达的影响，我们用氯化钆（25 mg Gd/kg体重）处理大鼠4小时后苯乙烯（多P450诱导剂）治疗（600 mg/kg）。与苯乙烯单独处理相比，Gd处理显著抑制了苯乙烯诱导的细胞色素P4502 B1（CYP 2B 1）、CYP 2B 2、CYP 2 E1和CYP 3A 2 mRNA表达，分别为48.6%、69.8%、61.1%和38.5%，同时蛋白质表达分别降低了1.42%、31.2%、21.1%和21.1%。Gd抑制苯乙烯诱导的CYP 1A 2的表达，但仅在蛋白质水平。另一方面，苯乙烯处理引起还原型谷胱甘肽（GSH）的减少，以及脂质过氧化物和血清ALT和AST活性的增加，表明肝损伤的发生可能是由于苯乙烯诱导的氧化应激在大鼠肝脏。后处理Gd衰减这种苯乙烯引起的肝损伤。此外，细胞的抗氧化酶，如过氧化氢酶，铜锌超氧化物歧化酶（CuZnSOD）和谷胱甘肽过氧化物酶（GPX）的mRNA表达几乎没有改变苯乙烯和/或Gd处理。总之，Gd抑制苯乙烯诱导的表达不仅CYP 2B 1，但也有几种形式的P450在mRNA和蛋白质水平，沿着衰减苯乙烯引起的肝损伤。这些结果表明，Gd是一种化学预防剂，对肝损伤所造成的外源性需要生物转化。
To assess the effect of gadolinium (Gd) on the expression of several forms of cytochrome P450 (P450s) and antioxidant enzymes, we treated rats with gadolinium chloride (25 mg as Gd/kg body weight) 4 h after styrene (a multiple P450 inducer) treatment (600 mg/kg). Gd treatment significantly suppressed styrene-inducible cytochrome P4502B1 (CYP2B1), CYP2B2, CYP2E1, and CYP3A2 mRNA expressions to 48.6%, 69.8%, 61.1%, and 38.5%, accompanying with the reduction of proteins expression to 1.42%, 31.2%, 21.1% and 21.1%, respectively, compared with styrene alone treatment. Gd suppressed styrene-inducible CYP1A2 expression, but only at the protein level. On the other hand, styrene treatment caused a decrease in reduced form of glutathione (GSH), as well as increases in lipid peroxide and serum ALT and AST activities, suggesting the occurrence of hepatic damage probably due to styrene-induced oxidative stress in rat liver. Post-treatment of Gd attenuated this styrene-caused hepatic damage. Moreover, mRNA expressions of cellular antioxidant enzymes such as catalase, CuZn-superoxide dismutase (CuZnSOD) and glutathione peroxidase (GPX) were hardly changed by styrene and/or Gd treatment. In summary, Gd suppressed styrene-inducible expression of not only CYP2B1 but also several forms of P450 at both the mRNA and protein levels, along with attenuation of styrene-caused liver damage. These findings suggested that Gd is a chemo-preventive agent against hepatic damage caused by xenobiotics requiring biotransformation.