Amimoto T, Matsura T, Koyama S Y, Nakanishi T, Yamada K, Kajiyama G
Department of Internal Medicine, Hiroshima University School of Medicine, Japan.
Free Radic Biol Med. 1995 Aug;19(2):169-76. doi: 10.1016/0891-5849(94)00233-a.
This study was performed to determine whether oxidative stress contributed to the initiation or progression of hepatic injury produced by acetaminophen (APAP). Treatment of fasted mice with APAP (400 mg/kg, I.P.) led to hepatic injury as indicated by a marked elevation of plasma alanine aminotransferase (ALT). APAP caused an increased amount of thiobarbituric acid-reactive substance (TBARS), which was accompanied by a loss of reduced forms of coenzyme Q9 (CoQ9H2) and coenzyme Q10 (CoQ10H2) functioning as antioxidants. APAP also markedly decreased hepatic reduced glutathione (GSH) levels. Pretreatment with CoQ10 (5 mg/kg, I.V.) reduced hepatic TBARS levels to 30% and plasma ALT levels to 26% of placebo pretreatment levels without affecting hepatic GSH levels at 3 h of APAP treatment. alpha-Tocopherol (alpha-Toc) (20 mg/kg, I.V.) pretreatment also reduced hepatic TBARS levels to 13% and plasma ALT levels to 27% of placebo pretreatment levels without affecting hepatic GSH levels. These results suggest that oxidative stress followed by lipid peroxidation might play a role in the pathogenesis of APAP-induced hepatic injury, and pretreatment with lipid-soluble antioxidants such as CoQ10 and alpha-Toc can limit hepatic injury produced by APAP.
本研究旨在确定氧化应激是否促成对乙酰氨基酚（APAP）所致肝损伤的起始或进展。用APAP（400mg/kg，腹腔注射）处理禁食小鼠导致肝损伤，这可通过血浆丙氨酸转氨酶（ALT）的显著升高来表明。APAP导致硫代巴比妥酸反应性物质（TBARS）量增加，同时作为抗氧化剂的辅酶Q9（CoQ9H2）和辅酶Q10（CoQ10H2）的还原形式减少。APAP还显著降低肝脏还原型谷胱甘肽（GSH）水平。在APAP处理3小时时，用辅酶Q10（5mg/kg，静脉注射）预处理可将肝脏TBARS水平降至安慰剂预处理水平的30%，血浆ALT水平降至26%，而不影响肝脏GSH水平。α-生育酚（α-Toc）（20mg/kg，静脉注射）预处理也可将肝脏TBARS水平降至安慰剂预处理水平的13%，血浆ALT水平降至27%，而不影响肝脏GSH水平。这些结果表明，氧化应激继而脂质过氧化可能在APAP诱导的肝损伤发病机制中起作用，并且用辅酶Q10和α-Toc等脂溶性抗氧化剂预处理可限制APAP所致的肝损伤。
