Hepatocellular accumulation of poly(ADP-ribose) in male ICR mice treated with a necrogenic dose of carbon tetrachloride.

Research communications in molecular pathology and pharmacology Pub Date : 2003-01-01

Phi-Huynh Su, Masanori Takehashi, Seigo Tanaka, Marek Banasik, Todd Stedeford, Kunihiro Ueda, Carlos Muro-Cacho, Raymond D Harbison

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Abstract

Overactivation of poly(ADP-ribose) polymerase-1 (PARP-1) in response to oxidative stress has been shown to contribute to necrotic cell death by consuming NAD+ and ATP. In the present study, PARP-1 overactivation was determined by identifying the distribution and accumulation of poly(ADP-ribose) following intraperitoneal administration of a hepatotoxic dose of carbon tetrachloride (572 mg/kg). Treated animals exhibited lipid peroxide levels 16.5-fold higher than controls. Serum activities of glutamic pyruvic transaminase and glutamic oxaloacetic transaminase were increased by 6.1-fold and 22.8-fold, respectively. Lactate dehydrogenase activity was significantly increased by 1.2-fold. Histopathological analyses revealed severe necrosis and increased poly(ADP-ribsyl)ation of cells in the centrilobular region of treated animals versus saline controls. These results demonstrate the role of PARP-1 overactivation in chemical-induced pathologies and suggest the potential role of PARP-1 inhibitors at preventing toxicity.

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四氯化碳致坏死剂量处理的雄性ICR小鼠肝细胞聚腺苷核糖的积累。

在氧化应激反应中，聚(adp -核糖)聚合酶-1 (PARP-1)的过度激活通过消耗NAD+和ATP导致坏死细胞死亡。在本研究中，通过鉴定四氯化碳(572 mg/kg)腹腔内肝毒性剂量后聚(adp -核糖)的分布和积累来确定PARP-1过度激活。处理过的动物的脂质过氧化水平比对照组高16.5倍。血清谷丙转氨酶和谷草转氨酶活性分别提高了6.1倍和22.8倍。乳酸脱氢酶活性显著提高1.2倍。组织病理学分析显示，与生理盐水对照相比，治疗动物小叶中央区域的细胞严重坏死和多肽核糖基化增加。这些结果证明了PARP-1过度激活在化学诱导病理中的作用，并提示PARP-1抑制剂在预防毒性方面的潜在作用。

本文章由计算机程序翻译，如有差异，请以英文原文为准。

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Research communications in molecular pathology and pharmacology

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