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首页> 外文期刊>Archives of Toxicology >Inhibitory effects of KAT-681, a liver-selective thyromimetic, on development of hepatocellular proliferative lesions in rats induced by 2-acetylaminofluorene and partial hepatectomy after diethylnitrosamine initiation.
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Inhibitory effects of KAT-681, a liver-selective thyromimetic, on development of hepatocellular proliferative lesions in rats induced by 2-acetylaminofluorene and partial hepatectomy after diethylnitrosamine initiation.

机译：KAT-681（一种肝选择性甲状腺激素）对二乙酰基亚硝胺引发的2-乙酰氨基芴和部分肝切除术诱导的大鼠肝细胞增殖性损伤的抑制作用。

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To examine the potential inhibitory effects of a novel liver-selective thyromimetic, KAT-681 (KAT), on the development of hepatocellular proliferative lesions, male F344 rats were given a single intraperitoneal injection of 150 mg/kg diethylnitrosamine (DEN), followed by gavage administration of 7.5 mg/kg per day of 2-acetylaminofluorene (2-AAF) twice daily from weeks 2 to 4 with partial hepatectomy (PH) at week 3. From 5 weeks after the completion of 2-AAF administration, the rats were orally dosed with 0.04, 0.1, or 0.25 mg/kg per day KAT for 3 weeks, and subjected to morphometric analysis of the induced glutathione S-transferase placental form (GST-P)-positive lesions and hepatocellular adenomas (HCAs). Administration of KAT significantly and dose-dependently reduced the total area of GST-P-positive lesions (by 34-48%) and also their numbers (by 20-44%), their mean size not being significantly changed. No effects on the number of HCAs were apparent, although a reduction in their mean size was detected at a dose of 0.25 mg/kg per day KAT (by 34%). On biochemical analysis, serum activity of gamma-glutamyl transpeptidase, an enzyme related to hepatocarcinogenesis, was markedly reduced in rats given 0.25 mg/kg per day KAT (by 64%). The results of the present study thus suggest that KAT inhibits the development of altered hepatocellular foci and might be a promising chemopreventive agent for hepatocarcinogenesis.
机译：为了检查新型肝选择性胸苷药KAT-681（KAT）对肝细胞增殖性病变发展的潜在抑制作用，对雄性F344大鼠进行了一次腹膜内注射150 mg / kg二乙基亚硝胺（DEN）的治疗，从第2周到第4周每天两次灌胃每天7.5 mg / kg的2-乙酰氨基芴（2-AAF），在第3周进行部分肝切除术（PH）。从完成2-AAF给药后的5周，大鼠每天口服0.04、0.1或0.25 mg / kg KAT，持续3周，并对诱导的谷胱甘肽S-转移酶胎盘形式（GST-P）阳性病变和肝细胞腺瘤（HCA）进行形态分析。施用KAT可以显着且剂量依赖性地减少GST-P阳性病变的总面积（减少34-48％）以及其数量（减少20-44％），其平均大小没有明显改变。尽管以每天0.25 mg / kg的KAT剂量检测到它们的平均大小有所减少（降低了34％），但对HCA数量没有明显影响。根据生化分析，在每天给予0.25 mg / kg KAT的大鼠中，γ-谷氨酰转肽酶（一种与肝癌发生有关的酶）的血清活性明显降低（降低了64％）。因此，本研究的结果表明，KAT可以抑制肝细胞灶改变的发生，并且可能是有希望的肝癌发生化学预防剂。

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