Dietary iron overload inhibits carbon tetrachloride induced promotion in chemical hepatocarcinogenesis:: effects on cell proliferation, apoptosis, and antioxidation
Dietary iron overload inhibits carbon tetrachloride induced promotion in chemical hepatocarcinogenesis:: effects on cell proliferation, apoptosis, and antioxidation
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DOI：
10.1016/s0168-8278(99)80201-3
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发表时间：
1999-04-01
影响因子：
25.7
通讯作者：
Stål, P
中科院分区：
文献类型：
--
作者：
Wang, GS;Eriksson, LC;Stål, P
背景/目的：本研究的目的是研究羰基铁喂养是否会促进由二乙基亚硝胺（DEN）引发并由四氯化碳诱导的肝硬化促进的癌前病变的发展。方法：用含1.25%-2.5%羰基铁的饲料喂养雄性Wistar大鼠23周，并经胃内注射CCl_4（1.0或2.0 ml/kg/周）持续13周，随后一次腹腔注射DEN（200 mg/kg），之后再给予CCl 4 8周。首次注射CCl 4后48 h处死动物以评估肝坏死，8周后处死动物以评估纤维化，DEN后9周处死动物以确定谷胱甘肽S-转移酶7，7（GST-7，7）阳性灶的形成。铁治疗抵消了CCl 4给药后血清丙氨酸氨基转移酶水平升高和肝坏死，与对照组相比，用CCl 4处理的大鼠的肝脏还原Q9和α-生育酚水平升高，而用铁处理的大鼠的肝脏还原Q9和α-生育酚水平降低。铁治疗没有改变纤维化。DEN开始后9周，与对照组相比，用CCl_4处理的大鼠GST-7，7阳性灶的数量和体积密度显著增加，但与铁共同处理抑制了这种增加。铁对CCl 4染毒大鼠肝细胞S期细胞比例有明显的抑制作用。结论：羰基铁耗尽肝脏的抗氧化剂水平，它减少了四氯化碳诱导的坏死和细胞增殖，它增强了细胞凋亡，并没有促进纤维化。这些效应可以解释在本研究中羰基铁在DEN引发后对CCl 4诱导的促进作用的抑制。
Background/Aims: The aim of this study was to investigate if feeding with carbonyl iron would facilitate the development of preneoplastic lesions initiated by diethylnitrosamine (DEN) and promoted by CCl4-induced liver cirrhosis.Methods: Male Wistar rats were fed a diet with 1.25%-2.5% carbonyl iron for 23 weeks and received intragastric injections of CCl4 (1.0 or 2.0 ml/kg per week) for 13 weeks, followed by one i.p injection of DEN (200 mg/kg), after which CCl4 was administered for 8 additional weeks. Animals were killed 48 h after the first CCl4 injection to evaluate liver necrosis, 8 weeks later to evaluate fibrosis, and 9 weeks after DEN to determine formation of glutathione S-transferase 7,7 (GST-7,7) positive foci.Results: Treatment with iron counteracted the increased serum alanine aminotransferase levels and liver necrosis following CCl4 administration, Hepatic levels of reduced Q9 and alpha-tocopherol were elevated in rats treated with CCl4 and decreased in rats treated with iron compared to the controls. Fibrogenesis was not altered by iron treatment. Nine weeks after DEN initiation, the number and volume density of GST-7,7-positive foci in rats treated with CCl4 were significantly increased as compared with controls, but co-treatment with iron inhibited this increase, Apoptotic index was increased in iron-loaded livers, and labelling index (the fraction of S-phase hepatocytes) was decreased by cotreatment with iron in livers exposed to CCl4.Conclusion: Carbonyl iron depleted hepatic levels of antioxidants, it decreased CCl4-induced necrosis and cell proliferation, it enhanced apoptosis and did not facilitate fibrogenesis. These effects together may explain the suppression of CCl4-induced promotion after DEN initiation exerted by carbonyl iron in the present study.