Dietary Iron Overload Abrogates Chemically-Induced Liver Cirrhosis in Rats.
Dietary Iron Overload Abrogates Chemically-Induced Liver Cirrhosis in Rats.
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DOI：
10.3390/nu10101400
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发表时间：
2018-10-02
期刊：
影响因子：
5.9
通讯作者：
Yamate J
中科院分区：
文献类型：
--
作者：
Atarashi M;Izawa T;Mori M;Inai Y;Kuwamura M;Yamate J
慢性肝病是一种难治性疾病，可发展为肝硬化和肝细胞癌。肝铁超载被认为参与慢性肝病的进展；然而，其机制仍有待阐明。本研究采用化学诱导肝硬化模型，探讨膳食铁超载的作用。大鼠分别饲喂高铁或标准饮食，每周2次腹腔注射硫乙酰胺（TAA）或生理盐水，连续20周。TAA治疗大鼠（TAA组）出现以持续肝细胞损伤、单核细胞炎症和桥性纤维化为特征的进行性肝硬化；铁喂养和TAA治疗（Fe-TAA组）大鼠的这些病变明显减轻。单独给铁（铁组）大鼠无肝损伤迹象。与TAA组相比，Fe-TAA组肝脏中cleaved caspase-3的表达降低，而磷酸化rip3的表达不降低。Fe-TAA组tunel阳性（末端脱氧核苷酸转移酶dUTP缺口末端标记）凋亡的肝细胞数量低于TAA组。肝脏异种代谢和脂质过氧化与肝硬化的消除关系不大。我们的研究结果表明，饮食中的肝铁超载可以消除大鼠化学诱导的肝硬化，这可能部分涉及减少肝细胞凋亡。
Chronic liver disease is an intractable disease, which can progress to cirrhosis and hepatocellular carcinoma. Hepatic iron overload is considered to be involved in the progression of chronic liver diseases; however, the mechanism remains to be elucidated. Here we investigate the role of dietary iron overload using chemically-induced liver cirrhosis model. Rats were fed a high-iron or standard diet and were injected intraperitoneally with thioacetamide (TAA) or saline twice a week for 20 weeks. Rats with TAA treatment (TAA group) had progressive liver cirrhosis characterized by persistent hepatocellular injury, mononuclear cell inflammation and bridging fibrosis; these lesions were markedly reduced in rats with iron feeding and TAA treatment (Fe-TAA group). Rats with iron feeding alone (Fe group) had no evidence of liver injury. Hepatic expression of cleaved caspase-3, but not phospho-RIP3, was decreased in Fe-TAA group compared with that in TAA group. The number of TUNEL-positive (terminal deoxynucleotidyl transferase dUTP nick end labeling) apoptotic hepatocytes was lower in the Fe-TAA group than in the TAA group. Hepatic xenobiotic metabolism and lipid peroxidation were shown to be less related to the abrogation of liver cirrhosis. Our results suggested that dietary hepatic iron overload abrogates chemically-induced liver cirrhosis in rats, which could partly involve decreased hepatocellular apoptosis.
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影响因子：
29.4
作者：
Lambrecht RW;Sterling RK;Naishadham D;Stoddard AM;Rogers T;Morishima C;Morgan TR;Bonkovsky HL;HALT-C Trial Group
通讯作者：
HALT-C Trial Group
影响因子：
25.7
作者：
Guyader, Dominique;Thirouard, Anne-Sophie;Deugnier, Yves
通讯作者：
Deugnier, Yves
影响因子：
13.5
作者：
Maliken, Bryan D.;Nelson, James E.;Klintworth, Heather M.;Beauchamp, Mary;Yeh, Matthew M.;Kowdley, Kris V.
通讯作者：
Kowdley, Kris V.
DOI：
10.12659/msm.896494
发表时间：
2016-06-22
期刊：
Medical science monitor : international medical journal of experimental and clinical research
影响因子：
--
作者：
Milic S;Mikolasevic I;Orlic L;Devcic E;Starcevic-Cizmarevic N;Stimac D;Kapovic M;Ristic S
通讯作者：
Ristic S
影响因子：
13.5
作者：
Heimbach, Julie K.;Kulik, Laura M.;Marrero, Jorge A.
通讯作者：
Marrero, Jorge A.