Abstract
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.
Highlights
Cirrhosis is an intractable, advanced liver disease resulting from chronic liver diseases (CLD) such as viral hepatitis, alcoholic hepatitis and non-alcoholic steatohepatitis
Our results suggested that dietary hepatic iron overload abrogates chemically-induced liver cirrhosis in rats, which could partly involve decreased hepatocellular apoptosis
In the present study we investigated the possibility of the involvement of metabolism enzymes in the abrogation of TAA-induced liver cirrhosis
Summary
Cirrhosis is an intractable, advanced liver disease resulting from chronic liver diseases (CLD) such as viral hepatitis, alcoholic hepatitis and non-alcoholic steatohepatitis. Global liver cirrhosis deaths were more than one million in 2010 [2]. Liver cirrhosis is a significant global health burden. Iron is an essential micronutrient for all living organisms. It has important roles in oxygen transport, oxidative phosphorylation, and other enzymatic functions [3,4]. Once iron exceeds the storage capacity of the body, excess iron can accumulate in the liver, heart and endocrine glands, leading to damage and/or dysfunction to these vital organs [5]. Hepatocytes produce hepcidin, the master regulator of systemic iron homeostasis. Repeated and/or persistent liver damage can perturb and decrease hepcidin production, resulting in secondary (acquired) iron overload [3,4,8]
Sign-in/Register to view highlights & summary Sign-in/Register to access full text options 
Talk to us
Join us for a 30 min session where you can share your feedback and ask us any queries you have
Schedule a callDisclaimer: All third-party content on this website/platform is and will remain the property of their respective owners and is provided on "as is" basis without any warranties, express or implied. Use of third-party content does not indicate any affiliation, sponsorship with or endorsement by them. Any references to third-party content is to identify the corresponding services and shall be considered fair use under The CopyrightLaw.
