Abstract
Non-alcoholic steatohepatitis (NASH) can cause liver cirrhosis and hepatocellular carcinoma (HCC), with cases increasing worldwide. To reduce the incidence of liver cirrhosis and HCC, NASH is targeted for the development of treatments, along with viral hepatitis and alcoholic hepatitis. Lactoferrin (LF) has antioxidant, anti-cancer, and anti-inflammatory activities. However, whether LF affects NASH and fibrosis remains unelucidated. We aimed to clarify the chemopreventive effect of LF on NASH progression. We used a NASH model with metabolic syndrome established using connexin 32 (Cx32) dominant negative transgenic (Cx32ΔTg) rats. Cx32ΔTg rats (7 weeks old) were fed a high-fat diet and intraperitoneally injected with dimethylnitrosamine (DMN). Rats were divided into three groups for LF treatment at 0, 100, or 500 mg/kg/day for 17 weeks. Lactoferrin significantly protected steatosis and lobular inflammation in Cx32ΔTg rat livers and attenuated bridging fibrosis or liver cirrhosis induced by DMN. By quantitative RT–PCR, LF significantly down-regulated inflammatory (Tnf-α, Il-6, Il-18, and Il-1β) and fibrosis-related (Tgf-β1, Timp2, and Col1a1) cytokine mRNAs. Phosphorylated nuclear factor (NF)-κB protein decreased in response to LF, while phosphorylated JNK protein was unaffected. These results indicate that LF might act as a chemopreventive agent to prevent hepatic injury, inflammation, and fibrosis in NASH via NF-κB inactivation.
Highlights
The development of non-alcoholic fatty liver disease (NAFLD) is associated with obesity and disorders of lipid metabolism in patients with metabolic syndrome
We initially investigated the safety and chemopreventive effect of LF on non-alcoholic steatohepatitis (NASH) in a
**** p < 0.0001 compared to the Control group. These results indicated that LF administration prevented the development of steatohepatitis and fibrosis without any adverse effects observed in a rat NASH model
Summary
The development of non-alcoholic fatty liver disease (NAFLD) is associated with obesity and disorders of lipid metabolism in patients with metabolic syndrome. With a global increase in recent years of the obese population, the number of cases of NAFLD has increased [1,2]. A global meta-analysis describes the prevalence of NAFLD worldwide, which is approximately 25%, with the highest rates of 31% and 32% occurring in. South America and the Middle East, respectively [3]. The concept of NAFLD is a broad spectrum of disease, ranging from simple steatosis without inflammation to non-alcoholic steatohepatitis (NASH) with chronic progressive inflammation and fibrosis. Continuous inflammation produces abundant inflammatory cytokines and accumulates reactive oxygen species (ROS) in the liver, leading to fibrosis. Once fibrosis develops to bridge cirrhosis, 4.0/)
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.
