Abstract

Nonalcoholic steatohepatitis (NASH) progresses from nonalcoholic fatty liver disease (NAFLD); however, efficacious drugs for NASH treatment are lacking. Sodium alginate (SA), a soluble dietary fiber extracted from brown algae, could protect the small intestine from enterobacterial invasion. NASH pathogenesis has been suggested to be associated with enterobacterial invasion, so we examined the effect of SA on methionine- and choline-deficient (MCD) diet-induced steatohepatitis in mice (the most widely-used model of NASH). The mice (n = 31) were divided into three groups (mice fed with regular chow, MCD diet, and MCD diet premixed with 5% SA) for 4 and 8 weeks. The MCD diet increased lipid accumulation and inflammation in the liver, the NAFLD Activity Score and hepatic mRNA expression of tumor necrosis factor-α and collagen 1α1, and induced macrophage infiltration. Villus shortening, disruption of zonula occludens-1 localization and depletion of mucus production were observed in the small intestine of the MCD-group mice. SA administration improved lipid accumulation and inflammation in the liver, and impaired barrier function in the small intestine. Collectively, these results suggest that SA is useful for NASH treatment because it can prevent hepatic inflammation and fatty degeneration by maintaining intestinal barrier function.

Highlights

  • The number of patients with nonalcoholic fatty liver disease (NAFLD) has increased worldwide, possibly in accordance with the global increase in obesity

  • We examined the effects of Sodium alginate (SA) on methionine- and choline-deficient (MCD) diet-induced steatohepatitis

  • The NAS were significantly higher in the MCD group than that in the control group (p < 0.01), and the NAS was significantly lower in the MCD + SA group than that in the MCD group (p < 0.01, Figure 1B)

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Summary

Introduction

The number of patients with nonalcoholic fatty liver disease (NAFLD) has increased worldwide, possibly in accordance with the global increase in obesity. Nonalcoholic steatohepatitis (NASH) is a disease state that progresses from NAFLD. NASH is characterized by steatosis, inflammation, and ballooning degeneration of hepatocytes [1]. NASH has received considerable attention because it can progress to liver cirrhosis and hepatocellular carcinoma [2]. The pathogenesis of NASH is not known, but genetic factors, changes in intestinal bacterial flora, inflammation, and oxidative stress have been implicated [3,4]. Mar. Drugs 2019, 17, 104; doi:10.3390/md17020104 www.mdpi.com/journal/marinedrugs

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