Heme oxygenase-1 alleviates alcoholic liver steatosis: histopathological study

Abstract

Excessive alcohol consumption is one of the most important causes of hepatic steatosis, which involves oxidative stress. In particular, increased oxidative stress has been strongly linked to stimulation of the expression of heme oxygenase-1 (HO-1). This study aimed to investigate whether HO-1 could alleviates alcoholic steatosis in rats. Male Wistar rats were randomly divided into 4 groups: 1) the control group, 2) the EtOH group, 3) the EtOH + ZnPP-IX group and 4) the EtOH + Hemin group. Liver histopathology was investigated in weeks 1 and 4 after the start of the treatment period. Alcohol treatment significantly increased the hepatic malondialdehyde (MDA) levels, an oxidative stress marker. In addition, it increased the triglyceride, alanine aminotransferase (ALT) and aspartate aminotransferase (AST) levels in both weeks. Gross examination demonstrated a yellowish and slightly enlarged liver in the alcohol-treated rats. Hematoxylin and eosin (H&E) and Oil Red O staining indicated hepatic steatosis, which was characterized by diffuse, extensive fatty accumulation and discrete lipid droplets of variable size in hepatocytes of the alcohol-treated rats. Administration of the HO-1 inducer hemin resulted in upregulation of hepatic HO-1 gene expression, reduced the MDA, triglyceride, ALT and AST levels and alleviated alcoholic hepatic steatosis, whereas administration of the HO-1 inhibitor zinc protoporphyrin IX (ZnPP-IX) resulted in downregulation of hepatic HO-1 gene expression and could not alleviate alcoholic hepatic steatosis either week. In conclusion, HO-1 could alleviate alcoholic hepatic steatosis in male Wistar rats and may be useful in development of a new therapeutic approach.

Effect of iron on cholesterol 7α-hydroxylase expression in alcohol-induced hepatic steatosis in mice

“…Among various genes encoding for anti-oxidative and anti-inflammatory proteins, haem oxygenase-1 (HO-1) is particularly attractive. In a previous study, HO-1 expression could be induced by alcohol consumption in mice (47). HO-1 is an anti-inflammatory molecule that oxidizes heme to biliverdin, CO, and free iron (48)(49)(50).…”

Effect of a heme oxygenase-1 inducer on NADPH oxidase expression in alcohol-induced liver injury in male Wistar rats

“…Recently, Palipoch et al demonstrated that ethanol treatment of male Wistar rats by gavage for 4 weeks can induce fatty liver, with elevated levels of oxidative stress biomarker. This indicates oxidative stress is an important mechanism in inducing alcoholinduced liver injury [9].…”

“…Oxidative stress can cause increased expression of heme oxygenase-1 (HO-1) levels [8]. Recently, Palipoch et al demonstrated that HO-1 inducer hemin can relieve alcohol-induced liver injury, especially hepatic steatosis [9]. However, the underlying mechanisms of hemin remain unclear.…”

Protective effect of Letinous�edodes foot peptides against ethanol‑induced liver injury in L02 cells

“…Alcoholic liver disease (ALD), which is mainly caused by excessive alcohol drinking, endangers human health worldwide (1). Individuals with ALD that progress to advanced disease stages with liver fibrosis and cirrhosis have increased risk of complications such as portal hypertension, liver cancer and liver failure (2).…”