Abstract
Nonalcoholic steatohepatitis (NASH), a progressive stage of nonalcoholic fatty liver disease (NAFLD), is characterized by steatosis (accumulation of triacylglycerols within hepatocytes) along with inflammation and ballooning degeneration. It has been suggested that oxidative stress may play an important role in the progress of NAFLD to NASH. The aim of present study was to determine whether antioxidant supplementations using EUK-8, EUK-134 and vitamin C could improve the biochemical and histological abnormalities associated with diet-induced NASH in rats. NASH was induced in male N-Mary rats by feeding a methionine - choline deficient (MCD) diet. The rats were fed either normal chow or MCD diet for 10 weeks. After NASH development, the MCD-fed rats were randomly divided into four groups of six: the NASH group that received MCD diet, the EUK-8 group which was fed MCD diet plus EUK-8, the EUK-134 group which was fed MCD diet plus EUK-134 and the vitamin C group which received MCD diet plus vitamin C. EUK-8, EUK-134 and vitamin C (30 mg/kg body weight/day) were administered by gavage for eight weeks. Treatment of MCD-fed rats with salens reduced the sera aminotransferases, cholesterol, low density lipoprotein contents, the extent of lipid peroxidation and protein carbonylation whereas the HDL-C cholesterol levels were significantly increased. In addition, EUK-8 and EUK-134 improved steatosis, ballooning degeneration and inflammation in liver of MCD-fed rats. Antioxidant (EUK-8, EUK-134 and vitamin C) supplementation reduces NASH-induced biochemical and histological abnormalities, pointing out that antioxidant strategy could be beneficial in treatment of NASH.
Highlights
Nonalcoholic steatohepatitis (NASH), a progressive stage of nonalcoholic fatty liver disease (NAFLD), is characterized by steatosis along with inflammation and ballooning degeneration
Weight and liver index The rats in NASH group showed a 12% decrease in body weight, but those in the normal diet group increased weight by 17%, whereas the body weights of the groups on EUK-8, EUK-134 and vitamin C increased by 10%, 15% and 8%, respectively
Histopathological analyses The histological studies of the liver samples from the control and the test groups were performed to investigate the occurrence of steatohepatitis
Summary
Nonalcoholic steatohepatitis (NASH), a progressive stage of nonalcoholic fatty liver disease (NAFLD), is characterized by steatosis (accumulation of triacylglycerols within hepatocytes) along with inflammation and ballooning degeneration. The incidence of oxidative stress has been reported to be high among patients with metabolic syndrome and NASH [5,6]. In these patients, superoxide dismutase activity, the serum vitamin C and a-tocopherol concentrations are low, whereas lipid peroxidation and protein carbonylation levels are high [7]. The protective effects of these antioxidants against oxidative stress-induced injuries have been reported in many in vitro and in vivo disease models, including, stroke, amyotrophic lateral sclerosis, Parkinson [13], excitotoxic neuronal injury [14] and adult respiratory distress syndrome [15]
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