Amelioration of diet-induced nonalcoholic steatohepatitis in rats by Mn-salen complexes via reduction of oxidative stress

Abstract

Background: 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. Methods: 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. Results: 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. Conclusion: 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.

Effect of Pioglitazone, Quercetin, and Hydroxy Citric Acid on the Lipid Profile and Lipoproteins in Experimentally Induced Non-alcoholic Steatohepatitis (NASH)

“…44 As a multifunctional lipoprotein, HDL-C possess antioxidant and antiinflammatory activities. 45 (-)-HCA is a potent inhibitor of ATP citrate lyase, which catalyses the extra mitochondrial cleavage of citrate to oxaloacetate and acetyl-CoA. The inhibition of this reaction limits the availability of acetyl-CoA units required for fatty acid synthesis and lipogenesis during a lipogenic diet, that is, a diet high in carbohydrates.…”

Dietary Egg Yolk Supplementation Improves Low-Protein-Diet-Induced Fatty Liver in Rats

“…Although there is no report about amelioration of low-protein-induced fatty liver by antioxidant as far as our bibliographic survey could uncover, it has been reported that lowprotein diets induced fatty liver along with an increase in hepatic oxidative stress (48,49). Antioxidative components have been used for treatment of non-alcoholic fatty liver disease (50,51). Therefore, phosphopeptides derived from phosvitin can eliminate hepatic oxidative stress to ameliorate the fatty liver.…”

Intrahepatic transplantation of adipose-derived stem cells attenuates the progression of non-alcoholic fatty liver disease in rats

“…; Merck Chemicals, Shanghai, China), and the adipose tissues (~3x1.5x0.5 cm) were collected by excision from the subcutaneous inguinal region of male Sprague-Dawley rats, and washed thoroughly with phosphate-buffered saline (PBS; GE Healthcare Life Sciences, Logan, UT, USA). Subsequently, the tissues were cut into small sections (~0.1mm 3 ) and digested with 0.1% type I collagenase (Sigma-Aldrich, St. Louis, MO, USA) at 37˚C with gentle agitation for 60 min. Subsequently, the type I collagenase activity was neutralized by adding an equal volume (10 ml per rat) of α-modified Eagle's minimum essential medium (α-MEM; GE Healthcare Life Sciences) containing 20% fetal bovine serum (FBS; Gibco Life Technologies, Carlsbad, CA, USA), followed by filtering through an 100 µm cell strainer and centrifugation at 400 x g for 10 min at room temperature.…”