title: The effects of α-lipoic acid on liver oxidative stress and free fatty acid composition in methionine-choline deficient diet-induced NAFLD.
abstract: Development of nonalcoholic fatty liver disease (NAFLD) occurs through initial steatosis and subsequent oxidative stress. The aim of this study was to examine the effects of α-lipoic acid (LA) on methionine-choline deficient (MCD) diet-induced NAFLD in mice. Male C57BL/6 mice (n=21) were divided into three groups (n=7 per group): (1) control fed with standard chow, (2) MCD2 group--fed with MCD diet for 2 weeks, and (3) MCD2+LA group--2 weeks on MCD receiving LA i.p. 100 mg/kg/day. After the treatment, liver samples were taken for pathohistology, oxidative stress parameters, antioxidative enzymes, and liver free fatty acid (FFA) composition. Mild microvesicular hepatic steatosis was found in MCD2 group, while it was reduced to single fat droplets evident in MCD2+LA group. Lipid peroxidation and nitrosative stress were increased by MCD diet, while LA administration induced a decrease in liver malondialdehyde and nitrates+nitrites level. Similary, LA improved liver antioxidative capacity by increasing total superoxide dismutase (tSOD), manganese SOD (MnSOD), and copper/zinc-SOD (Cu/ZnSOD) activity as well as glutathione (GSH) content. Liver FFA profile has shown a significant decrease in saturated acids, arachidonic, and docosahexaenoic acid (DHA), while LA treatment increased their proportions. It can be concluded that LA ameliorates lipid peroxidation and nitrosative stress in MCD diet-induced hepatic steatosis through an increase in SOD activity and GSH level. In addition, LA increases the proportion of palmitic, stearic, arachidonic, and DHA in the fatty liver. An increase in DHA may be a potential mechanism of anti-inflammatory and antioxidant effects of LA in MCD diet-induced NAFLD.
authors: 1 Institute of Pathophysiology "Ljubodrag Buba Mihailović," Faculty of Medicine, University of Belgrade , Belgrade, Serbia .
authors: Milena N
authors: MN
authors: Stanković
authors: Dušan
authors: D
authors: Mladenović
authors: Milica
authors: M
authors: Ninković
authors: Ivana
authors: I
authors: Ethuričić
authors: Slađana
authors: S
authors: Sobajić
authors: Bojan
authors: B
authors: Jorgačević
authors: Silvio
authors: S
authors: de Luka
authors: Rada Jesic
authors: RJ
authors: Vukicevic
authors: Tatjana S
authors: TS
authors: Radosavljević
mesh_terms: D000818:Animals; D002794:Choline / Q000009:adverse effects* / Q000032:analysis; D004032:Diet / Q000009:adverse effects*; D005230:Fatty Acids, Nonesterified / Q000737:chemistry* / Q000378:metabolism; D005234:Fatty Liver / Q000188:drug therapy* / Q000378:metabolism*; D006801:Humans; D015227:Lipid Peroxidation; D008099:Liver / Q000187:drug effects / Q000378:metabolism; D008297:Male; D008715:Methionine / Q000009:adverse effects* / Q000032:analysis; D051379:Mice; D008810:Mice, Inbred C57BL; D065626:Non-alcoholic Fatty Liver Disease; D018384:Oxidative Stress / Q000187:drug effects; D008063:Thioctic Acid / Q000008:administration & dosage*
chemical_list: D005230:Fatty Acids, Nonesterified; D008063:Thioctic Acid; D008715:Methionine; D002794:Choline