Beneficial effects of silibinin against the progression of metabolic syndrome, increased oxidative stress, and liver steatosis in Psammomys obesus, a relevant animal model of human obesity and diabetes

被引:41
作者
Bouderba, Saida [1 ]
Sanchez-Martin, Carlos [2 ]
Villanueva, Gloria R. [2 ]
Detaille, Dominique [3 ,4 ]
Koceir, E. Ahmed [1 ]
机构
[1] Univ Sci & Technol Houari Boumediene USTHB, Dept Biol Sci & Physiol, Lab Bioenerget & Intermediary Metab, Algiers, Algeria
[2] Univ Salamanca, Fac Pharm, Dept Physiol & Pharmacol, E-37008 Salamanca, Spain
[3] Univ Bordeaux, Rhythmol & Heart Modeling Inst LIRYC, Bordeaux, France
[4] INSERM, U1045, Cardiothorac Res Ctr CRCTB, F-33604 Pessac, France
关键词
antioxidant systems; dyslipidemia; hepatic insulin resistance; Psammomys obesus; silibinin; Type; 2; diabetes; PERIFUSED RAT HEPATOCYTES; INSULIN-RESISTANCE; FATTY LIVER; SUPEROXIDE-DISMUTASE; SILYBUM-MARIANUM; SILYMARIN; HYPERGLYCEMIA; DISEASE; HYPERINSULINEMIA; EXCRETION;
D O I
10.1111/1753-0407.12083
中图分类号
R5 [内科学];
学科分类号
1002 ; 100201 ;
摘要
BackgroundInsulin resistance and oxidative stress are major pathogenic mechanisms leading to chronic liver diseases in diabetic subjects. The gerbil Psammomys obesus is a unique model of nutritional diabetes resembling the disease in humans. This study investigated whether the natural ingredient silibinin, known as hepatoprotective, could decrease oxidative stress and reduce liver damage in obese gerbils. MethodsControl animals were fed their vegetable-based low caloric diet while two other rat groups ingested a high calorie diet for 14 weeks. Silibinin, or its vehicle, was administrated by gastric intubation (100mg/kg per day) from the 7th week of treatment, which corresponds to an established insulin resistance state. At the end of the experiments, the hepatic biochemical profile, markers of oxidative stress in either plasma or liver tissue, and histological alterations were examined. ResultsDiabetic P.obesus displayed many metabolic disturbances (hyperinsulinemia, hyperglycemia, dyslipidemia), which were aggravated for the last 8 weeks. These events were coupled with greater oxidative stress (decline in glutathione, rise in lipoperoxidation). In addition, glutathione peroxidase activity was reduced while the level of superoxide dismutase was elevated. Interestingly, treatment with silibinin alleviated most of the metabolic defects, especially high triglyceride levels, reduced insulin resistance and largely restored antioxidant status. Also, Masson's trichrome staining revealed distinct steatosis, yet silibinin partially reversed this manifestation. ConclusionSilibinin affords substantial protection against the progression of insulin resistance in Type 2 diabetes mellitus for P.obesus by hampering the oxidative process and improving hepatic metabolism.
引用
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页码:184 / 192
页数:9
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