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Effect of silibinin on endothelial dysfunction and ADMA levels in obese diabetic mice.
- Source :
-
Cardiovascular diabetology [Cardiovasc Diabetol] 2011 Jul 14; Vol. 10, pp. 62. Date of Electronic Publication: 2011 Jul 14. - Publication Year :
- 2011
-
Abstract
- Background: Cardiovascular diseases (CVD) in diabetic patients have endothelial dysfunction as a key pathogenetic event. Asymmetric dimethylarginine (ADMA), an endogenous inhibitor of nitric oxide synthase (NOS), plays a pivotal role in endothelial dysfunction. Different natural polyphenols have been shown to preserve endothelial function and prevent CVD. In this study, we assessed the effect of silibinin, a widely used flavonolignan from milk thistle, on ADMA levels and endothelial dysfunction in db/db mice.<br />Methods: Eight-week-old db/db mice were administrated a 20 mg/Kg i.p. daily dose of silibinin (n = 6) or vehicle (n = 6) for four weeks. Heterozygous lean db/m mice served as control. Plasma, aorta and liver ADMA levels were determined by ELISA. Vascular reactivity to phenilephrine (PE), acetylcholine (ACh), sodium nitroprusside (SNP) and ADMA was assessed in isolated aortic segments, in wire myograph.<br />Results: Plasma and aorta ADMA levels were higher in db/db than in control lean mice. Silibinin administration markedly decreased plasma ADMA; consistently, aorta ADMA was reduced in silibinin-treated animals. Plasma and aorta ADMA levels exhibited a positive correlation, whereas liver ADMA was inversely correlated with both plasma and aorta ADMA concentrations. Endothelium-(NO)-dependent vasodilatation to ACh was impaired in db/db mice and was restored in the silibinin group, in accordance with the observed reduction of plasma and vascular levels of ADMA. Endothelium-independent vasodilatation to SNP was not modified by silibinin administration; contractile tone induced in isolated aorta from db/db mice by challenging with exogenous ADMA was not affected by the treatment.<br />Conclusions: Silibinin markedly improves endothelial dysfunction in db/db mice by reducing circulating and vascular ADMA levels. Clinical studies are warranted to assess the efficacy of silibinin for cardiovascular protection.
- Subjects :
- Acetylcholine pharmacology
Animals
Antioxidants pharmacology
Aorta drug effects
Aorta metabolism
Aorta physiopathology
Arginine metabolism
Disease Models, Animal
Endothelium, Vascular metabolism
Insulin Resistance physiology
Liver metabolism
Male
Mice
Mice, Obese
Nitroprusside pharmacology
Phenylephrine pharmacology
Silybin
Vasoconstrictor Agents pharmacology
Vasodilator Agents pharmacology
Arginine analogs & derivatives
Diabetes Mellitus metabolism
Diabetes Mellitus physiopathology
Endothelium, Vascular drug effects
Endothelium, Vascular physiopathology
Obesity metabolism
Obesity physiopathology
Silymarin pharmacology
Subjects
Details
- Language :
- English
- ISSN :
- 1475-2840
- Volume :
- 10
- Database :
- MEDLINE
- Journal :
- Cardiovascular diabetology
- Publication Type :
- Academic Journal
- Accession number :
- 21756303
- Full Text :
- https://doi.org/10.1186/1475-2840-10-62