Resveratrol reduces matrix metalloproteinases and alleviates intrahepatic cholestasis of pregnancy in rats

Can J Physiol Pharmacol. 2016 Apr;94(4):402-7. doi: 10.1139/cjpp-2015-0454. Epub 2015 Dec 15.

Abstract

Intrahepatic cholestasis of pregnancy (ICP) is a severe liver disorder occurring specifically in pregnancy, and matrix metalloproteinase (MMP)-2 and MMP-9 were found to be elevated in ICP patients. Using ethinylestradiol-induced ICP rats as the model, we examined the effect of resveratrol on ICP symptoms such as bile flow rate, serum enzymatic activities, and TBA concentration, as well as MMP levels, and compared with the known ICP drug ursodeoxycholic acid. Both MMP-2 and MMP-9 were upregulated in ICP rats, and resveratrol treatment could inhibit the elevation of both MMPs, whereas ursodeoxycholic acid did not exhibit any effect. Although ursodeoxycholic acid alleviated ICP symptoms, resveratrol treatment in general exhibited better outcome in restoring bile flow rate, serum enzymatic activities, and TBA concentration. Our results for the first instance strongly supported the potential of RE as a new therapeutic agent in treating ICP, possibly through inhibiting MMP-2 and MMP-9.

Keywords: acide ursodéoxycholique; acides biliaires totaux; cholestase intrahépatique de la grossesse; intrahepatic cholestasis of pregnancy; matrix metalloproteinase; métalloprotéases de la matrice; resveratrol; resvératrol; total bile acid; ursodeoxycholic acid.

Publication types

  • Research Support, Non-U.S. Gov't

MeSH terms

  • Animals
  • Cholestasis, Intrahepatic / drug therapy*
  • Cholestasis, Intrahepatic / metabolism
  • Female
  • Matrix Metalloproteinase 2 / metabolism*
  • Matrix Metalloproteinase 9 / metabolism*
  • Pregnancy
  • Pregnancy Complications / drug therapy*
  • Pregnancy Complications / metabolism
  • Rats
  • Rats, Sprague-Dawley
  • Resveratrol
  • Stilbenes / pharmacology*
  • Ursodeoxycholic Acid / metabolism

Substances

  • Stilbenes
  • Ursodeoxycholic Acid
  • Matrix Metalloproteinase 2
  • Matrix Metalloproteinase 9
  • Resveratrol

Supplementary concepts

  • Intrahepatic Cholestasis of Pregnancy