Chronic administration of ursodeoxycholic acid decreases portal pressure in rats with biliary cirrhosis.
Liver cirrhosis is characterized by increased IHR (intrahepatic resistance) and lipid peroxidation, and decreased antioxidative defence. The present study investigates the effects of administration for 1 month of the antioxidant UDCA (ursodeoxycholic acid) in BDL (bile-duct-ligated) cirrhotic rats. Splanchnic haemodynamics, IHR, hepatic levels of TBARS (thiobarbituric acid-reacting substances), GSH (glutathione), SOD (superoxide dismutase) activity, nitrite, PIIINP (N-terminal propeptide of type III procollagen) and collagen deposition, histological examination of liver, mRNA expression of PIIIP-alpha1 (type III procollagen) and TGF-beta1 (transforming growth factor-beta1), protein expression of TXS (thromboxane synthase) and iNOS (inducible NO synthase), and TXA2 (thromboxane A2) production in liver perfusates were measured. The results showed that portal pressure and IHR, hepatic levels of PIIINP, hepatic collagen deposition, mRNA expression of PIIIP-alpha1 and TGF-beta1, protein expression of iNOS and TXS, and production of TXA2 in liver perfusates were significantly decreased in UDCA-treated BDL rats. The increased levels of hepatic GSH and SOD activity and decreased levels of TBARS and nitrite were also observed in UDCA-treated BDL rats. In UDCA-treated BDL rats, the reduction in portal pressure resulted from a decrease in IHR, which mostly acted through the suppression of hepatic TXA2 production and lipid peroxidation, and an increase in antioxidative defence, leading to the prevention of hepatic fibrosis.
Yang
Ying-Ying
YY
Division of General Medicine, Department of Medicine, Taipei Veterans General Hospital, Taipei 11217, Taiwan.
Huang
Yi-Tsau
YT
Lee
Kuei-Chuan
KC
Lee
Fa-Yauh
FY
Lee
Tzung-Yan
TY
Hou
Ming-Chih
MC
Lin
Han-Chieh
HC
Lee
Shou-Dong
SD
D000818:Animals; D000975:Antioxidants / Q000008:administration & dosage / Q000378:metabolism / Q000627:therapeutic use*; D024061:Collagen Type III / Q000096:biosynthesis / Q000235:genetics; D004334:Drug Administration Schedule; D004353:Drug Evaluation, Preclinical; D005786:Gene Expression Regulation / Q000187:drug effects; D006439:Hemodynamics / Q000187:drug effects; D006975:Hypertension, Portal / Q000188:drug therapy* / Q000209:etiology / Q000503:physiopathology; D015227:Lipid Peroxidation / Q000187:drug effects; D008099:Liver / Q000378:metabolism / Q000503:physiopathology; D008102:Liver Circulation / Q000187:drug effects; D008105:Liver Cirrhosis, Biliary / Q000150:complications / Q000188:drug therapy* / Q000473:pathology / Q000503:physiopathology; D008297:Male; D010446:Peptide Fragments / Q000096:biosynthesis / Q000235:genetics; D017082:Portal Pressure / Q000187:drug effects; D011347:Procollagen / Q000096:biosynthesis / Q000235:genetics; D012333:RNA, Messenger / Q000235:genetics; D051381:Rats; D017207:Rats, Sprague-Dawley; D014580:Ursodeoxycholic Acid / Q000008:administration & dosage / Q000627:therapeutic use*; D014655:Vascular Resistance / Q000187:drug effects
D000975:Antioxidants; D024061:Collagen Type III; D010446:Peptide Fragments; D011347:Procollagen; D012333:RNA, Messenger; C041876:procollagen Type III-N-terminal peptide; D014580:Ursodeoxycholic Acid