Chronic administration of ursodeoxycholic acid decreases portal pressure in rats with biliary cirrhosis

Abstract

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.

Inhibition of nitric oxide synthesis during induced cholestasis ameliorates hepatocellular injury by facilitating S-nitrosothiol homeostasis

“…It has been recently shown that chronic oral administration of UDCA decreases portal pressure, NO production and iNOS expression in BDL cirrhotic rats. 39 In our model, the administration of TUDCA reduced NO production to some extent, although no effect was observed on Nos2 mRNA levels. Conceivably, the full effect of TUDCA on NO production and iNOS expression may only be observed when cirrhosis develops.…”

Bile acids and cardiovascular function in cirrhosis

“…Thus, Schiedermaier et al . reported a decrease in diastolic blood pressure but not portal flow in a small human cross‐over study, while Yang et al . described a reduction in portal pressure due to diminished intrahepatic resistance in a rat model.…”

Mechanisms of the prevention and inhibition of the progression and development of non‐alcoholic steatohepatitis by genetic and pharmacological decoy receptor 3 supplementation

“…Murine liver sample sections were formalin‐fixed, paraffin‐embedded, and stained with hematoxylin–eosin, IFNγ, SOD, and Sirius Red. The samples embedded in optimal cutting temperature (OCT) compound were stained with Oil red O; NAFLD activity scores (NAS) were applied to evaluate hepatic steatosis and NASH . In addition, OCT‐embedded cryostat liver sections were used to investigate the hepatic infiltration of leukocytes and M1 KCs, which were stained by single fluorescein‐isothiocyanate (FITC)‐conjugated CD68 antibody and first FITC‐conjugated F4/80 antibody followed by second phycoerythrin‐conjugated CD11c antibody, respectively.…”

“…The samples embedded in optimal cutting temperature (OCT) compound were stained with Oil red O; NAFLD activity scores (NAS) were applied to evaluate hepatic steatosis and NASH. 25 In addition, OCTembedded cryostat liver sections were used to investigate the hepatic infiltration of leukocytes and M1 KCs, which were stained by single fluorescein-isothiocyanate (FITC)conjugated CD68 antibody and first FITC-conjugated F4/80 antibody followed by second phycoerythrinconjugated CD11c antibody, respectively. After counterstained with Fluoromount-G medium (SouthernBiotech, Birmingham, AL, USA), each slide was evaluated for the numbers of CD68 + cells per 1 mm 2 in the single FITC images.…”