X-Message-Number: 17139
Date: Sun, 29 Jul 2001 05:18:23 -0700 (PDT)
From: Doug Skrecky <>
Subject: could ursodeoxycholate reduce vitrification solution toxicity?

<1> of <2>
Title
  Ursodeoxycholate protects against ethanol-induced liver
  mitochondrial injury.
Source
  Life Sciences.  63(25):2259-70, 1998.
Abstract
  The purpose of this work was to examine whether ursodeoxycholate (UDC), a
  hydrophilic bile salt, could reduce mitochondrial liver injury from chronic
  ethanol consumption in rats. Animals were pair-fed liquid
  diets containing 36% of calories as ethanol or isocaloric
  carbohydrates. They were randomly assigned into 4 groups of 7 rats each and
  received a specific treatment for 5 weeks: control diet,
  ethanol diet, control diet + UDC, and
  ethanol diet + UDC. Respiratory rates of isolated liver
  mitochondria were measured using a Clark oxygen electrode with sodium
  succinate as substrate. Mitochondria from rats chronically fed
  ethanol demonstrated an impaired ability to produce energy.
  At the fatty liver stage, the ADP-stimulated respiration (V3) was depressed
  by 33%, the respiratory control ratio (RC) by 25% and the P/O ratio by 15%.
  In ethanol-fed rats supplemented with UDC, both the rate and
  efficiency of ATP synthesis via the oxidative phosphorylation were improved:
  V3 was increased by 35%, P/O by 8%. All the respiratory parameters were
  similar in control group and control + UDC group. On the other hand, the
  number and size of mitochondria were assessed by electron microscopy and
  computer-assisted quantitative analysis. The number of mitochondria from
  ethanol-treated rats was decreased by 29%, and they were
  enlarged by 74%. Both parameters were normalized to control values by UDC
  treatment. These studies demonstrate that UDC has a protective effect against
  ethanol-induced mitochondrial injury by improving ATP
  synthesis and preserving liver mitochondrial morphology. These UDC positive
  effects may contribute to the observed decrease in fat accumulation and may
  delay the progression of alcoholic injury to more advanced stages.

<2>
Title
  Effect of ursodeoxycholic acid on in vivo
  and in vitro toxic liver injury in rats.
Source
  Alimentary Pharmacology & Therapeutics.  8(3):315-22, 1994 Jun.
Abstract
  BACKGROUND: Benefits of ursodeoxycholic
  acid (UDCA) in cholestatic disorders have been well
  documented. However, the therapeutic potential of UDCA in parenchymal liver
  disease is unclear. METHODS: We tested UDCA in rat models of hepatotoxicity:
  (a) in subacute liver injury induced by repetitive CCl4 and dietary ethyl
  alcohol (ETH) over seven weeks while receiving oral UDCA; and, (b) in liver
  slides incubated with CCl4, ETH or p-acetaminophen (APAP) when UDCA was added
  to the incubating solution. RESULTS: Experiment 1: CCl4 combined with ETH
  reduced the body weights and resulted in 43% mortality. There was a
  significant rise in serum ALT, alkaline phosphatase, lipoperoxides (LPO) and
  in hepatic weight, triglycerides, LPO and histological scores of liver
  injury. Experiment 2: When liver slides were incubated with hepatotoxins
  there was an increased transfer of AST and LPO from the tissue into the
  incubate and a reduction in the valine and thymidine incorporation into the
  liver proteins or DNA. In none of these situations, whether the liver damage
  was severe or mild, in vivo or in vitro, UDCA did abolish these hepatotoxic
  effects. CONCLUSION: In contrast to clinical cholestatic disorders where the
  reported benefits of UDCA depend on replacement of the accumulated
  hydrophobic bile acids, these bile acids
  have a less prominent role in toxic liver injury and UDCA is ineffective.

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