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Misoprostol hepatoprotection against ischemia-reperfusion-induced liver injury in the rat

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Abstract

The hepatoprotective effects of misoprostol, a PGE1 analog, against ischemiareperfusion liver injury were studied using a rat partial liver ischemia model. Serum ornithine carbamoyltransferase (OCT) and alanine aminotransferase (ALT) levels were determined as biochemical indices of injury. Hepatic cell necrosis was assessed histologically using tetranitroblue tetrazolium (TNBT) and hematoxylin and eosin (H&E) staining. With placebo treatment, 90 min of partial hepatic ischemia followed by 24 hr of reperfusion resulted in increased levels of serum OCT (760±521IU/liter) and ALT (4327 ±1982 IU/liter), while extensive hepatic necrosis was evident by TNBT and H&E staining. Treatment with two doses of 25 μg misoprostol/kg body weight at 1 min before ischemia and 1 min before reperfusion significantly reduced the serum levels of OCT and ALT (207±189 IU/liter, P<0.01 and 2075±1217 IU/liter, P<0.01, respectively) and hepatic necrosis. When a single dose of misoprostol was administered 1 min before reperfusion, similar protective effects were observed. However, when the treatment of misoprostol was delayed to 1 min after reperfusion, significantly less hepatoprotection was seen. Misoprostol exerted no hepatoprotection at all when it was administered at 5 min or later after reperfusion. These results demonstrate that misoprostol partially protects the liver against ischemia-reperfusion injury in the rat. The observation that the protective effect of misoprostol occurs only within the first minute of reperfusion suggests that its mechanism of action involves an early event in reperfusion injury, such as modifying the effects of reactive oxygen metabolites.

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Authors and Affiliations

  1. Department of Surgery, Monash Medical School, Alfred Hospital, 3181, Prahran, Victoria, Australia

    Sook Ping Lim BSc (Hons), Fiona J. Andrews PhD, Chris Christophi FRACS &  Paul E. O'Brien MD

Authors
  1. Sook Ping Lim BSc (Hons)
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  2. Fiona J. Andrews PhD
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  3. Chris Christophi FRACS
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  4. Paul E. O'Brien MD
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This study is supported by the Australian National Health and Medical Research Council Grant 91/0662.

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Lim, S.P., Andrews, F.J., Christophi, C. et al. Misoprostol hepatoprotection against ischemia-reperfusion-induced liver injury in the rat. Digest Dis Sci 37, 1275–1281 (1992). https://doi.org/10.1007/BF01296572

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  • DOI: https://doi.org/10.1007/BF01296572

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