The Effects of Allopurinol in Hepatic Ischemia and Reperfusion: Experimental Study in Rats

Abstract

Background/Aims: Some studies have shown that postischemic hepatic dysfunction is mainly due to oxygen free radicals that are generated by xanthine oxidase. The present study was undertaken to determine the effect of allopurinol, an inhibitor of xanthine oxidase, on oxidative stress, liver injury and histologic alterations induced by hepatic ischemia-reperfusion in rats. Methods: One hundred and sixty Wistar rats were used and divided into three groups. Group 1: sham operation; group 2: 50 min of ischemia followed by 1 h of reperfusion, and group 3: pretreatment with allopurinol and 50 min of ischemia followed by 1 h of reperfusion. The effect of allopurinol was evaluated by plasma levels of alanine aminotransferase and aspartate aminotransferase, histopathologic studies, and lipid peroxidation measured by the thiobarbituric acid reactive substances method and chemiluminescence initiated by tert-butyl hydroperoxide technique. Results: Ischemia followed by reperfusion promoted an increase in lipid peroxidation of the hepatic cells when compared to the sham-operated group (p < 0.05). This increase was attenuated in the group treated with allopurinol (p < 0.05). Allopurinol also showed a protective effect on hepatocellular necrosis (p < 0.05), and the plasma levels of liver enzymes returned earlier to the normal range in rats pretreated with allopurinol in comparison to those that did not receive the drug (p < 0.05). Conclusions: Allopurinol exerted a protective effect on hepatic ischemia and reperfusion in rats. The administration of this drug prior to liver operations should be considered to be submitted to trials in humans.

An in vivo ESR spin-trapping study: Free radical generation in rats from formate intoxication— role of the Fenton reaction

“…Allopurinol was administered to rats i.p. (50 mg͞kg), 24 and 5 h before the injection of sodium formate and POBN (16). AT was given to rats (1 g͞kg, i.p.)…”

Allopurinol and xanthine oxidase inhibition in liver ischemia reperfusion

“…There are a few studies that have shown allopurinol has no effect on transaminases [5,44] and that LDH [42,45] increases. In most cases, if the attenuation in transaminase increases was not seen immediately, it occurred at least 5 h after reperfusion had elapsed [10,37,41,42]. However when the period was extended to 24 h, no effect was observed by Metzger et al [5].…”

“…Rhoden et al [41] 2001 Rat Liver IR ALLO pretreatment protects against mitochondrial injury, which prevents mitochondrial oxidant stress and lipid peroxidation and preservation of hepatic energy metabolism.…”

“…Positive effect a 48 h and 24 h before reperfusion Nauta et al [13] 24 h and 1 h before operation Liu et al [8] 18 h and 1 h before ischemia Lee and Lee [7] 18 h and 1 h before ischemia Jeon et al [10] b 5 h and 1 h before reperfusion Rhoden et al [41] c 4 h and 10 min before ischemia Castillo et al [40] 4 h before ischemia Castillo et al [40] 15 min before ischemia Yildirim et al [42] d 10 min before ischemia Taha et al [9] Neutral effect e 10 min before ischemia and at reperfusion Castillo et al [40] At reperfusion Castillo et al [40] Detrimental effect at 3 h after reperfusion f 4 h before laparotomy Lu et al [45] a Positive effect was determined as a significant decrease in transaminases of animals pretreated with allopurinol compared to control animals b Positive effect at 5 h and neutral effect at 0 or 1 h after reperfusion c Positive effect at 48 h and neutral effect at 0, 24, or 72 h after reperfusion d Positive effect at 15 and 45 min after reperfusion and neutral effect at 45 min of ischemia e Neutral effect was determined as no significant difference in transaminases between animals pretreated with allopurinol and controls f Detrimental effect was determined as a significant increase in transaminases of animals pretreated with allopurinol compared to control animals, measured at 3 h after reperfusion…”

Effects of the Free Radical Scavenger Dimethyl Sulphoxide on Experimental Normothermic Ischaemia of the Liver

“…Studies on hepatic I/R models have shown greater free radical generation with continuous clamping techniques [30]followed by rapid exhaustion of naturally occurring endogenous anti-oxidants during the reperfusion periods. Here, a range of administered free radical scavengers and inhibitors have been shown experimentally to attenuate free radical generation including superoxide dismutase, allopurinol, N-acetylcysteine and α-tocopherol [31, 32, 33]. DMSO was utilized in this study partly because of its Na + -K + - ATPase inhibiting properties, since it was hoped that this would affect the reduction reported in intracellular ATP frequently observed during experimental ischaemia [34].…”