No documentable role for xanthine oxidase in the pathogenesis of hepatic in vivo ischaemia/reperfusion injury.
An investigation was made into the possible involvement of the enzyme xanthine oxidase (XO) (EC 1.1.3.22), both reversible (XOrev) and irreversible (XOirr), in damage observed after short-term in vivo hepatic ischaemia/reperfusion (60 or 120 min I and 15 min R) in fasted rats with: (i) a physiological content of XO (25%); and (ii) higher XO percentage (45%). In the latter the hepatic XO physiological percentage was increased by diethylmaleate treatment (300 mg kg-1) that depleted the cytosolic glutathione (GSH) to 14% of the controls. It was shown that, in animals with physiological content of XO, 60 and 120 min of hepatic ischaemia followed by 15 min reperfusion results in decreased GSH levels, and significantly increased alanine aminotransferase (ALT) and aspartate aminotransferase (AST) serum levels, without any modification of either the percentages of XO (XOirr and XOrev) or the hepatic thiobarbituric acid reactive substances (TBARS). Sixty minutes of ischaemia/reperfusion in rats with the higher XO level and lower hepatic GSH content led to further conversion of XDH to XOrev, with no increase in XOirr. In addition, the ALT and AST serum levels in these animals rose to the same extent as in normal rats after 120 min ischaemia and 15 min reperfusion, this extent being observed to be associated with a moderate increase in thiobarbituric acid reactive substances (TBARS). However, the administration of allopurinol, at a dose of 50 mg kg-1, which almost completely inhibits XO activity, did not lead to any decrease in liver damage or TBARS.(ABSTRACT TRUNCATED AT 250 WORDS)
Cighetti
G
G
Department of Medical Chemistry and Biochemistry, University of Milan, Italy.
Debiasi
S
S
Paroni
R
R
D000410:Alanine Transaminase / Q000097:blood; D000493:Allopurinol / Q000494:pharmacology; D000818:Animals; D001219:Aspartate Aminotransferases / Q000097:blood; D005978:Glutathione / Q000378:metabolism; D007511:Ischemia / Q000201:enzymology*; D008099:Liver / Q000098:blood supply* / Q000473:pathology; D008297:Male; D008298:Maleates; D051381:Rats; D015427:Reperfusion Injury / Q000201:enzymology*; D014969:Xanthine Oxidase / Q000037:antagonists & inhibitors / Q000378:metabolism*
D008298:Maleates; D000493:Allopurinol; D014969:Xanthine Oxidase; D001219:Aspartate Aminotransferases; D000410:Alanine Transaminase; C014476:diethyl maleate; D005978:Glutathione