Inflammation and platelet-activating factor production during hepatic ischemia/reperfusion.
The role of platelet-activating factor as a potential mediator of hepatic inflammatory injury associated with liver ischemia/reperfusion was investigated using a partial no-flow model in rats in vivo. Platelet-activating factor levels of livers from sham-operated rats and from animals experiencing hepatic reperfusion for less than 6 hr were very low. They were observed to increase significantly after 12 hr of reperfusion and reached peak levels after a 24-hr reperfusion period, a time when maximal hepatic injury and inflammation occurred. Treatment of experimental rats with WEB2170, a platelet-activating factor receptor antagonist, attenuated the hepatic injury and inflammation, as evidenced by decreases in plasma ALT and in hepatocyte necrosis and neutrophil infiltration. Both inactivation of Kupffer cells with gadolinium chloride and inhibition of the formation of reactive oxygen species with allopurinol reduced platelet-activating factor production in the liver, whereas induction of neutropenia had no effect, suggesting that interaction of Kupffer cells with oxygen-derived free radicals may be a plausible mechanism for hepatic platelet-activating factor accumulation. It is concluded that platelet-activating factor contributes to the inflammatory consequences of ischemia/reperfusion underlying late-phase hepatic injury.
Zhou
W
W
Department of Biochemistry, University of Texas Health Science Center, San Antonio 78284-7760.
McCollum
M O
MO
Levine
B A
BA
Olson
M S
MS
D000410:Alanine Transaminase / Q000097:blood; D000493:Allopurinol / Q000494:pharmacology; D000818:Animals; D001381:Azepines / Q000494:pharmacology; D005682:Gadolinium / Q000494:pharmacology; D006505:Hepatitis / Q000209:etiology*; D007511:Ischemia; D007962:Leukocytes / Q000473:pathology; D008099:Liver / Q000098:blood supply* / Q000378:metabolism / Q000473:pathology; D008297:Male; D009336:Necrosis; D010972:Platelet Activating Factor / Q000037:antagonists & inhibitors / Q000096:biosynthesis*; D051381:Rats; D017207:Rats, Sprague-Dawley; D015427:Reperfusion Injury / Q000150:complications* / Q000473:pathology; D014230:Triazoles / Q000494:pharmacology
D001381:Azepines; D010972:Platelet Activating Factor; D014230:Triazoles; D000493:Allopurinol; D005682:Gadolinium; C063964:bepafant; D000410:Alanine Transaminase; C038958:gadolinium chloride