Respective roles of free radicals and energy supply in hypoxic rat liver injury after reoxygenation.
Livers from fasted rats subjected to 60 min of hypoxia followed by 25 min of reflow exhibited a significant release of lactate dehydrogenase (LDH) and protein into the perfusate together with high rates of oxygen consumption, depletion of hepatic glutathione (GSH) and accumulation of thiobarbituric acid reactants (TBAR) in the liver. These changes were observed in the presence and absence of added xanthine (25 microM) and were significantly diminished when experiments were carried out in the presence of either 1 mM allopurinol or 100 microM Trolox. Allopurinol inhibited by 79% the production of uric acid by the liver, which was not altered by Trolox. Hypoxia-reflow studies performed in the presence of 25 microM 2,4-dinitrophenol (DNP) showed a drastic enhancement in LDH (244%) and protein (104%) efflux from the liver, compared with the effects found in its absence, with a moderate increase (35%) in tissue TBAR levels. Liver perfusion in the presence of both allopurinol and DNP exhibited a normalization of the tissue content of GSH and TBAR, while the net increase in LDH and protein release elicited by DNP alone was inhibited by only 20 and 25%, respectively. Similar results were obtained in experiments in which allopurinol was replaced by Trolox. These studies indicate that production of oxygen free-radicals are involved in hypoxic liver injury upon reflow, but its relative importance is significantly diminished when energy stores are severely diminished.
Videla
L A
LA
Departamento de Ciencias Biológicas, Facultad de Medicina, Universidad de Chile, Santiago.
D019297:2,4-Dinitrophenol; D000493:Allopurinol / Q000494:pharmacology; D000818:Animals; D004140:Dinitrophenols / Q000494:pharmacology; D004734:Energy Metabolism; D005609:Free Radicals; D005978:Glutathione / Q000378:metabolism; D000860:Hypoxia / Q000378:metabolism*; D066298:In Vitro Techniques; D008099:Liver / Q000187:drug effects / Q000293:injuries / Q000378:metabolism*; D008297:Male; D010100:Oxygen / Q000378:metabolism; D010477:Perfusion; D051381:Rats; D011919:Rats, Inbred Strains
D004140:Dinitrophenols; D005609:Free Radicals; D000493:Allopurinol; D005978:Glutathione; D019297:2,4-Dinitrophenol; D010100:Oxygen