Potentiation of ischemia-reperfusion liver injury by hyperthyroidism in the rat.
Parameters related to hepatic oxidative stress, cell injury, and liver histology were determined in control rats and in animals treated with 3,3',5-triiodothyronine (T3), after in vitro perfusion under normoxic or ischemia-reperfusion conditions. Thyroid calorigenesis was found concomitantly with higher rates of hepatic O2 consumption and thiobarbituric acid reactive substances (TBARS) formation, glutathione (GSH) depletion, enhanced TBARS/GSH ratio as indicator of oxidative stress, and higher sinusoidal lactate dehydrogenase (LDH) efflux compared to control values, assessed under normoxic conditions. Perfused livers from control animals subjected to ischemia-reperfusion exhibited significant increases in the TBARS/GSH ratio and in the sinusoidal LDH efflux over values obtained under normoxic conditions, concomitantly with the appearance of small foci of necrotic cells in centrilobular and midzonal areas of the liver lobule. These parameters were further modified in the liver of hyperthyroid rats subjected to ischemia-reperfusion, with elevations in the TBARS/GSH ratio and in the sinusoidal LDH efflux largely exceeding the sum of effects elicited by hyperthyroidism or ischemia-reflow alone. In this situation, liver injury was more pronounced than in control rats, being characterized by multifocal areas of necrotic cells, irregularly distributed in the hepatic lobule, with lymphoid and macrophagic reaction. It is concluded that the concurrence of the hepatic mechanisms related to the oxidative stress underlying thyroid calorigenesis and ischemia-reoxygenation exacerbates liver injury, which seems to be mediated by potentiation of the prooxidant state of the organ.
Troncoso
P
P
Department of Biochemistry, Faculty of Medicine, University of Chile, Santiago, Chile.
Smok
G
G
Videla
L A
LA
D000818:Animals; D001831:Body Temperature; D001835:Body Weight; D005978:Glutathione / Q000378:metabolism; D006651:Histocytochemistry; D006980:Hyperthyroidism / Q000150:complications*; D007770:L-Lactate Dehydrogenase / Q000378:metabolism; D008099:Liver / Q000098:blood supply* / Q000378:metabolism* / Q000473:pathology; D008297:Male; D009929:Organ Size; D018384:Oxidative Stress; D010101:Oxygen Consumption; D051381:Rats; D017207:Rats, Sprague-Dawley; D017382:Reactive Oxygen Species / Q000378:metabolism; D015427:Reperfusion Injury / Q000209:etiology* / Q000378:metabolism; D017392:Thiobarbituric Acid Reactive Substances / Q000032:analysis; D014284:Triiodothyronine / Q000097:blood / Q000494:pharmacology
D017382:Reactive Oxygen Species; D017392:Thiobarbituric Acid Reactive Substances; D014284:Triiodothyronine; D007770:L-Lactate Dehydrogenase; D005978:Glutathione