Liver damage during ischemia/reperfusion and glutathione: implications for potential organ donors.
Free radicals play a central role in the development of liver ischemia/reperfusion (I/R) injury. Reduced glutathione (GSH) is the main hepatic free radical scavenger. Brain-dead patients exhibit abnormalities of endocrine status. Many clinicians administer thyroid hormones to improve the transplantation outcomes. We previously reported that thyroxine (T(4)) pretreatment decreased rat liver tissue GSH, which was associated with increased liver I/R-induced damage. In this study, we investigated whether the reduction in GSH by T(4) pretreatment affected cell viability during anoxia or oxidative stress in suspensions of isolated hepatocytes. Furthermore, we evaluated the levels of GSH in isolated livers from hypothyroid rats preserved at 0-1 degrees C and reperfused. Thyroid hormone modulation was obtained by T(4) or 6-propylthiouracil (PTU) treatment. Isolated hepatocytes from T(4)-pretreated rats that underwent anoxia and oxidative stress, which was induced by tert-butylhydroperoxide, displayed progressive, time-dependent loss of cell viability, which was greater than that in hepatocytes in non-T(4)-pretreated rats. A significant decrease in GSH levels was observed in isolated hepatocytes obtained from hyperthyroid rats compared with those from euthyroid rats. In contrast, administration of the antithyroid drug PTU increased liver concentrations of GSH at the end of reperfusion thereby improving liver function after cold storage. These results may yield new protective strategies in the management of brain-dead organ donors.
Vairetti
M
M
Department of Internal Medicine and Therapeutics, IRCCS Policlinico San Matteo, University of Pavia, Pavia, Italy. vairetti@botta.unipv.it
Ferrigno
A
A
Rizzo
V
V
Richelmi
P
P
Cillo
U
U
Imberti
R
R
D000818:Animals; D015415:Biomarkers / Q000032:analysis; D005978:Glutathione / Q000378:metabolism*; D022781:Hepatocytes / Q000473:pathology; D007037:Hypothyroidism; D007770:L-Lactate Dehydrogenase / Q000032:analysis; D008099:Liver / Q000473:pathology* / Q000503:physiopathology; D008102:Liver Circulation; D018579:Patient Selection; D051381:Rats; D015427:Reperfusion Injury / Q000150:complications*; D014019:Tissue Donors
D015415:Biomarkers; D007770:L-Lactate Dehydrogenase; D005978:Glutathione