Effect of thyroid hormone administration on the depletion of circulating glutathione in the isolated perfused rat liver and its relationship to basolateral gamma-glutamyltransferase activity.
The influence of thyroid hormone administration on liver glutathione (GSH) extraction in the isolated perfused liver was studied in fed rats for a period of 1-7 days following a single dose of 0.1 mg 3,5,3'-triiodothyronine (T3)/kg. T3 treatment led to an early and transient calorigenic response, as well as an enhancement in liver GSH removal, reaching a maximal effect at 2 days after hormone administration, which was normalized in the 3- to 7-day period studied. Addition of the gamma-glutamyltransferase (gamma-GT) inhibitor DL-serineborate (4 mM) to the perfusate abolished the increase in the hepatic removal of GSH elicited by T3, and enhanced the sinusoidal concentration of GSH, studied at 2 days after hormone administration. These data support the role of hepatic basolateral gamma-GT ectoactivity in the depletion of portally added and liver-derived GSH as an adaptive response to recover GSH levels after reduction by T3-induced oxidative stress.
Videla
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LA
Departamento de Bioquimica, Facultad de Medicina, Universidad de Chile, Santiago.
Fernández
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D000818:Animals; D001881:Borates / Q000494:pharmacology; D002462:Cell Membrane / Q000378:metabolism; D005260:Female; D005978:Glutathione / Q000097:blood / Q000378:metabolism*; D066298:In Vitro Techniques; D007700:Kinetics; D008099:Liver / Q000187:drug effects / Q000378:metabolism*; D008954:Models, Biological; D010477:Perfusion; D051381:Rats; D017207:Rats, Sprague-Dawley; D012694:Serine / Q000494:pharmacology; D013997:Time Factors; D014284:Triiodothyronine / Q000494:pharmacology*; D005723:gamma-Glutamyltransferase / Q000037:antagonists & inhibitors / Q000378:metabolism*
D001881:Borates; C040900:serine-borate complex; D014284:Triiodothyronine; D012694:Serine; D005723:gamma-Glutamyltransferase; D005978:Glutathione