Hepatic glutathione biosynthetic capacity in hyperthyroid rats.
The influence of hyperthyroidism on the capacity of the liver to synthesize glutathione (GSH) was evaluated as a possible mechanism of depletion of the tripeptide. For this purpose, the effect of daily doses of 0.1 mg 3, 3',5-tri-iodothyronine (T3)/kg for 3 consecutive days on hepatic GSH biosynthetic capacity was assessed by a combined assay measuring gamma-glutamylcysteinyl synthase and GSH synthase simultaneously. T3 treatment induced a significant 56% depletion of liver GSH in parallel with an increase in the rate of GSH synthesis, the latter effect being completely abolished by L-buthionine sulfoximine. According to these data, the fractional rate of hepatic GSH turnover exhibited a 3.2-fold enhancement in hyperthyroid rats compared to control animals. It is concluded that the enhanced GSH utilization in the liver of hyperthyroid rats previously observed [Fernández et al., Endocrinology 129, 85-91, 1991], is accompanied by an increment in GSH synthesis that is insufficient to sustain the basal levels of the tripeptide observed in euthyroid animals, thus establishing a low steady-state content of GSH in the tissue.
Fernández
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Departamento de Bioquímica, Facultad de Medicina, Universidad de Chile, Santiago-7, Chile.
Videla
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LA
D000818:Animals; D001831:Body Temperature / Q000187:drug effects; D005260:Female; D005721:Glutamate-Cysteine Ligase / Q000378:metabolism; D005978:Glutathione / Q000096:biosynthesis*; D005982:Glutathione Transferase / Q000378:metabolism; D006980:Hyperthyroidism / Q000139:chemically induced / Q000503:physiopathology; D008099:Liver / Q000378:metabolism*; D018384:Oxidative Stress / Q000187:drug effects; D051381:Rats; D017207:Rats, Sprague-Dawley; D014284:Triiodothyronine / Q000008:administration & dosage / Q000097:blood
D014284:Triiodothyronine; D005982:Glutathione Transferase; D005721:Glutamate-Cysteine Ligase; D005978:Glutathione