Mitochondrial glutathione content determines the rate of liver regeneration after partial hepatectomy in eu- and hypothyroid rats.

BACKGROUND/AIMS: Mitochondrial glutathione has been postulated to affect mitochondrial function and liver regeneration.

METHODS

Mitochondrial respiration, total and oxidized glutathione, and liver regeneration were assessed after partial hepatectomy in glutathione-depleted and in hypothyroid rats with/without supplementation of glutathione ester.

RESULTS

Mitochondrial, cytosolic and circulating glutathione levels were lower in glutathione-depleted rats. Hepatectomy was followed by significant changes of intra- and extracellular glutathione and of mitochondrial respiration. In glutathione-deficient rats, the recovery of mitochondrial function and the liver regeneration were delayed. Administration of glutathione ester partially corrected the fall of cytosolic and mitochondrial glutathione following hepatectomy, reduced mitochondrial oxidative damage, and accelerated the restoration of mitochondrial respiration and the rate of liver regeneration. In hypothyroid rats, intracellular glutathione homeostasis and mitochondrial respiration were impaired already at baseline; slower regeneration and mitochondrial oxidative alterations were observed after hepatectomy. Glutathione ester ameliorated the regenerative response in hypothyroid rats by providing higher concentrations of cytosolic and mitochondrial glutathione.

CONCLUSIONS

Glutathione depletion and hypothyroidism affect the mitochondrial function during liver regeneration. Liver regenerates more slowly in glutathione-depleted and in hypothyroid rats. The earlier restoration of mitochondrial function and the higher rate of proliferation in glutathione ester treated rats suggest that the maintenance of intracellular glutathione facilitates liver regeneration.