Melatonin but not vitamins C and E maintains glutathione homeostasis in t-butyl hydroperoxide-induced mitochondrial oxidative stress.

Abstract

SPECIFIC AIMTo assess whether the antioxidant properties of melatonin are suitable to maintain GSH homeostasis counteracting mitochondrial oxidative stress.PRINCIPAL FINDINGS1. Effect of melatonin, NAC, ascorbate, and Trolox on mitochondrial GSH and GSSG levelsIn basal conditions, i.e., mitochondria incubated in the absence of t-BHP, melatonin (100 nM) significantly (P<0.001) increased the content of GSH and decreased that of GSSG in brain (GSH: 6.82±0.78 to 10.13±0.42 nmol/mg prot) and liver (GSH: 11.54±0.89 to 19.43±0.80 nmol/mg prot; GSSG: 1.44±0.22 to 0.06±0.007 nmol/mg prot) mitochondria. The other antioxidants tested were unable to exert a similar effect of melatonin, and only the dose of 1000 μM Trolox increased GSH levels (11.50 ± 0.43 nmol/mg prot) in brain mitochondria.After incubation with 100 μM t-BHP, practically all GSH was oxidized to GSSG (Fig. 1)⤻ . Melatonin (100 nM) counteracted these toxic effects, recovering the basal levels of GSH and GSSG. In this situation, i.e., t-BHP-induced oxid...