Melatonin-induced increased activity of the respiratory chain complexes I and IV can prevent mitochondrial damage induced by ruthenium red in vivo

Melatonin displays antioxidant and free radical scavenger properties. Due t o its ability with which it enters cells, these protective effects are mani fested in all subcellular compartments. Recent studies suggest a role for m elatonin in mitochondrial metabolism. To study the effects of melatonin on this organelle we used ruthenium red to induce mitochondrial damage and oxi dative stress. The results show that melatonin (10 mg/kg i.p.) can increase the activity of the mitochondrial respiratory complexes I and IV after its administration in vivo in a time-dependent manner; these changes correlate well with the half-life of the indole in plasma. Melatonin administration also prevented the decrease in the activity of complexes I and IV due to ru thenium red (60 mu g/kg i.p.) administration. At this dose, ruthenium red d id not induce lipid peroxidation but it significantly reduced the activity of the antioxidative enzyme glutathione peroxidase, an effect also countera cted by melatonin. These results suggest that melatonin modulates mitochond rial respiratory activity, an effect that may account for some of the prote ctive properties of the indoleamine. The mitochondria-modulating role of me latonin may be of physiological significance since it seems that the indole amine is concentrated into normal mitochondria. The data also support a pha rmacological use of melatonin in drug-induced mitochondrial damage in vivo.