Table 1.
Melatonin activity in bioenergetic functions: evidence from in vitro and in vivo studies.
| Animal model studies (in vitro and in vivo) | Pretreatment | Posttreatment with melatonin | Reference(s) |
|---|---|---|---|
| Ruthenium red-effect on ETC system | Inhibition of complex I and IV and impairment of ATP synthesis | Counteracted ruthenium red's inhibitory action complex I and IV | [15] |
| t-BHP treated mitochondrial preparations | Depletion of mitochondrial GSH; inhibition of GPx and GRd activities | Prevented the oxidation of GSH to GSSG, restored GPx and GRd back to normal | [14] |
| MPTP effect on isolated striatal synaptosomes and liver mitochondria | Inhibition of ETC complex I | Prevented MPTP-induced inhibition of complex I | [160] |
| SAMP-8 mice | Elevated lipid peroxidation products | Reduced lipid peroxidation | [122] |
| LPS-injected rats | Increased mitochondrial NOS. NO decreased ETC complex I and IV | Decreased NO production and counteracted LPS-induced inhibition of complex I an IV | [146] |
| Ischemia-reperfusion effect on mitochondria | Opens mtPT pores and destroys cardiolipin in mitochondria | Inhibits mtPT pore opening and preserves the structural complex of cardiolipin in mitochondria | [140] |
| Mitochondria from heart and diaphragm muscle of SAMP-8 mice | Increased LPO; decrease in GSH levels and GPx and GRd activities | Counteracted age-dependent increase in LPO and reduction of GSH, GPx, and GRd | [125] |
| Skeletal muscle of septic wild-type (iNOS+/+) and iNOS knockout (iNOS−/−) mice | Increase of mt iNOS and NO levels, increase of lipid peroxidation products, decrease of GSH levels and of GPx and GRd activities | Decreased mt iNOS and NO levels, counteracted reduction of GSH, GPx and GRd | [148] |
| Diaphragmatic muscle of septic wild type (iNOS+/+) and iNOS knockout (iNOS−/−) mice | Increase of mt iNOS and NO levels, reduction of GSH and of GPx and GRd activities | Decreased mt iNOS and NO levels; counteracted reduction of GSH, GPx, and GRd | [149] |
| Mitochondria from rat liver | Normal ETC function | Melatonin treatment decreased Krebs's cycle substrate-induced respiration. | [108] |
| Heart and diaphragmatic muscle of SAMP-8 mice | Decreased levels of GSH and of GPx and GRd activities, increased lipid peroxidation | Increased GSH levels and GPx and GRd activities; decreased lipid peroxidation products | [126] |
| Diaphragmatic muscle of SAMP-8 mice-effect of aging | Decrease of GSH and GPx, GRd, increase in lipid peroxidation | Counteracted age-dependent decrease in GSH, GPx, and GRd Normalized lipid peroxidation | [127] |
| Mitochondria from liver of normal mice | Normal function of ETC complexes; opening of mtPT pores after oxidative stress | Increased complex I, III, and IV; closing of the mtPT pores opened by oxidative stress | [18] |
| t-BHP effect on mitochondria of skeletal muscle | Opening of mtPT and death of myotubules | Prevented t-BHP-induced opening of mtPT pores and swelling of mitochondria | [109] |
| MPTP effect on mitochondria of neurons in substantia nigra of mice | Increased mt iNOS; increased oxidative stress | Counteracted MPTP-induced increase of iNOS in substantia nigra and reduced the oxidative stress | [161] |
| Effect of ischemia-reperfusion on mitochondria | Opening of mtPT pores and oxidation of cardiolipin | Inhibited mtPT pores and cardiolipin oxidation | [110, 143] |
| Effect of Aβ on hippocampal neurons | Inhibition of ETC; reduced ATP levels | Attenuated Aβ-induced inhibition of respiratory complexes; restored ATP levels | [187] |
Abbreviations used: Aβ: β amyloid; ETC: electron transport chain; GPx: glutathione peroxidase; GRd: glutathione reductase; GSH: reduced glutathione; GSSG: oxidized glutathione; iNOS: inducible nitric oxide synthase; LPS: lipopolysaccharide; MPTP: 1-methyl-4-phenyl-1,2,3,6 tetrahydropyridine; mt iNOS: mitochondrial inducible nitric oxide synthase; mtPT: mitochondrial permeability transition; NO: nitric oxide; SAMP-8 mice: senescence accelerated mouse; t-BHP: t-butyl hydroperoxide.