title: Acutely administered melatonin restores hepatic mitochondrial physiology in old mice.
abstract: Damage to mitochondria as a result of the intrinsic generation of free radicals is theoretically involved in the processes of cellular aging. Herein, we investigated whether acutely administered melatonin, due to its free radical scavenging activity, would influence mitochondrial metabolism. Mitochondrial respiratory activity and respiratory chain complex I and IV activities in liver mitochondria from a strain of senescence-accelerated-prone mice (SAMP8) and a strain of senescence-accelerated-resistant mice (SAMR1) were measured when the animals were 12 months of age. Respiratory control index (RCI), ADP/O ratio, State 3 respiration and dinitrophenol (DNP)-dependent uncoupled respiration were significantly lower in SAMP8 than in SAMR1. In contrast, State 4 respiration was significantly higher in SAMP8 than in SAMR1. Activities of complexes I and IV in SAMP8 were significantly lower than in SAMR1. Melatonin administration (10mg/kg body weight, intraperitoneally) 1h prior to sacrifice significantly increased RCI, ADP/O ratio, State 3 respiration and DNP-induced uncoupled respiration in SAMP8 while also significantly reducing State 4 respiration in SAMP8. The injection of melatonin also significantly increased complex I activity in both mouse strains and complex IV activity in the liver of SAMP8 mice. These results document an age-related decrease in hepatic mitochondrial function in SAM which can be modified by an acute pharmacological injection of melatonin; the indole stimulated mitochondrial respiratory chain activity which would likely reduce deteriorative oxidative changes in mitochondria that normally occur in advanced age.
authors.affiliation: Department of Clinical Nursing Science, Kochi Medical School, Oko, Nankoku, Kochi 783-8505, Japan. okataniy@med.kochi-ms.ac.jp
authors.forename: Yuji
authors.initials: Y
authors.lastname: Okatani
authors.forename: Akihiko
authors.initials: A
authors.lastname: Wakatsuki
authors.forename: Russel J
authors.initials: RJ
authors.lastname: Reiter
authors.forename: Yasuyo
authors.initials: Y
authors.lastname: Miyahara
mesh_terms: D000375:Aging; D000818:Animals; D000975:Antioxidants / Q000494:pharmacology; D016922:Cellular Senescence; D004579:Electron Transport; D005260:Female; D005609:Free Radicals; D008099:Liver / Q000378:metabolism / Q000502:physiology*; D008297:Male; D008550:Melatonin / Q000008:administration & dosage / Q000494:pharmacology*; D051379:Mice; D008928:Mitochondria; D008930:Mitochondria, Liver / Q000378:metabolism*; D010100:Oxygen / Q000378:metabolism; D010101:Oxygen Consumption; D010766:Phosphorylation; D013997:Time Factors
chemical_list: D000975:Antioxidants; D005609:Free Radicals; D008550:Melatonin; D010100:Oxygen