Melatonin attenuates brain mitochondria DNA damage induced by potassium cyanide in vivo and in vitro.
The effect of potassium cyanide on mitochondria DNA (mtDNA) in mouse brain was investigated in vivo and in vitro. When potassium cyanide (0, 0.1, 1.0 or 2.0 mM) was incubated with a crude mitochondria fraction prepared from mouse brain at 37 degrees C for 60 min, the damage of mtDNA was observed in a concentration-dependent manner. However, the mtDNA damage was prevented by a co-treatment with melatonin (1.5 mM), a scavenger of hydroxyl radicals (*OH). Furthermore, a subcutaneous injection of potassium cyanide (7mg/kg) caused both brain mtDNA damage and severe seizures in mouse. The damage of mtDNA and seizures induced by potassium cyanide were abolished by the pre-injection of melatonin (20 mg/kg). Hydrogen peroxide (1.5 mM) inflicted damage to brain mtDNA in the presence of Fe(2+) (3.0 microM). The damage was abolished by the co-treatment with melatonin. Furthermore, when cyanide (0, 0.1 or 1.0 mM) was incubated with the crude mitochondria fraction prepared from mouse brain, the lipid peroxidation was significantly increased in a concentration-dependent manner. The increased lipid peroxidation was completely inhibited by the co-treatment with melatonin (1.0 mM). These results suggest that reactive oxygen species including the *OH may play a cardinal role for mtDNA damage induced by potassium cyanide. Hence, the present study concluded that melatonin protects against DNA damage induced by the *OH produced by cyanide or hydrogen peroxide.
Yamamoto
Hiro-aki
HA
University of Tsukuba, Institute of Community Medicine, Tsukuba, Ibaraki, Japan. aml05664@mail1.accsnet.ne.jp
Mohanan
Parayanthala V
PV
D000818:Animals; D001923:Brain Chemistry / Q000187:drug effects*; D004249:DNA Damage / Q000187:drug effects*; D004272:DNA, Mitochondrial / Q000187:drug effects*; D004587:Electrophoresis, Agar Gel; D016166:Free Radical Scavengers / Q000494:pharmacology*; D006861:Hydrogen Peroxide / Q000633:toxicity; D066298:In Vitro Techniques; D007501:Iron / Q000633:toxicity; D015227:Lipid Peroxidation / Q000187:drug effects; D008297:Male; D008550:Melatonin / Q000494:pharmacology*; D051379:Mice; D011190:Potassium Cyanide / Q000037:antagonists & inhibitors* / Q000633:toxicity*; D012640:Seizures / Q000139:chemically induced
D004272:DNA, Mitochondrial; D016166:Free Radical Scavengers; D006861:Hydrogen Peroxide; D007501:Iron; D008550:Melatonin; D011190:Potassium Cyanide