Superoxide radical scavenging and attenuation of hypoxia-reoxygenation injury by neurotransmitter ferric complexes in isolated rat hepatocytes.
Reactive oxygen species have been implicated in the pathogenesis of hypoxia-reoxygenation injury. Previously, we demonstrated that 2:1 catecholic iron complexes were more effective than uncomplexed catechols at (a) scavenging superoxide radicals generated enzymatically, and (b) protecting hepatocytes against hypoxia-reoxygenation injury [25]. Based on these findings, we sought to demonstrate similar effects using catecholamine neurotransmitters. Various catecholamine-iron complexes were shown to be more effective than uncomplexed catecholamines at scavenging superoxide radicals and could be used to protect cells from hypoxia-reoxygenation injury. alpha-Methyl-3, 4-dihydroxyphenylalanine (alpha-methylDOPA) complexed with ferric ion (2:1) showed the greatest superoxide scavenging potency amongst the catecholamine-iron complexes. The uncomplexed catecholamines were much less effective at scavenging superoxide radicals than the iron-catecholamine complexes. Dopamine was the most effective superoxide scavenger among the uncomplexed catecholamines. The superoxide scavenging effectiveness of the latter seemed to correlate with their reduction potentials, but not directly to their pK(a) values. Furthermore, dopamine:iron(III) complex protected isolated hepatocytes against hypoxia-reoxygenation injury at concentrations four-fold lower than that required for protection by dopamine alone.
Siraki
A G
AG
Faculty of Pharmacy, University of Toronto, 19 Russell Street, M5S 2S2, Toronto, Canada.
Smythies
J
J
O'Brien
P J
PJ
D015102:3,4-Dihydroxyphenylacetic Acid / Q000494:pharmacology; D000332:Aerobiosis; D000818:Animals; D002395:Catecholamines / Q000494:pharmacology*; D015687:Cell Hypoxia / Q000502:physiology*; D002712:Chlorides; D004298:Dopamine / Q000494:pharmacology; D004837:Epinephrine / Q000494:pharmacology; D005290:Ferric Compounds / Q000494:pharmacology*; D016166:Free Radical Scavengers / Q000494:pharmacology*; D022781:Hepatocytes / Q000166:cytology* / Q000187:drug effects / Q000502:physiology*; D008099:Liver / Q000166:cytology; D008750:Methyldopa / Q000494:pharmacology; D018377:Neurotransmitter Agents / Q000494:pharmacology*; D009638:Norepinephrine / Q000494:pharmacology; D010101:Oxygen Consumption / Q000187:drug effects; D051381:Rats; D017207:Rats, Sprague-Dawley; D012701:Serotonin / Q000494:pharmacology; D013481:Superoxides / Q000378:metabolism*
D002395:Catecholamines; D002712:Chlorides; D005290:Ferric Compounds; D016166:Free Radical Scavengers; D018377:Neurotransmitter Agents; D015102:3,4-Dihydroxyphenylacetic Acid; D013481:Superoxides; D012701:Serotonin; D008750:Methyldopa; C024555:ferric chloride; D004298:Dopamine; D009638:Norepinephrine; D004837:Epinephrine