Free radical scavenging action of the natural polyamine spermine in rat liver mitochondria.
The isoflavonoid genistein, the cyclic triterpene glycyrrhetinic acid, and salicylate induce mitochondrial swelling and loss of membrane potential (Delta Psi) in rat liver mitochondria (RLM). These effects are Ca(2+)-dependent and are prevented by cyclosporin A and bongkrekik acid, classic inhibitors of mitochondrial permeability transition (MPT). This membrane permeabilization is also inhibited by N-ethylmaleimide, butylhydroxytoluene, and mannitol. The above-mentioned pro-oxidants also induce an increase in O(2) consumption and H(2)O(2) generation and the oxidation of sulfhydryl groups, glutathione, and pyridine nucleotides. All these observations are indicative of the induction of MPT mediated by oxidative stress. At concentrations similar to those present in the cell, spermine can prevent swelling and Delta Psi collapse, that is, MPT induction. Spermine, by acting as a free radical scavenger, in the absence of Ca(2+) inhibits H(2)O(2) production and maintains glutathione and sulfhydryl groups at normal reduced level, so that the critical thiols responsible for pore opening are also consequently prevented from being oxidized. Spermine also protects RLM under conditions of accentuated thiol and glutathione oxidation, lipid peroxidation, and protein oxidation, suggesting that its action takes place by scavenging the hydroxyl radical.
Sava
Irina G
IG
Unità per lo Studio delle Biomembrane, Istituto di Neuroscienze del CNR, Dipartimento di Chimica Biologica, Università di Padova, Viale G. Colombo 3, 35121 Padova, Italy.
Battaglia
Valentina
V
Rossi
Carlo A
CA
Salvi
Mauro
M
Toninello
Antonio
A
D000818:Animals; D002118:Calcium / Q000494:pharmacology; D016166:Free Radical Scavengers / Q000378:metabolism / Q000494:pharmacology*; D005978:Glutathione / Q000378:metabolism; D006034:Glycyrrhetinic Acid / Q000633:toxicity; D017665:Hydroxyl Radical / Q000378:metabolism; D066298:In Vitro Techniques; D015227:Lipid Peroxidation / Q000187:drug effects; D008564:Membrane Potentials / Q000187:drug effects; D008930:Mitochondria, Liver / Q000187:drug effects* / Q000378:metabolism; D008933:Mitochondrial Swelling / Q000187:drug effects; D016877:Oxidants / Q000633:toxicity; D018384:Oxidative Stress; D051381:Rats; D013096:Spermine / Q000378:metabolism / Q000494:pharmacology*; D013438:Sulfhydryl Compounds / Q000378:metabolism
D016166:Free Radical Scavengers; D016877:Oxidants; D013438:Sulfhydryl Compounds; D013096:Spermine; D017665:Hydroxyl Radical; D005978:Glutathione; D006034:Glycyrrhetinic Acid; D002118:Calcium