Hypochlorous acid-induced zinc release from thiolate bonds: a potential protective mechanism towards biomolecules oxidant damage during inflammation.
It has been proposed that metalloprotein zinc mobilization mediated by hypochlorous acid (HOCl) may induce cell injury (see H. Fliss and M. Ménard (1991), Archives of Biochemistry and Biophysics, 287, 175-179). In the present paper, we have demonstrated using a dimercaptopropanol-zinc complex that, once released from thiolate bonds by HOCl, zinc can exert a significant antioxidant effect on both linolenic acid and deoxyribose oxidation induced by iron. In these experimental conditions, however, the antagonism towards deoxyribose oxidation is notably less than that towards linolenic acid peroxidation, thus suggesting a more specific inhibitory effect of zinc on iron-mediated oxidant damage when polyunsaturated fatty acids represent the oxidizable substrate. The antioxidant effects of zinc are strictly related to the "free" form; indeed, the dimercaptopropanol-zinc complex per se is stimulatory even on biomolecules oxidant damage, apparently as a result of the prooxidant prooxidant interaction of the thiol compound with iron. In light of these results, it may be proposed that the zinc released from thiolate bonds by HOCl could specifically limit tissue oxidative burden in pathological conditions involving neutrophil accumulation and activation, such as inflammation and ischemia-reperfusion.
Lapenna
D
D
Cattedra di Patologia Speciale Medica, Università G. D'Annunzio, Facolta' di Medicina e Chirurgia, Chieti, Italy.
De Gioia
S
S
Ciofani
G
G
Mezzetti
A
A
Consoli
A
A
Di Ilio
C
C
Cuccurullo
F
F
D000818:Animals; D000975:Antioxidants; D003855:Deoxyribose; D004112:Dimercaprol / Q000031:analogs & derivatives*; D006801:Humans; D006861:Hydrogen Peroxide; D006997:Hypochlorous Acid; D007249:Inflammation / Q000503:physiopathology*; D007501:Iron; D009942:Organometallic Compounds; D016877:Oxidants / Q000633:toxicity*; D015032:Zinc; D017962:alpha-Linolenic Acid
D000975:Antioxidants; D009942:Organometallic Compounds; D016877:Oxidants; D004112:Dimercaprol; D017962:alpha-Linolenic Acid; D003855:Deoxyribose; D006997:Hypochlorous Acid; C088066:dimercaptopropanol-zinc complex; D006861:Hydrogen Peroxide; D007501:Iron; D015032:Zinc