Abstract
The unregulated oxidative modification of biological molecules has been implicated in the pathogenesis of various diseases, and the beneficial effects of antioxidants against detrimental oxidation have received much attention. Among the multiple oxidants, peroxyl radical and peroxynitrite play an important role as chain-carrying species in lipid peroxidation and one of the major oxidants produced in vivo, respectively. This study was performed to elucidate the prominent features of these two oxidants by comparing their reactivity and selectivity and also the effects of antioxidants against plasma lipid oxidation induced by the two oxidants. It was shown that despite peroxyl radical and peroxynitrite gave similar pattern of lipid peroxidation products of plasma, and these two oxidants exert different selectivity and reactivity towards probes and antioxidants. The capacity of antioxidants to scavenge peroxynitrite and peroxyl radical decreased in the order BSA > glutathione > α-tocopherol ∼ bilirubin ∼ α − tocotrienol > γ-tocotrienol ∼ γ − tocopherol > uric acid and α-tocopherol ∼ α − tocotrienol > bilirubin > γ-tocotrienol ∼ γ − tocopherol > BSA > glutathione > uric acid, respectively. α-Tocopherol localised within plasma lipoproteins was six times less effective than trolox in aqueous phase for scavenging peroxynitrite and the derived oxidants, despite the same chemical reactivity of the two chromanols. BSA was relatively more effective as antioxidant against peroxynitrite than peroxyl radical, whereas TEMPO did not act as efficient antioxidant against both oxidants. It was suggested that thiols act as more potent antioxidant against peroxynitrite than phenolic antioxidants, while phenolic antioxidants are potent inhibitor of lipid peroxidation induced by free radicals including those derived from peroxynitrite.
Abbreviations: AAPH: 2,2’-azobis(2-amidinopropane) dihydrochloride; C11-BODIPY: 4,4-difluoro-5-(4-phenyl-1,3-butadienyl)-4-bora-3a,4a-diaza-s-indacene-3-undecanoic acid; BSA: bovine serum albumin; DPPP: diphenyl-1-pyrenylphosphine; H(p)ODE: hydro(pero)xyoctadecadienoates; PGR: pyrogallol red; PUFA: polyunsaturated fatty acid; SIN-1: 3-morpholinosydnonimine; TEMPO: 2,2-6,6 tetramethylpiperidine-1-oxyl; Trolox: 2-carboxy-2,5,7,8-tetramethyl-6-hydroxychroman
Disclosure statement
Yuji Naito received scholarship fund from EA Pharma. Co. Ltd and collaboration research fund from Fujifilm Medical Co., Ltd. and Taiyo Kagaku Co., Ltd., and has been paid lecture fees by Mylan EPD Co., Takeda Pharma. Co. Ltd, Mochida Pharma. Co. Ltd., EA pharma. Co. Ltd, Otsuka Pharma. Co. Ltd, Nippon Kayaku Co. Ltd., and Miyarisan Pharma. Co. Ltd. The present research was partly funded by these funds. Neither the funding agency nor any outside organisation has participated in study design or has any competing interest. These companies had final approval of the manuscript.