Nordihydroguaiaretic acid is a potent in vitro scavenger of peroxynitrite, singlet oxygen, hydroxyl radical, superoxide anion and hypochlorous acid and prevents in vivo ozone-induced tyrosine nitration in lungs

Abstract

The antioxidant nordihydroguaiaretic acid (NDGA) has recently become well known as a putative anticancer drug. In this paper, it was evaluated the in vitro peroxynitrite (ONOO− ), singlet oxygen (1O2), hydroxyl radical (OH√), hydrogen peroxide (H2O2), superoxide anion and hypochlorous acid (HOCl) scavenging capacity of NDGA. It was found that NDGA scavenges: (a) ONOO− (IC50 = 4 ± 0.94 μM) as efficiently as uric acid; (b) 1O2 (IC50 = 151 ± 20 μM) more efficiently than dimethyl thiourea, lipoic acid, N-acetyl-cysteine and glutathione; (c) OH√ (IC50 = 0.15 ± 0.02 μM) more efficiently than dimethyl thiourea, uric acid, trolox, dimethyl sulfoxide and mannitol, (d) (IC50 = 15 ± 1 μM) more efficiently than N-acetyl-cysteine, glutathione, tempol and deferoxamine and (e) HOCl (IC50 = 622 ± 42 μM) as efficiently as lipoic acid and N-acetyl-cysteine. NDGA was unable to scavenge H2O2. In an in vivo study in rats, NDGA was able to prevent ozone-induced tyrosine nitration in lungs. It is concluded that NDGA is a potent in vitro scavenger of ONOO− , 1O2, OH√, and HOCl and is able to prevent lung tyrosine nitration in vivo.