Nordihydroguaiaretic acid is a potentin vitroscavenger of peroxynitrite, singlet oxygen, hydroxyl radical, superoxide anion and hypochlorous acid and preventsin vivoozone-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.