Effect of lycopene and β-carotene on peroxynitrite-mediated cellular modifications

• Published in: Toxicology and applied pharmacology 2006-09, Vol.215 (3), p.330-340
• Main Authors: Muzandu, Kaampwe, Ishizuka, Mayumi, Sakamoto, Kentaro Q., Shaban, Zein, El Bohi, Khlood, Kazusaka, Akio, Fujita, Shoichi
• Format: Article
• Language: English
• Subjects: Animals; Antioxidants - pharmacology; beta Carotene - pharmacology; Biological and medical sciences; Carotenoids - pharmacology; Cell Line; Cell Survival; Comet Assay; Cricetinae; Cricetulus; DNA damage; DNA Damage - drug effects; Lycopene; Medical sciences; Molsidomine - analogs & derivatives; Molsidomine - toxicity; Nitric Oxide Donors - toxicity; Peroxynitrite; Peroxynitrous Acid - toxicity; Protein tyrosine nitration; Toxicology; Tyrosine - analogs & derivatives; Tyrosine - metabolism; β-carotene
• ISSN: 0041-008X; 1096-0333
• DOI: 10.1016/j.taap.2006.03.006

Peroxynitrite formed by the reaction of superoxide and nitric oxide is a highly reactive species with a role in various pathological processes such as cancer, chronic inflammation, and cardiovascular and neurological diseases. In the present study, the effect of the carotenoids, lycopene and β-carotene, on peroxynitrite-mediated modifications in plasmid DNA as well as cellular DNA and proteins were investigated. In pUC18 plasmid DNA, these carotenoids strongly inhibited DNA strand breaks caused by peroxynitrite generated from 3-morpholinosydnonimine (SIN-1). SIN-1 was also used to determine effects on DNA damage and protein tyrosine nitration in Chinese hamster lung fibroblasts. SIN-1 dose-dependently increased nitration of proteins in cells above basal levels as determined by Western blotting. This nitration was inhibited in the presence of the uric acid as well as lycopene. Physiological concentrations (0.31–10 μM) of lycopene and β-carotene also had protective effects on DNA damage, as measured by the comet assay. Lycopene significantly reduced DNA damage particularly, in the median range of concentrations (2.5 μM). The protective effects of lycopene and β-carotene could be due to their scavenging of reactive oxygen (ROS) and/or nitrogen species (RNS) as they reduce the amount of intracellular ROS/RNS produced following treatment with SIN-1 by as much as 47.5% and 42.4%, respectively. The results obtained in this study suggest that carotenoids may alleviate some of the deleterious effects of peroxynitrite and possibly other reactive nitrogen species as well in vivo.