Anti-inflammatory Activity of β-Carotene, Lycopene and Tri-n-butylborane, a Scavenger of Reactive Oxygen Species.

Abstract

The polyene carotenoids β-carotene and lycopene are antioxidants that not only quench singlet oxygen but also inhibit lipid peroxidation. Tri-n-butyl borane (TBB) is used as an initiator for dental resin materials and is extremely reactive with oxygen and reactive oxygen species (ROS). This reactionability of TBB may be analogous to that of carotenoids with ROS. To clarify the biological activity of such ROS scavengers, we investigated the anti-inflammatory activity of β-carotene, lycopene and TBB in terms of the expression of RNA for lipopolysaccharide (LPS)-induced cyclooxygenase-2 (Cox2), nitric oxide synthase 2 (Nos2) and tumor necrosis factor-alpha (Tnfa), and mRNA expression and up-regulation of heme oxygenase 1 (Hmox1) mRNA in RAW264.7 cells. mRNA expression was investigated using real-time reverse transcriptase-polymerase chain reaction (PCR). The antioxidant activity of carotenoids was evaluated using the induction period method in the azobisisobutyronitrile or benzoyl peroxide-methyl methacrylate system. Hmox1 mRNA, but not Cox2 and Nos2 mRNA, was up-regulated by 100 μM β-carotene and lycopene, and by 0.125% TBB. LPS-stimulated Cox2, Nos2 and Tnfa gene expression was inhibited by 50 μM β-carotene and lycopene, and by 0.5-1% TBB. Both β-carotene and lycopene had weak antioxidant activity, but β-carotene showed pro-oxidant activity at higher concentrations. The anti-inflammatory activity of β-carotene, lycopene and TBB may be related to their ROS-scavenging activity. Additionally, the activity of carotenoids and TBB may be attributed to the electrophilicity of ROS-induced carotenoid intermediates and boranes, respectively. Their anti-inflammatory activity may be attributable to enhancement of the potency of the electrophile/antioxidant response element transcription system in view of their up-regulation of Hmox1 mRNA expression.