Kawata Akifumi, Murakami Yukio, Suzuki Seiji, Fujisawa Seiichiro
Division of Oral Diagnosis and General Dentistry, Department of Diagnostic and Therapeutic Sciences, Meikai University School of Dentistry, Sakado, Japan.
Division of Oral Diagnosis and General Dentistry, Department of Diagnostic and Therapeutic Sciences, Meikai University School of Dentistry, Sakado, Japan
In Vivo. 2018 Mar-Apr;32(2):255-264. doi: 10.21873/invivo.11232.
BACKGROUND/AIM: 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.
背景/目的:多烯类胡萝卜素β-胡萝卜素和番茄红素是抗氧化剂,不仅能淬灭单线态氧,还能抑制脂质过氧化。三丁基硼烷(TBB)用作牙科树脂材料的引发剂,与氧气和活性氧(ROS)反应性极强。TBB的这种反应性可能与类胡萝卜素与ROS的反应性类似。为阐明此类ROS清除剂的生物活性,我们从脂多糖(LPS)诱导的环氧合酶-2(Cox2)、一氧化氮合酶2(Nos2)和肿瘤坏死因子-α(Tnfa)的RNA表达,以及RAW264.7细胞中血红素加氧酶1(Hmox1)mRNA的表达和上调方面,研究了β-胡萝卜素、番茄红素和TBB的抗炎活性。
使用实时逆转录聚合酶链反应(PCR)研究mRNA表达。在偶氮二异丁腈或过氧化苯甲酰-甲基丙烯酸甲酯体系中,采用诱导期法评估类胡萝卜素的抗氧化活性。
100μM的β-胡萝卜素和番茄红素以及0.125%的TBB可上调Hmox1 mRNA,但不能上调Cox2和Nos2 mRNA。50μM的β-胡萝卜素和番茄红素以及0.5 - 1%的TBB可抑制LPS刺激的Cox2、Nos2和Tnfa基因表达。β-胡萝卜素和番茄红素均具有较弱的抗氧化活性,但β-胡萝卜素在较高浓度时表现出促氧化活性。
β-胡萝卜素、番茄红素和TBB的抗炎活性可能与其ROS清除活性有关。此外,类胡萝卜素和TBB的活性可能分别归因于ROS诱导的类胡萝卜素中间体和硼烷的亲电性。鉴于它们上调Hmox1 mRNA表达,其抗炎活性可能归因于亲电试剂/抗氧化反应元件转录系统效能的增强。