Department of Functional and Analytical Food Sciences, Niigata University of Pharmacy & Applied Life Sciences (NUPALS), Niigata City, Japan.
Free Radic Res. 2012 Jan;46(1):50-60. doi: 10.3109/10715762.2011.638291.
This study aimed to investigate the potential beneficial effect of an antioxidant lignan, Schisandrin B (Sch B), against cisplatin (cDDP) induced oxidative stress mediated geno- and neuro-toxicities. A dose of 10 mg/kg cDDP induced considerable genotoxicity in mice, and Sch B treatment attenuated the cDDP-induced DNA damage as assessed by the comet assay in the brain. The frequency of micro-nucleated erythrocyte production in bone marrow was also significantly reduced by Sch B treatment in cDDP-treated mice. In neurobehavioral studies, Sch B significantly prevented the memory deficits induced by cDDP, and had an anxiolytic effect in the elevated plus maze task. Sch B treatment significantly attenuated lipid peroxidation, acetylcholinesterase activity and nitrite levels induced by cDDP. Furthermore, Sch B effectively inhibited NF-κB and p53 activation, and cleaved caspase-3 expression in cDDP-treated mice. Hence, Sch B with potent antioxidant and neuro-protective property with no mutagenic activity would be beneficial complementary food factor against cDDP induced oxidative stress.
本研究旨在探讨抗氧化木脂素五味子丙素(Sch B)对顺铂(cDDP)诱导的氧化应激介导的遗传和神经毒性的潜在有益作用。10mg/kg 的 cDDP 剂量在小鼠中引起了相当大的遗传毒性,而 Sch B 处理可减轻彗星试验评估的大脑中 cDDP 诱导的 DNA 损伤。Sch B 处理还可显著降低 cDDP 处理小鼠骨髓中微核红细胞的产生频率。在神经行为研究中,Sch B 可显著预防 cDDP 诱导的记忆缺陷,并在高架十字迷宫任务中具有抗焦虑作用。Sch B 处理可显著抑制 cDDP 诱导的脂质过氧化、乙酰胆碱酯酶活性和亚硝酸盐水平。此外,Sch B 可有效抑制 cDDP 处理小鼠中 NF-κB 和 p53 的激活以及半胱天冬酶-3 的表达。因此,具有强大抗氧化和神经保护作用且无致突变活性的 Sch B 将是对抗 cDDP 诱导的氧化应激的有益补充食物因子。