145. Schisandrin B, attenuates cisplatin-induced oxidative stress, genotoxicity and neurotoxicity through modulation of NF-κB/p53 pathway in mice.

Giridharan VV[1], Thandavarayan RA[1], Bhilwade HN[2], Ko KM[3], Watanabe K[4], Konishi T[1]

[1] Department of Functional and Analytical Food Sciences, Niigata University of Pharmacy & Applied Life Sciences (NUPALS), Niigata City, Japan.
[2] Radiation Biology and Health Sciences Division, Bhabha Atomic Research Centre, Mumbai, India.
[3] Division of Life Science, Hong Kong University of Science and Technology, Hong Kong SAR, China.
[4] Department of Clinical Pharmacology, NUPALS, Niigata City, Japan

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.