Antioxidant and Anti-inflammatory Properties Mediate the Neuroprotective Effects of Hydro-ethanolic Extract of Tiliacora triandra Against Cisplatin-induced Neurotoxicity.

BACKGROUND:Cisplatin (CDDP) is an efficacious anticancer agent used widely in chemotherapy despite its severe side effect related to neurotoxicity. Redox imbalance and inflammatory mechanism have been implicated in the pathophysiology of CDDP-induced neurotoxicity. Herein, we investigated whether Tiliacora triandra (TT) extract could inhibit  CDDP-induced redox-mediated neurotoxicity and behavioural deficit in rats. MATERIALS AND METHODS:CDDP-induced redox-mediated neurotoxicity and behavioral deficit in rats. Rats were administered TT for five consecutive weeks (250 and 500 mg/kg bw), while weekly i.p. injection of CDDP commenced on the second week (2.5 mg/kg bw) of the TT administration. RESULTS:CCDDP caused significant body weight reduction and cognitive diminution as revealed by Morris water maze and Y maze tests. In the CDDP-induced cognitive impairment (CICI) rats, there were remarkable increases in the brain levels of TNF-α, IL-6 and IL-1β and malondialdehyde (MDA), whereas catalase (CAT), glutathione (GSH), glutathione peroxidase (GPx) and superoxide dismutase (SOD) activities considerably decreased compared to normal control. The brain acetylcholinesterase (AChE) activity in CDDP control rats was significantly increased compared to the normal control. The expression of caspase-3 and p53 proteins was upregulated by CDDP injection, whereas Bcl2 was downregulated coupled with histopathological alterations in the rat brain. Interestingly, treatment with TT significantly abated neurobehavioral deficits, MDA and cytokine levels and restored CAT, GPx, GSH, SOD, and AChE activities compared to the CDDP control rats. Caspase-3 level as well as Bcl2 and p53 expressions were modulated with alleviated changes in histopathology. CONCLUSION:The findings highlight neuroprotective and cognitive function improvement efficacy of TT against CICI via redox-inflammatory balance and antiapoptotic mechanism in rats.