Tropisetron attenuates amyloid‐beta‐induced inflammatory and apoptotic responses in rats

• DOI: 10.1111/eci.12141
• Publication Date: 2013-07-12T12:53:33Z
• Authors: Reza Rahimian; Gohar Fakhfouri; Shahram Ejtemaei ...; Jean‐Eric Ghia; Armando A. Genazzani; Borna Payandemehr; Ahmad Reza Dehpour; Kazem Mousavizadeh; Dmitry Lim
• Keywords: Tropisetron; Amyloid beta

Abstract Background Alzheimer's disease ( AD ) is a neurodegenerative disorder featured by deposition of beta‐amyloid (Aβ) plaques in the hippocampus and associated cortices progressive cognitive decline. Tropisetron, selective 5‐ HT 3 receptor antagonist, conventionally used to counteract chemotherapy‐induced emesis. Recent investigations describe antiphlogistic properties for tropisetron. It has been shown that tropisetron protects against rat embolic stroke. We investigated protective model possible involvement receptors. Material methods Aβ (1–42) was injected into male rats. Animals were treated intracerebroventricularly with tropisetron, mCPBG (selective 5‐HT agonist) or plus on days 1, 3, 5 7. Seven following administration, inflammatory markers (TNF‐α, COX‐2, iNOS NF‐κB), apoptotic (caspase cytochrome c release) calcineurin phosphatase activity assessed hippocampus. Results inoculation, control animals displayed dramatic increase TNF‐α, , NF‐κB, active caspase release Tropisetron significantly diminished elevated levels these reversed deficit. Interestingly, also found be potent inhibitor activity. The agonist when co‐administered completely procognitive anti‐apoptotic while it could only partially anti‐inflammatory effects. alone aggravated Aβ‐induced injury. Conclusion Our findings indicate neurotoxicity vivo through both receptor‐dependent independent pathways.