Possible role of apoptosis and autophagy on mediation of tramadol induced neurodegeneration in rat hippocampus

Abstract

Abstract Background Tramadol (TRA) is a pain killer, which its abuse is widely increased during recent years, but clear mechanism for induction of neurotoxicity remains unclear. The present study aims to investigate involvement of apoptosis and autophagy signaling pathways and also mitochondrial system on TRA induced neurotoxicity. Materials and Methods Sixthy adult male rats were randomly divided into five groups that received standard saline and TRA in doses of 25, 50, 75, 100 and 150 mg/kg as intraperitoneal administration for 21 days, respectively. In 22th day, Open Field Test (OFT), as standard test for hippocampal cell damages was used. Also hippocampal level of JNK, Bcl-2, Beclin1 and Bax proteins as well as mitochondrial quadruple complex enzymes was measured Results TRA at doses 75,100 and 150 mg/kg causes dysfunction in OFT behavioral and also in mentioned high doses could increases level of both activated (total) and non-activated from of JNK and also increased Beclin-1 and Bax. TRA at doses of 75,100 and 150 mg/kg increased phosphorylated form of Bcl-2 level while decreased un-phosphorylated (total form) form of Bcl-2. Conclusion According to obtained data, TRA causes activation of apoptosis and or autophagy processes via modulation of TNF-α or IL-1β/JNK/Bcl-2/Beclin1 and Bcl-2/Bax signaling pathway and causes dysfunction of mitochondrial respiratory chain enzymes.