Role of apoptosis and autophagy in mediating tramadol-induced neurodegeneration in the rat hippocampus.

Mol Biol Rep

Chronic Respiratory Disease Research Center (CRDRC), National Research Institute of Tuberculosis and Lung Diseases (NRITLD), Shahid Beheshti University of Medical Sciences, Tehran, Iran.

Published: September 2023

Background: Tramadol (TRA) is an analgesic prescribed for treating mild to moderate pains, the abuse of which has increased in recent years. Chronic tramadol consumption produces neurotoxicity, although the mechanisms are unclear. The present study investigated the involvement of apoptosis and autophagy signaling pathways and the mitochondrial system in TRA-induced neurotoxicity.

Materials And Methods: Sixty adult male Wistar rats were divided into five groups that received standard saline or TRA in doses of 25, 50, 75, 100, or 150 mg/kg intraperitoneally for 21 days. On the 22nd day, the Open Field Test (OFT) was conducted. Jun N-Terminal Kinase (JNK), B-cell lymphoma-2 (Bcl-2), Beclin1, and Bcl-2-like protein 4 (Bax) proteins and tumor necrosis factor α (TNF-α) and interleukin 1β (IL-1β) were measured in rat hippocampal tissue.

Results: TRA at doses 75, 100, and 150 mg/kg caused locomotor dysfunction in rats and increased total and phosphorylated forms of JNK and Beclin-1, Bax, and Caspase-3. TRA at the three higher doses also increased the phosphorylated (inactive) form of Bcl-2 level while decreasing the unphosphorylated (active) form of Bcl-2. Similarly, the protein levels of TNF-α and IL-1β were increased dose-dependently. The mitochondrial respiratory chain enzymes were reduced at the three higher doses of TRA.

Conclusion: TRA activated apoptosis and autophagy via modulation of TNF-α or IL-1β/JNK/Bcl-2/Beclin1 and Bcl-2/Bax signaling pathways and dysfunction of mitochondrial respiratory chain enzymes.

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Source
http://dx.doi.org/10.1007/s11033-023-08641-9DOI Listing

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