The toxic profile of tramadol combined with nicotine on the liver and testicles: evidence from endoplasmic reticulum stress.

Abstract

Tramadol is one of the most commonly abused substances in the Middle East. Furthermore, smoking is extremely common among the population. An experimental study was performed on Sprague-Dawley rats to explore the effects of both nicotine and tramadol on the liver and testes. The tramadol was administered at 10 and 20mg/kg, respectively, while the nicotine was administered at 125mg/kg. Histological examination and androgen receptor ELISA assay showed mild effects on the liver and proofed safety on the testis. Western blot analysis of BIP (immunoglobulin heavy-chain binding protein) and CHOP (CCAAT-enhancer-binding protein homologous protein) revealed that fewer problems were induced by adding nicotine to tramadol. Autophagy marker LCIII and apoptosis marker caspase-8 showed similar effects to CHOP and BIP on liver samples. The real-time PCR of BIP expression showed similar but not identical results. The results showed mild endoplasmic reticulum stress, autophagy, and apoptosis in the liver samples. Histological examination revealed stable spermatogenesis with average androgen receptor blood levels in the different groups.