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

Abstract

Background: Tramadol is one of the most commonly abused substances in the Middle East. Furthermore, smoking is extremely common among the population.

Methods: 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 20 mg/kg, respectively, while the nicotine was administered at 125 mg/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.

Conclusions: 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.

Keywords: BIB; CHOP; Endoplasmic reticulum stress; Liver; Nicotine; Testis; Tramadol.