Combining Low toxic dose Tramadol and smoking is relatively safe unless you stop them: An Animal model evidence of Endoplasmic reticulum stress

Low toxic doses of tramadol induced animal brain cortex apoptosis and hippocampus injury. Adding nicotine reverted hippocampus pathological changes without triggering brain injury. The expression of CHOP protein in real-time PCR showed mild Endoplasmic reticulum stress (ER) in rats’ brains. Histological, immunohistochemical, and western blotting analysis of CHOP and BIP chaperones demonstrated Endoplasmic reticulum stress in brain and liver tissue samples. Furthermore, the levels of apoptosis and autophagy markers demonstrated a mild increase. Adding Nicotine relatively decreasedbrain and liver ER stress. The combined profile was considerably protective in comparison to administering each drug separately. Mild ER stress is essential for normal cell functions. The blood level of serotonin was high in all study groups with a marked increase in its level when tramadol and nicotine were combined. Low toxic doses of tramadol in combination with nicotine were safe at the reproductive system level which was evaluated by histological examination and animal blood androgen assay. Generally, combining low-dose tramadol with smoking was found to be safe in various animal tissues and organs, however, the high serotonin level in the blood can be critical and associated with a high risk of serious withdrawal and pathological consequences. Serotonin receptor blockers such as olanzapine may increase systemic serotonin levels and need further investigation to utterly pinpoint their roles in managing mood disorders.