Role of oxidative stress and mitochondrial dysfunction in tolerance induced by chronic administration of tramadol in male rat

Nowadays, tramadol (Tra) is a widely use opioid because of its fewer side effects than the other opioids. However, long- term administration of Tra has potential ability to develop tolerance. Hence, this work was designed to investigate the role of oxidative stress and mitochondrial dysfunction in tramadol induced tolerance in rats.Method: Male wistar rats were randomly divided into four groups (six per each). Tramadol groups received the drug intraperitoneally at doses of 25, 50 and 75 mg/kg/day for 21 days respectively and control group (normal saline). Tramadol tolerance measured by hot plate and tail flick tests at first, fifth, tenth, fiftieth and twenty first days of treatment. Rats were sacrificed after 24h of last injection. Brain tissue was isolated for evaluation of pathologic analysis, oxidative stress and mitochondrial damage biomarkers included: reactive oxygen species (ROS), glutathione (GSH), lipid peroxidation (LPO), protein carbonyl (PC), super oxide dismutase (SOD), mitochondrial swelling and MTT.Result: The chronic exposure of Tra led to brain commitment, as shown by increasing MDA, ROS formation, PC and decreasing SOD activity and decreasing GSH concentration. Additionally, increasing MTT and mitochondrial swelling were shown mitochondrial dysfunction in brain. Hence, response temperature to each of Tra groups were significantly decrees in fifth and twenty first day as compare to first day of each groups. Histopathological finding was included degeneration of neurons, hemorrhage and inflammation in brain tissue.Conclusion: Our finding suggested tolerance in chronic administration of tramadol maybe accrue via oxidative stress and mitochondrial dysfunction in male rats.

کلیدواژه ها:

Tramadol ، Tolerance ، Oxidative stress ، Mitochondria