a Histopathological and Immunohistochemical Study of Adult rats’ Brain after Long-term Exposure to Amadol (Tramadol Hydrochloride)

Tramadol hydrochloride (TH) is an atypical opioid synthetic agent which is a centrally acting analgesic,used for treating moderate to severe pain with fewer side effects than traditional opioid medications.The present work aimed to study the dose-dependent possible deleterious effect of long-term administrationof TH as well as a 4-weeks spontaneous recovery period to evaluate the reversibility of the toxic effectson the brain tissues of the rats. Forty adult male albino rats were divided into 4 groups. Group I(control), group II (low dose) was treated orally with TH (30 mg/kg/day) and group III (high dose) wastreated orally with TH (60 mg/kg/day) for 4 weeks. Group IV (follow up) was treated as group III andthen held for 4-weeks recovery period. At the end of experimental period, rats were sacrificed, histopathologicaland immunohistolochemical (IHC) examinations of the brains were carried out. The obtained resultsrevealed that both low and high doses of TH produced remarkable histomorphological changes inrats’ brains (cerebral cortex {CC} and hippocampus {HC}) as compared to control and were more pronouncedin high than low dose group and in both doses when compared to that of control. On the otherhand, group IV showed remarkable regression of the total degenerative changes induced by TH withsome residual effect. This was noted by nearly normal morphology of brain tissues and marked significantdecrease of p53 and Bax along with significant increase of Bcl-2 protein expressions when comparedto those of group II and III treated rates.