Histopathological Changes in Brain Tissues Associated with Oral Administration of Tramadol in Male Rats

Abstract

Background: Repeated and long treatment with tramadol that could cause toxic metabolites by accumulation
in the body and with high level of risk of pharmokinetic interaction alongside the decreasing of tramadol,
therefore this study was carried out to investigate the toxic impact of the tramadol on the tissues of the brain
in the male rats.
Method: This experiment was accomplished and processed at environmental toxicology laboratory,
environmental studies department, institute of graduate studies and research, university of Alexandria, Alexandria
p) ovince, Egypt. a group of rats (32, male) from Albano waster subspecies and they weigh from 200-250g,
all belonging to the animal house of the faculty of medicine, university of Alexandria and grouping in to
four groups (8 rats for each group in each cage). In regards to the control group, they were given basal food
and tap water through-out 10 days by gastric tube, day by day. Group three the rats were fed with basal diet
and given Tramadol HCL orally in dose 45mg/ kg .B.W dissolved in (5ml) normal saline (0.9%) by gastric
tube, daily for Twenty days. Group for the rats were fed with basal diet and given Tramadol HCL orally in
dose 45mg/ kg .B.W dissolved in (5ml) normal saline (0.9%) by gastric tube, daily for Thirty days. When the
experimental period reached its end, kidney tissues of each rat were instantly removed and after that weighed then
put into 10 percent of neutral buffer formalin to be considered as a fixative solution.
The Results: The results showed significantly decrease in the heaviness of the brain in the groups of the
rats that given the Tramadol HCL in dose 45mg/ kg .B.W with increasing the time of administration as
compared to the control group. Histopathological changes were observed in rats brain tissues section the
rats that given Tramadol HCL orally in dose 45mg/ kg .B.W dissolved in (5ml) normal saline for ten days
revealed mild degree of tissue injury in the cerebral cortex, with few vacuolar degeneration and dilatation
of blood vessels, and the tissue sections of group two after ten days revealed mild degree of tissue injury in
the cerebral cortex, with few vacuolar degeneration and dilatation of blood vessels, while the three group
Observed increase in the vacuolar degeneration, with neural atrophy and degeneration of neurons with
reduction the neural process and pyknosis of the nuclei dilatation of blood vessels after twenty days of
tramadol administration. The tissue Sections the obtained from the group four after thirty days revealed
increase in the vacuolar degeneration, with more atrophy of the neural cells and complete reduction the
neural process and pyknosis of the nucleus in the injured neural cells and glyosis.
The Conclusion of this study there are harmful toxic effects when administrated the tramadol for long
period on the brain tissues, therefore abuse of tramadol should be avoided except with medical prescription
owing to its toxic effects.