Histopathological Changes in Brain Tissuesassociated Withoral Administration of Tramadol in Male Rats
Keywords:Tramadol HCL, Histopathological changes,Brain tissues
Background: Repeated and long treatment with tramadol might lead to accumulation of toxic metabolites in
the body and increase the risk for pharmacokinetic interaction and decrease the clearance of tramadol,therefore
this studywas performed to investigate the toxic impact of the tramadol on the tissues of the brain in the
Method: The experiment was carried out at Environmental Toxicology Laboratory, Department of Environmental
Studies, Institute of Graduate Studies and Research, Alexandria University, Alexandria, Egypt.Thirty-two Albano
Waster male rats weighing (200-250 g) were obtained from the animal house of the Faculty of Medicine,
Alexandria University, andgrouping into four groups (8 rats for each group in each cage). The Control group
was fed a basal diet and given tap water daily for ten days. In group two the rats were fed 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 Ten days. In 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. The group
for the rats was 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. At the end of the experimental period Kidney
tissues of each rat were immediately removed and after weighted put into 10% neutral buffer formalin as a
fixative solution and stained with Hematoxylin –Eosin stain.
The Results: The results observed a significant decrease in the weight of the brain in the groups of the
rats that were given the Tramadol HCL in dose 45mg/ kg .B.W with increasing the time of administration
as compared with 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 a mild degree of tissue injury in the cerebral cortex, with few vacuolar degeneration and
dilatation of blood vessels, and the tissue sections of grouptwoafter ten days revealed a mild degree of tissue
injury in the cerebral cortex, with few vacuolar degeneration and dilatation of blood vessels, whilethe three
groupsObserved 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 obtained from group four after thirty days revealed an increase
in the vacuolar degeneration, with more atrophy of the neural cells and complete reduction of the neural
process and pyknosis of the nucleus in the injured neural cells and gliosis.
The conclusion of this study there are harmful toxic effects when administrated tramadol for long period on
the brain tissues, therefore an abuse of tramadol should be avoided except with medical prescription owing
to its toxic effects.
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