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Tramadol Promotes Oxidative Stress, Fibrosis, Apoptosis, Ultrastructural and Biochemical alterations in the Adrenal Cortex of Adult Male Rat with Possible Reversibility after Withdrawal

Published online by Cambridge University Press:  05 May 2020

Amany Mohamed Shalaby Open the ORCID record for Amany Mohamed Shalaby [Opens in a new window] ,
Adel Mohamed Aboregela ,
Mohamed Ali Alabiad  and
Dina Fouad El Shaer
Amany Mohamed Shalaby*
Affiliation:
Histology and Cell Biology Department, Faculty of Medicine, Tanta University, Tanta31527, Egypt
Adel Mohamed Aboregela
Affiliation:
Human Anatomy and Embryology Department, Faculty of Medicine, Zagazig University, Zagazig44519, Egypt Basic Medical Sciences Department, College of Medicine, Bisha University, Bisha, Kingdom of Saudi Arabia
Mohamed Ali Alabiad
Affiliation:
Pathology Department, Faculty of Medicine, Zagazig University, Zagazig44519, Egypt
Dina Fouad El Shaer
Affiliation:
Histology and Cell Biology Department, Faculty of Medicine, Tanta University, Tanta31527, Egypt
*
*Author for correspondence: Amany Mohamed Shalaby, E-mail: amany.shalaby@med.tanta.edu.eg
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Abstract

Tramadol is a centrally acting analgesic drug, used for the management of moderate to severe pain in a variety of diseases. The long-term use of tramadol can induce endocrinopathy. This study aimed to evaluate the effect of tramadol dependence on the adrenal cortex and the effect of its withdrawal. Thirty adult male rats were divided into three experimental groups: the control group, the tramadol-dependent group that received increasing therapeutic doses of tramadol orally for 1 month, and the recovery group that received tramadol in a dose and duration similar to the previous group followed by a withdrawal period for another month. Specimens from the adrenal cortex were processed for histological, immunohistochemical, enzyme assay, and quantitative real-time PCR (RT-qPCR) studies. Tramadol induced a significant increase in malondialdehyde level and a significant decrease in the levels of glutathione peroxidase and superoxide dismutase. A significant decrease in the levels of adrenocorticotrophic hormones, aldosterone, cortisol, corticosterone, and dehydroepiandrosterone sulfate was also detected. Severe histopathological changes in the adrenal cortex were demonstrated in the form of disturbed architecture, swollen cells, and shrunken cells with pyknotic nuclei. Inflammatory cellular infiltration and variable-sized homogenized areas were also detected. A significant increase in P53 and Bax immunoreaction was detected and confirmed by RT-qPCR. The ultrastructural examination showed irregular, shrunken adrenocorticocytes with dense nuclei. Dilated smooth endoplasmic reticulum, mitochondria with disrupted cristae, and numerous coalesced lipid droplets were also demonstrated. All these changes started to return to normal after the withdrawal of tramadol. Thus, it was confirmed that the long-term use of tramadol can induce severe adrenal changes with subsequent insufficiency.

Keywords

adrenal cortexelectron microscopyoxidative stressRT-qPCRtramadol
Type
Biological Applications
Information
Microscopy and Microanalysis , Volume 26 , Issue 3 , June 2020 , pp. 509 - 523
Copyright
Copyright © Microscopy Society of America 2020

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