The Relationship Between Tramadol-Induced Oxidative Testis Injury and Reproductive Function Disorder and Adenosine Triphosphate

Tramadol, a central analgesic drug, is used to treat moderate to severe pain but can cause reproductive disorders. The pathogenesis of tramadol-induced reproductive damage may involve increased oxidative stress, pro-inflammatory cytokines, ATP depletion, and reduced antioxidant levels. In this study...

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Main Authors: Fevzi Bedir, Hüseyin Kocatürk, Mehmet Sefa Altay, Renad Mammadov, Bahadır Süleyman, Taha Abdulkadir Coban, Gülce Naz Yazici, Seval Bulut, Halis Süleyman
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Language:English
Published: MDPI AG 2025-07-01
Series:Life
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Online Access:https://www.mdpi.com/2075-1729/15/7/1078
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author Fevzi Bedir
Hüseyin Kocatürk
Mehmet Sefa Altay
Renad Mammadov
Bahadır Süleyman
Taha Abdulkadir Coban
Gülce Naz Yazici
Seval Bulut
Halis Süleyman
author_facet Fevzi Bedir
Hüseyin Kocatürk
Mehmet Sefa Altay
Renad Mammadov
Bahadır Süleyman
Taha Abdulkadir Coban
Gülce Naz Yazici
Seval Bulut
Halis Süleyman
author_sort Fevzi Bedir
collection DOAJ
description Tramadol, a central analgesic drug, is used to treat moderate to severe pain but can cause reproductive disorders. The pathogenesis of tramadol-induced reproductive damage may involve increased oxidative stress, pro-inflammatory cytokines, ATP depletion, and reduced antioxidant levels. In this study, subjects were divided into four groups: healthy control (HC), tramadol only (TM), ATP only (ATP), and ATP + tramadol (ATM). ATP was administered intraperitoneally at 4 mg/kg, and tramadol was administered orally at 50 mg/kg. Distilled water was given to the HC group. This regimen was repeated for three weeks. At the end of the treatment, testicular tissues from six rats in each group were analyzed biochemically and histopathologically after euthanasia. The remaining rats’ reproductive functions were evaluated. Long-term tramadol exposure resulted in oxidative stress, inflammation in testicular tissue, and reduced male reproductive capacity. Thinning of seminiferous tubule walls and thickening of basement membrane, irregularity in germ cells, increase in interstitial connective tissue, congestion in vessels, increase in Leyding cells and hyperplasia were found in the TM group. ATP treatment significantly reduced tramadol-induced increases in oxidants and pro-inflammatory cytokines, reversed the decline in antioxidants, and mitigated infertility in testicular tissue. Furthermore, ATP preserved the morphology of the testicular tissue. These findings suggest that ATP may offer therapeutic potential for tramadol-induced infertility.
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spelling doaj-art-343782cff9ef4804b3bfdb7bc7144cc02025-08-20T03:36:21ZengMDPI AGLife2075-17292025-07-01157107810.3390/life15071078The Relationship Between Tramadol-Induced Oxidative Testis Injury and Reproductive Function Disorder and Adenosine TriphosphateFevzi Bedir0Hüseyin Kocatürk1Mehmet Sefa Altay2Renad Mammadov3Bahadır Süleyman4Taha Abdulkadir Coban5Gülce Naz Yazici6Seval Bulut7Halis Süleyman8Department of Urology, Health Sciences University, Erzurum Regional Training and Research Hospital, Erzurum 25070, TurkeyDepartment of Urology, Health Sciences University, Erzurum Regional Training and Research Hospital, Erzurum 25070, TurkeyDepartment of Urology, Health Sciences University, Erzurum Regional Training and Research Hospital, Erzurum 25070, TurkeyDepartment of Pharmacology, Faculty of Medicine, Erzincan Binali Yildirim University, Erzincan 24100, TurkeyDepartment of Pharmacology, Faculty of Medicine, Erzincan Binali Yildirim University, Erzincan 24100, TurkeyDepartment of Biochemistry, Faculty of Medicine, Erzincan Binali Yildirim University, Erzincan 24100, TurkeyDepartment of Histology and Embryology, School of Medicine, Erzincan Binali Yildirim University, Erzincan 24100, TurkeyDepartment of Pharmacology, Faculty of Medicine, Erzincan Binali Yildirim University, Erzincan 24100, TurkeyDepartment of Pharmacology, Faculty of Medicine, Erzincan Binali Yildirim University, Erzincan 24100, TurkeyTramadol, a central analgesic drug, is used to treat moderate to severe pain but can cause reproductive disorders. The pathogenesis of tramadol-induced reproductive damage may involve increased oxidative stress, pro-inflammatory cytokines, ATP depletion, and reduced antioxidant levels. In this study, subjects were divided into four groups: healthy control (HC), tramadol only (TM), ATP only (ATP), and ATP + tramadol (ATM). ATP was administered intraperitoneally at 4 mg/kg, and tramadol was administered orally at 50 mg/kg. Distilled water was given to the HC group. This regimen was repeated for three weeks. At the end of the treatment, testicular tissues from six rats in each group were analyzed biochemically and histopathologically after euthanasia. The remaining rats’ reproductive functions were evaluated. Long-term tramadol exposure resulted in oxidative stress, inflammation in testicular tissue, and reduced male reproductive capacity. Thinning of seminiferous tubule walls and thickening of basement membrane, irregularity in germ cells, increase in interstitial connective tissue, congestion in vessels, increase in Leyding cells and hyperplasia were found in the TM group. ATP treatment significantly reduced tramadol-induced increases in oxidants and pro-inflammatory cytokines, reversed the decline in antioxidants, and mitigated infertility in testicular tissue. Furthermore, ATP preserved the morphology of the testicular tissue. These findings suggest that ATP may offer therapeutic potential for tramadol-induced infertility.https://www.mdpi.com/2075-1729/15/7/1078antioxidantATPinfertilitypro-inflammatoryrattramadol
spellingShingle Fevzi Bedir
Hüseyin Kocatürk
Mehmet Sefa Altay
Renad Mammadov
Bahadır Süleyman
Taha Abdulkadir Coban
Gülce Naz Yazici
Seval Bulut
Halis Süleyman
The Relationship Between Tramadol-Induced Oxidative Testis Injury and Reproductive Function Disorder and Adenosine Triphosphate
Life
antioxidant
ATP
infertility
pro-inflammatory
rat
tramadol
title The Relationship Between Tramadol-Induced Oxidative Testis Injury and Reproductive Function Disorder and Adenosine Triphosphate
title_full The Relationship Between Tramadol-Induced Oxidative Testis Injury and Reproductive Function Disorder and Adenosine Triphosphate
title_fullStr The Relationship Between Tramadol-Induced Oxidative Testis Injury and Reproductive Function Disorder and Adenosine Triphosphate
title_full_unstemmed The Relationship Between Tramadol-Induced Oxidative Testis Injury and Reproductive Function Disorder and Adenosine Triphosphate
title_short The Relationship Between Tramadol-Induced Oxidative Testis Injury and Reproductive Function Disorder and Adenosine Triphosphate
title_sort relationship between tramadol induced oxidative testis injury and reproductive function disorder and adenosine triphosphate
topic antioxidant
ATP
infertility
pro-inflammatory
rat
tramadol
url https://www.mdpi.com/2075-1729/15/7/1078
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