Methadone and the Kidney: Dissecting Gender Differences in Inflammation and Oxidative Stress Responses

Document Type : Original Article

Authors

1 Student Research Committee, Afzalipour Faculty of Medicine, Kerman University of Medical Sciences, Kerman, Iran

2 Physiology Research Center, Institute of Neuropharmacology, Kerman University of Medical Sciences, Kerman, Iran

3 Cardiovascular Research Center, Institute of Basic and Clinical Physiology Sciences, Kerman University of Medical Sciences, Kerman, Iran

4 Medical Toxicology and Drug Abuse Research Center, (MTDRC), Department of Physiology, School of Medicine, Birjand University of Medical Sciences, Ghaffari Street, Birjand, Iran

5 Department of Pathology, Pathology and Stem Cell Research Center, Afzalipour Faculty of Medicine, Kerman University of Medical Sciences, Kerman, Iran

6 Physiology Research Center, Kerman University of Medical Sciences, Kerman, Iran

10.34172/ahj.1625

Abstract

Abstract
Background: This study explored the gender-specific effects of methadone, a synthetic opioid receptor agonist commonly used in opioid addiction treatment, on renal tissue and function. We aimed to elucidate the underlying mechanisms involving inflammatory pathways and redox system activity.
Methods: Forty-two Wistar rats (200-250 g) were allocated into six groups: three males and three females, each comprised of control, and methadone-treated 5 mg/kg and 20 mg/kg. Over eight weeks, animals received either saline or methadone syrup orally. Blood urea nitrogen (BUN) and serum creatinine (sCr) were measured in serum. The inflammatory cytokines and antioxidant enzyme activity were assessed in left kidneys, which were preserved at -80 °C, while histopathological analysis via H&E staining was done on the formalin-fixed right kidneys.
Findings: Methadone administration resulted in renal tissue injury characterized by enhanced glomerular and interstitial inflammation. Notable increases in malondialdehyde (MDA), BUN, sCr, transforming growth factor beta (TGF-β), tumor necrosis factor alpha (TNF-α), and interleukin 17 (IL-17) were observed in methadone-treated groups, indicating impaired renal function associated with oxidative stress and inflammation, with male rats exhibiting more severe alterations. Conversely, methadone treatment elevated glutathione peroxidase (GPx), and catalase (Cat) activities, predominantly in females.
Conclusion: Prolonged methadone therapy exerts a nephrotoxic effect through the activation of oxidative stress and inflammatory pathways, with male rats displaying greater renal pathology and dysfunction, potentially attributed to diminished antioxidant defenses.

Keywords

References

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Addiction & Health
Volume 17
Pages 1-8

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