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Molecular and hormonal changes caused by long-term use of high dose pregabalin on testicular tissue: the role of p38 MAPK, oxidative stress and apoptosis

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Abstract

In 1990, pregabalin was introduced as a novel antiepileptic drug that acts by binding selectively to the alpha-2-delta subunits of voltage-gated calcium channels resulting in increasing neuronal GABA levels and inhibiting the release of exciting neurotransmitters. The aim of our study is to assess the hazardous effects of prolonged high-dose pregabalin (like that abused by addicts) on testes and to clarify the potential causative mechanisms. The current study was conducted on 70 adult male Wistar albino rats which were divided into 7 groups. In our study we evaluated the effect of pregabalin, at concentrations 150 and 300 mg/kg/day for 90 days, on hormones; FSH, LH, testosterone and prolactin secretion. Our study also evaluated the expression of apoptosis-related genes BAX and BCL2 in testicular tissue in addition to the western blotted analysis of p38 Mitogen activated protein kinases (p38 MAPK). The levels of reduced glutathione, malondialdehyde and superoxide dismutase were also measured. Pregabalin decreased testosterone level while FSH, LH and prolactin showed a significant increase. It also produced genotoxicity through reversal of the BAX/BCL2 ratio; increased p38 MAPK level and induction of oxidative stress markers. The concomitant administration of vitamin E significantly reduced all the previously mentioned biochemical and hormonal adverse effects caused by pregabalin. Pregabalin can adversely affect male fertility particularly in addicts and patients who are being treated with it for long periods as those suffering from neuropathies and seizures. Antioxidants like vitamin E could have a role in amelioration.

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Authors and Affiliations

  1. Department of Forensic Medicine & Clinical Toxicology, Faculty of Medicine, Cairo University, Cairo, Egypt

    Sarah Hamed N. Taha, Hala Saied Zaghloul, Abla Abd El Rahman Ali & Iman Fawzy Gaballah

  2. Department of Medical Biochemistry & Molecular Biology, Faculty of Medicine, Cairo University, Cairo, Egypt

    Laila Ahmed Rashed

  3. Department of Pathology, Faculty of Medicine, Cairo University, Cairo, Egypt

    Rania Mohamed Sabry

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  1. Sarah Hamed N. Taha
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  2. Hala Saied Zaghloul
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  3. Abla Abd El Rahman Ali
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Contributions

SHT: Conceptualization, Methodology, Writing-Original draft preparation. HSZ: Supervision, Conceptualization. AAA: Supervision, Visualization. LAR: Supervision, Methodology, Investigation, Validation. RMS: Validation. IFG: Writing- Reviewing and Editing.

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Correspondence to Sarah Hamed N. Taha.

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The study complies with the Guide for the Care and Use of Laboratory Animals published by the National Institutes of Health (NIH Publications No. 8023, revised 1978) and is approved by the Ethical Committee, Faculty of Medicine, Cairo University and Cairo University Institutional Animal Care and Use Committee (CU-IACUC).

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Taha, S.H.N., Zaghloul, H.S., Ali, A.A.E. et al. Molecular and hormonal changes caused by long-term use of high dose pregabalin on testicular tissue: the role of p38 MAPK, oxidative stress and apoptosis. Mol Biol Rep 47, 8523–8533 (2020). https://doi.org/10.1007/s11033-020-05894-6

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