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Fenofibrate ameliorates testicular damage in rats with streptozotocin-induced type 1 diabetes: role of HO-1 and p38 MAPK

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Abstract

Background

Since diabetes mellitus type-1 (DM-1) induces testicular oxidative and inflammatory damage with finally an ultimate male infertility, and as fenofibrate (FEN) plays an important antioxidant and anti-inflammatory role, the aim of the present study was to investigate the effects of FEN on diabetes-induced reproductive damage and clarifying the underlying related mechanisms.

Methods

DM-1 was induced in male Wistar rats by a single intraperitoneal injection of streptozotocin (50 mg/kg). FEN (100 mg/kg/day, orally) was administrated to diabetic rats for 4 weeks. Testicular damage was detected by estimation of both testicular and body weights, assessment of serum testosterone, testicular oxidative stress parameters (malondialdehyde and nitric oxide levels) and testicular oxidant defenses (reduced glutathione, superoxide dismutase and hemeoxygenase-1). Expressions of the inflammatory markers (inducible nitric oxide synthase, p38 mitogen-activated protein kinase (MAPK), tumor necrosis factor alpha, interleukin-6 and apoptotic marker (caspase-3) were evaluated in testicular tissue. Our results were confirmed by histopathological examination of testicular tissues.

Results

Diabetic testicular damage was proved by both biochemical and histopathological examinations. FEN treatment reversed diabetic testicular damage; normalized the serum testosterone level, improved anti-oxidative capacity, ameliorated the pro-inflammatory cytokine expression in testicular tissue with the down regulation of p38 MAPK mediated-testicular apoptosis.

Conclusion

FEN treatment exerted a protective effect against streptozotocin-induced diabetic reproductive dysfunction not only through its powerful antioxidant and hypoglycemic effects, but also through its anti-inflammatory and anti-apoptotic effect via down-regulation of testicular p38 MAPK expression in diabetic rats.

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This research did not receive any specific Grant from funding agencies in the public, commercial or not-for-profit sectors.

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Authors and Affiliations

  1. Department of Pharmacology, Faculty of Medicine, Minia University, Minia, 61511, Egypt

    Asmaa Mohamed Abdel-Aziz & Hanaa Mohamed Khalaf

  2. Department of Anatomy, Faculty of Medicine, Minia University, Minia, 61511, Egypt

    Samah Mohammed Mahmoud Abozaid

  3. Department of Pathology, Faculty of Medicine, Minia University, Minia, 61511, Egypt

    Rehab Kamal Mohammed Yousef

  4. Department of Biochemistry, Faculty of Medicine, Minia University, Minia, 61511, Egypt

    Mostafa Mourad Mohammed

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  1. Asmaa Mohamed Abdel-Aziz
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  2. Samah Mohammed Mahmoud Abozaid
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Correspondence to Hanaa Mohamed Khalaf.

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Abdel-Aziz, A.M., Abozaid, S.M.M., Yousef, R.K.M. et al. Fenofibrate ameliorates testicular damage in rats with streptozotocin-induced type 1 diabetes: role of HO-1 and p38 MAPK. Pharmacol. Rep 72, 1645–1656 (2020). https://doi.org/10.1007/s43440-020-00096-0

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  • DOI: https://doi.org/10.1007/s43440-020-00096-0

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