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Fenofibrate and Diosmetin in a rat model of testicular toxicity: New insight on their protective mechanism through PPAR-α/NRF-2/HO-1 signaling pathway.

Authors
  • Alqahtani, Moneerah J1
  • Negm, Walaa A2
  • Saad, Hebatallah M3
  • Salem, Esraa A4
  • Hussein, Ismail A5
  • Ibrahim, Hanaa A6
  • 1 Department of Pharmacognosy, College of Pharmacy, King Saud University, P.O. Box 2457, Riyadh 11451, Saudi Arabia. Electronic address: [email protected]. , (Saudi Arabia)
  • 2 Department of Pharmacognosy, Faculty of Pharmacy, Tanta University, Tanta 31527, Egypt. Electronic address: [email protected]. , (Egypt)
  • 3 Department of Pathology, Faculty of veterinary medicine, Matrouh University, Marsa Matrouh, Egypt. Electronic address: [email protected]. , (Egypt)
  • 4 Department of Medical Physiology, Faculty of Medicine, Menoufia University, Shebeen ElKom 32511, Egypt. Electronic address: [email protected]. , (Egypt)
  • 5 Department of Pharmacognosy and Medicinal Plants, Faculty of Pharmacy (Boys), Al-Azhar University, Cairo 11884, Egypt. Electronic address: [email protected]. , (Egypt)
  • 6 Department of Pharmacology and Toxicology, Faculty of Pharmacy, University of Tanta, Egypt. Electronic address: [email protected]. , (Egypt)
Type
Published Article
Journal
Biomedicine & pharmacotherapy = Biomedecine & pharmacotherapie
Publication Date
Sep 01, 2023
Volume
165
Pages
115095–115095
Identifiers
DOI: 10.1016/j.biopha.2023.115095
PMID: 37413905
Source
Medline
Keywords
Language
English
License
Unknown

Abstract

One of the most significant chemotherapeutic side effects of cisplatin (Cis) that limits its use and efficacy is testicular toxicity. Thus, the objective of the present study was to investigate the possible ameliorative effect of Fenofibrate (Fen), Diosmetin (D), and their combination against cis-mediated testicular damage. Fifty-four adult male albino rats were randomly allocated into nine groups (6 rats each): Control group, Fen (100 mg/kg), D20 (20 mg/kg), D40 (40 mg/kg), Cis group (7 mg/kg), Cis +Fen group (7 mg/kg+100 mg/kg), Cis+D20 group (7 mg/kg+20 mg/kg), Cis+D40 group (7 mg/kg+40 mg/kg), Cis+Fen+D40 treated group (7 mg/kg+100 mg/kg+40 mg/kg). Relative testicular weight, epididymal sperm count and viability, serum testosterone level, testicular oxidative stress indices, mRNA expression of peroxisome proliferator-activated receptor alpha (PPAR-α), nuclear factor erythroid 2-related factor 2 (Nrf2) and heme oxygenase 1 (HO-1), histopathological, and immunohistochemical alterations were assessed. Our results revealed that cis administration induced testicular oxidative and inflammatory damage as indicated by a substantial reduction in relative testicular weight, sperm parameters, serum testosterone levels, the antioxidant enzyme activity of catalase, and Johnson's histopathological score, PPAR-α/NRF-2/HO-1 and proliferating cell nuclear antigen (PCNA) immunoexpression with marked increment in malondialdehyde (MDA), Cosentino's score, nuclear factor kappa B (NF-κβ p65), interleukin (IL)- 1β and caspase 3 in testicular tissue. Interestingly, Fen and D diminished the harmful effects of cis on testes via upregulation of the antioxidant activities and downregulation of lipid peroxidation, apoptosis, and inflammation. Moreover, the combination therapy Fen/D40 also exhibited a more pronounced enhancement of previous markers than either treatment alone. In conclusion, because of their antioxidant, anti-inflammatory, and anti-apoptotic properties, cotreatment with Fen or D or their combination could be beneficial in reducing the harmful impacts of cis on testicular tissue, particularly in patients that receive cis chemotherapy. Copyright © 2023 The Authors. Published by Elsevier Masson SAS.. All rights reserved.

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