APREPITANT AMELIORATES CYCLOPHOSPHAMIDE-INDUCED TESTICULAR TOXICITY IN MICE VIA SUPPRESSION OF P38 MITOGEN-ACTIVATED PROTEIN KINASE

Suzan Awad AbdelGhany Morsy, Department of Clinical Pharmacology, Faculty of Medicine, Alexandria University, Dr. Fahmi Abdelmeguid St., Mowassah campus, Alexandria 21561, EgyptFollow
Amira H. Eltrawy, Department of Human Anatomy and Embryology, Faculty of Medicine, Alexandria University, Dr. Fahmi Abdelmeguid St., Mowassah campus, Alexandria 21561, Egypt
Nehal Adel Khalil, Department of Medical Biochemistry, Faculty of Medicine, Alexandria University, Dr. Fahmi Abdelmeguid St., Mowassah campus, Alexandria 21561, Egypt
Abd ElAziz MM, Department of Pathology, Faculty of Medicine, Alexandria University, Dr. Fahmi Abdelmeguid St., Mowassah campus, Alexandria 21561, Egypt
Nourhan Mohamed Mohamed Saeed, Department of Forensic Medicine and Clinical Toxicology, Faculty of Medicine, Alexandria University
Gehad M. Khamis, Department of Clinical Pharmacology, Faculty of Medicine, Alexandria University, Dr. Fahmi Abdelmeguid St., Mowassah campus, Alexandria 21561, Egypt

Subject Area

Pharmacology

Article Type

Original Study

Abstract

Background: While cyclophosphamide (CP) is a commonly used immunosuppressant and anticancer drug, it has a high risk of testicular toxicity. The current study evaluated the protective and therapeutic actions of aprepitant (APR), a neurokinin-1 receptor blocker, against CP-induced testicular toxicity in mice and the role of oxidative stress and phosphorylated P38 mitogen-activated protein kinase (p-P38 MAPK) in this action.Methods: Forty male mice were assigned to four groups: control (vehicle only), CP-induced testicular toxicity (single 200 mg/kg intraperitoneal CP dose), APRprotected (20 mg/kg/day APR starting one day before CP, continued for 30 days), and APR-treated (same APR dose starting one hour after CP). Animals were sacrificed; testes were excised for sperm evaluation, histological examination of haematoxylin and eosin-stained sections, and biochemical analysis of malondialdehyde, reduced glutathione, and p-P38 MAPK levels.Results: APR improved sperm count, increased the percentage of active sperm, decreased dead sperm, and conserved testicular tissue architecture, according to histological analysis, in comparison to the CP-induced testicular toxicity-untreated group. It also raised the level of reduced glutathione while reducing malondialdehyde levels and p-P38 MAPK expression. Compared to the treated group, these improvements were more pronounced in the APR-preventive group.Conclusion: APR ameliorated the CP-induced testicular toxicity in mice by suppressing p-P38 MAPK and oxidative stress, preserving testicular tissue and spermatogenesis. Protective use of APR produced a more pronounced improvement

Recommended Citation

Morsy, Suzan Awad AbdelGhany; Eltrawy, Amira H.; Khalil, Nehal Adel; MM, Abd ElAziz; Saeed, Nourhan Mohamed Mohamed; and Khamis, Gehad M. (2025) "APREPITANT AMELIORATES CYCLOPHOSPHAMIDE-INDUCED TESTICULAR TOXICITY IN MICE VIA SUPPRESSION OF P38 MITOGEN-ACTIVATED PROTEIN KINASE," Mansoura Medical Journal: Vol. 54 : Iss. 4 , Article 8.
Available at: https://doi.org/10.58775/2735-3990.1460