Hesperidin Mitigates Cyclophosphamide-Induced Testicular Dysfunction via Altering the Hypothalamic Pituitary Gonadal Axis and Testicular Steroidogenesis, Inflammation, and Apoptosis in Male Rats
Cyclophosphamide (CP) is a cytotoxic, cell cycle, non-specific, and antiproliferative drug. This study aimed to address the toxic effects of CP on male fertility and the possible ameliorative role of hesperidin (HSP). Thirty-two adult albino rats were randomly divided into four groups, namely, the n...
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MDPI AG
2023-02-01
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| Online Access: | https://www.mdpi.com/1424-8247/16/2/301 |
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| author | Tarek Khamis Abdelmonem Awad Hegazy Samaa Salah Abd El-Fatah Eman Ramadan Abdelfattah Marwa Mohamed Mahmoud Abdelfattah Liana Mihaela Fericean Ahmed Hamed Arisha |
| author_facet | Tarek Khamis Abdelmonem Awad Hegazy Samaa Salah Abd El-Fatah Eman Ramadan Abdelfattah Marwa Mohamed Mahmoud Abdelfattah Liana Mihaela Fericean Ahmed Hamed Arisha |
| author_sort | Tarek Khamis |
| collection | DOAJ |
| description | Cyclophosphamide (CP) is a cytotoxic, cell cycle, non-specific, and antiproliferative drug. This study aimed to address the toxic effects of CP on male fertility and the possible ameliorative role of hesperidin (HSP). Thirty-two adult albino rats were randomly divided into four groups, namely, the negative control, HSP, CP-treated, and CP+HSP-treated groups. The CP-treated rats showed a significant reduction in the levels of serum LH, FSH, testosterone, prolactin, testicular glutathione peroxidase (GPx), and total antioxidant capacity (TAC) with an elevation in levels of malondialdehyde (MDA), and p53, and iNOS immune expression, compared to the control group. A significant downregulation in hypothalamic KISS-1, KISS-1r, and GnRH, hypophyseal GnRHr, and testicular mRNA expression of steroidogenesis enzymes, PGC-1α, PPAR-1, IL10, and GLP-1, as well as a significant upregulation in testicular mRNA of P53 and IL1β mRNA expression, were detected in the CP-treated group in comparison to that in the control group. The administration of HSP in CP-treated rats significantly improved the levels of serum LH, FSH, testosterone, prolactin, testicular GPx, and TAC, with a reduction in levels of MDA, and p53, and iNOS immune expression compared to the CP-treated group. A significant upregulation in hypophyseal GnRHr, and testicular mRNA expression of CYP19A1 enzymes, PPAR-1, IL10, and GLP-1, as well as a significant downregulation in testicular mRNA of P53 and IL1β mRNA expression, were detected in the CP+HSP-treated group in comparison to that in the CP-treated group. In conclusion, HSP could be a potential auxiliary agent for protection from the development of male infertility. |
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| issn | 1424-8247 |
| language | English |
| last_indexed | 2024-03-11T08:18:24Z |
| publishDate | 2023-02-01 |
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| spelling | doaj.art-e484a8ce3afe41089700b77796e6d30a2023-11-16T22:37:45ZengMDPI AGPharmaceuticals1424-82472023-02-0116230110.3390/ph16020301Hesperidin Mitigates Cyclophosphamide-Induced Testicular Dysfunction via Altering the Hypothalamic Pituitary Gonadal Axis and Testicular Steroidogenesis, Inflammation, and Apoptosis in Male RatsTarek Khamis0Abdelmonem Awad Hegazy1Samaa Salah Abd El-Fatah2Eman Ramadan Abdelfattah3Marwa Mohamed Mahmoud Abdelfattah4Liana Mihaela Fericean5Ahmed Hamed Arisha6Department of Pharmacology and Laboratory of Biotechnology, Faculty of Veterinary Medicine, Zagazig University, Zagazig 44519, EgyptAnatomy and Embryology, Faculty of Dentistry, Zarqa University, Zarqa 13110, JordanHuman Anatomy & Embryology Department, Faculty of Medicine, Zagazig University, Zagazig 44519, EgyptHuman Anatomy & Embryology Department, Faculty of Medicine, Zagazig University, Zagazig 44519, EgyptHuman Anatomy & Embryology Department, Faculty of Medicine, Zagazig University, Zagazig 44519, EgyptBiology Department, Faculty of Agriculture, University of Life Sciences “King Michael I of Romania” from Timisoara, Aradului St. 119, 300645 Timisoara, RomaniaDepartment of Animal Physiology and Biochemistry, Faculty of Veterinary Medicine, Badr University in Cairo, Badr City 11829, EgyptCyclophosphamide (CP) is a cytotoxic, cell cycle, non-specific, and antiproliferative drug. This study aimed to address the toxic effects of CP on male fertility and the possible ameliorative role of hesperidin (HSP). Thirty-two adult albino rats were randomly divided into four groups, namely, the negative control, HSP, CP-treated, and CP+HSP-treated groups. The CP-treated rats showed a significant reduction in the levels of serum LH, FSH, testosterone, prolactin, testicular glutathione peroxidase (GPx), and total antioxidant capacity (TAC) with an elevation in levels of malondialdehyde (MDA), and p53, and iNOS immune expression, compared to the control group. A significant downregulation in hypothalamic KISS-1, KISS-1r, and GnRH, hypophyseal GnRHr, and testicular mRNA expression of steroidogenesis enzymes, PGC-1α, PPAR-1, IL10, and GLP-1, as well as a significant upregulation in testicular mRNA of P53 and IL1β mRNA expression, were detected in the CP-treated group in comparison to that in the control group. The administration of HSP in CP-treated rats significantly improved the levels of serum LH, FSH, testosterone, prolactin, testicular GPx, and TAC, with a reduction in levels of MDA, and p53, and iNOS immune expression compared to the CP-treated group. A significant upregulation in hypophyseal GnRHr, and testicular mRNA expression of CYP19A1 enzymes, PPAR-1, IL10, and GLP-1, as well as a significant downregulation in testicular mRNA of P53 and IL1β mRNA expression, were detected in the CP+HSP-treated group in comparison to that in the CP-treated group. In conclusion, HSP could be a potential auxiliary agent for protection from the development of male infertility.https://www.mdpi.com/1424-8247/16/2/301cyclophosphamidehesperidinapoptosisP53iNOSoxidative stress |
| spellingShingle | Tarek Khamis Abdelmonem Awad Hegazy Samaa Salah Abd El-Fatah Eman Ramadan Abdelfattah Marwa Mohamed Mahmoud Abdelfattah Liana Mihaela Fericean Ahmed Hamed Arisha Hesperidin Mitigates Cyclophosphamide-Induced Testicular Dysfunction via Altering the Hypothalamic Pituitary Gonadal Axis and Testicular Steroidogenesis, Inflammation, and Apoptosis in Male Rats Pharmaceuticals cyclophosphamide hesperidin apoptosis P53 iNOS oxidative stress |
| title | Hesperidin Mitigates Cyclophosphamide-Induced Testicular Dysfunction via Altering the Hypothalamic Pituitary Gonadal Axis and Testicular Steroidogenesis, Inflammation, and Apoptosis in Male Rats |
| title_full | Hesperidin Mitigates Cyclophosphamide-Induced Testicular Dysfunction via Altering the Hypothalamic Pituitary Gonadal Axis and Testicular Steroidogenesis, Inflammation, and Apoptosis in Male Rats |
| title_fullStr | Hesperidin Mitigates Cyclophosphamide-Induced Testicular Dysfunction via Altering the Hypothalamic Pituitary Gonadal Axis and Testicular Steroidogenesis, Inflammation, and Apoptosis in Male Rats |
| title_full_unstemmed | Hesperidin Mitigates Cyclophosphamide-Induced Testicular Dysfunction via Altering the Hypothalamic Pituitary Gonadal Axis and Testicular Steroidogenesis, Inflammation, and Apoptosis in Male Rats |
| title_short | Hesperidin Mitigates Cyclophosphamide-Induced Testicular Dysfunction via Altering the Hypothalamic Pituitary Gonadal Axis and Testicular Steroidogenesis, Inflammation, and Apoptosis in Male Rats |
| title_sort | hesperidin mitigates cyclophosphamide induced testicular dysfunction via altering the hypothalamic pituitary gonadal axis and testicular steroidogenesis inflammation and apoptosis in male rats |
| topic | cyclophosphamide hesperidin apoptosis P53 iNOS oxidative stress |
| url | https://www.mdpi.com/1424-8247/16/2/301 |
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