Histopathological and Immunohistochemical Evaluation of Methotrexate-Induced Gonadal Damage in Rats: Role of SCF, mTOR, and SIRT-1
Objective: Methotrexate (MTX) is a highly effective chemotherapy for cancer. This drug has a gonadotoxic effect, mainly in the testes and ovaries. Our study used histopathological and immunohistochemical methods to assess the potential damage to testicular and ovarian tissue caused by MTX use. Metho...
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Galenos Publishing House
2024-12-01
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| Series: | Medeniyet Medical Journal |
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| author | Kübra Tuğçe KALKAN Betül YALÇIN Özge CENGİZ MAT Arzu Hanım YAY |
| author_facet | Kübra Tuğçe KALKAN Betül YALÇIN Özge CENGİZ MAT Arzu Hanım YAY |
| author_sort | Kübra Tuğçe KALKAN |
| collection | DOAJ |
| description | Objective: Methotrexate (MTX) is a highly effective chemotherapy for cancer. This drug has a gonadotoxic effect, mainly in the testes and ovaries. Our study used histopathological and immunohistochemical methods to assess the potential damage to testicular and ovarian tissue caused by MTX use.
Methods: Twenty-four Wistar albino rats, both male and female, were used in our study. Four sets of rats; control male, MTX male, control female, and MTX female were created. The male and female MTX-treated groups received a single intraperitoneal dose of 20 mg/kg MTX. The testes and ovaries of rats sacrificed under general anesthesia were extracted and histopathologically analyzed. In addition, the immunoreactivity intensities of stem cell factor (SCF), mechanistic target of rapamycin (mTOR), and SIRT-1 in both tissues were measured by immunohistochemistry.
Results: Johnsen's testicular biopsy score in the testicular seminiferous tubules was significantly lower in the MTX group than in the control group (p<0.001). The ovary showed substantial follicular degeneration (p<0.05), vascular congestion (p<0.01), and fibrosis (p<0.001). MTX reduced SCF immunoreactivity density in the testis and ovary (p<0.05). Furthermore, MTX reduced mTOR, a marker of autophagy, in the testis (p<0.05) and ovary (p<0.001) compared with the control. SIRT-1 intensity increased dramatically in the testis (p<0.001) and ovary (p<0.01) in the injured group, unlike the mTOR marker.
Conclusions: Our investigation revealed that the gonads incurred significant damage as a result of MTX. One vital option for reducing or eliminating this damage to the ovaries and testicles is the use of anti-oxidant-rich substances. |
| format | Article |
| id | doaj-art-e651b6233d05464e88f999e77767c596 |
| institution | Kabale University |
| issn | 2149-2042 2149-4606 |
| language | English |
| publishDate | 2024-12-01 |
| publisher | Galenos Publishing House |
| record_format | Article |
| series | Medeniyet Medical Journal |
| spelling | doaj-art-e651b6233d05464e88f999e77767c5962025-01-29T10:02:16ZengGalenos Publishing HouseMedeniyet Medical Journal2149-20422149-46062024-12-0139428329210.4274/MMJ.galenos.2024.04932MEDJ-04932Histopathological and Immunohistochemical Evaluation of Methotrexate-Induced Gonadal Damage in Rats: Role of SCF, mTOR, and SIRT-1Kübra Tuğçe KALKAN0Betül YALÇIN1Özge CENGİZ MAT2Arzu Hanım YAY3Kırşehir Ahi Evran University Faculty of Medicine, Department of Histology and Embriyology, Kırşehir, TürkiyeAdıyaman University Faculty of Medicine, Histology and Embriyology, Adıyaman, TürkiyeErciyes University Faculty of Medicine, Histology and Embriyology, Kayseri, TürkiyeErciyes University Faculty of Medicine, Histology and Embriyology, Kayseri, TürkiyeObjective: Methotrexate (MTX) is a highly effective chemotherapy for cancer. This drug has a gonadotoxic effect, mainly in the testes and ovaries. Our study used histopathological and immunohistochemical methods to assess the potential damage to testicular and ovarian tissue caused by MTX use. Methods: Twenty-four Wistar albino rats, both male and female, were used in our study. Four sets of rats; control male, MTX male, control female, and MTX female were created. The male and female MTX-treated groups received a single intraperitoneal dose of 20 mg/kg MTX. The testes and ovaries of rats sacrificed under general anesthesia were extracted and histopathologically analyzed. In addition, the immunoreactivity intensities of stem cell factor (SCF), mechanistic target of rapamycin (mTOR), and SIRT-1 in both tissues were measured by immunohistochemistry. Results: Johnsen's testicular biopsy score in the testicular seminiferous tubules was significantly lower in the MTX group than in the control group (p<0.001). The ovary showed substantial follicular degeneration (p<0.05), vascular congestion (p<0.01), and fibrosis (p<0.001). MTX reduced SCF immunoreactivity density in the testis and ovary (p<0.05). Furthermore, MTX reduced mTOR, a marker of autophagy, in the testis (p<0.05) and ovary (p<0.001) compared with the control. SIRT-1 intensity increased dramatically in the testis (p<0.001) and ovary (p<0.01) in the injured group, unlike the mTOR marker. Conclusions: Our investigation revealed that the gonads incurred significant damage as a result of MTX. One vital option for reducing or eliminating this damage to the ovaries and testicles is the use of anti-oxidant-rich substances.https://jag.journalagent.com/z4/download_fulltext.asp?pdir=medeniyet&un=MEDJ-04932methotrexatechemotherapytestisovary |
| spellingShingle | Kübra Tuğçe KALKAN Betül YALÇIN Özge CENGİZ MAT Arzu Hanım YAY Histopathological and Immunohistochemical Evaluation of Methotrexate-Induced Gonadal Damage in Rats: Role of SCF, mTOR, and SIRT-1 Medeniyet Medical Journal methotrexate chemotherapy testis ovary |
| title | Histopathological and Immunohistochemical Evaluation of Methotrexate-Induced Gonadal Damage in Rats: Role of SCF, mTOR, and SIRT-1 |
| title_full | Histopathological and Immunohistochemical Evaluation of Methotrexate-Induced Gonadal Damage in Rats: Role of SCF, mTOR, and SIRT-1 |
| title_fullStr | Histopathological and Immunohistochemical Evaluation of Methotrexate-Induced Gonadal Damage in Rats: Role of SCF, mTOR, and SIRT-1 |
| title_full_unstemmed | Histopathological and Immunohistochemical Evaluation of Methotrexate-Induced Gonadal Damage in Rats: Role of SCF, mTOR, and SIRT-1 |
| title_short | Histopathological and Immunohistochemical Evaluation of Methotrexate-Induced Gonadal Damage in Rats: Role of SCF, mTOR, and SIRT-1 |
| title_sort | histopathological and immunohistochemical evaluation of methotrexate induced gonadal damage in rats role of scf mtor and sirt 1 |
| topic | methotrexate chemotherapy testis ovary |
| url | https://jag.journalagent.com/z4/download_fulltext.asp?pdir=medeniyet&un=MEDJ-04932 |
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