A short-term comparison between the effect of two different concentrations of methotrexate on ovarian tissues and function of female albino rats

Authors

  • Alak Hussein college of medicine
  • Samara M. Ali dept. of pharmacology, college of medicine , university of Baghdad

DOI:

https://doi.org/10.32007/jfacmedbagdad.6441967

Abstract

Background: methotrexate is an antifolate that is widely used in cancers and inflammatory or auto- immune diseases, it is also known to be contraindicated in pregnancy, breast feeding and not recommended in patients planning to be parents since it has a harmful effect on fetus and gonads.Ovarian function can be evaluated by certain parameters like the levels of female hormones or anti- Mullerian hormone which is considered as a good indicator for this purpose or histopathological examination of ovarian follicles especially the primordial follicles.

  Objective: the aim of this study is to determine the effect of two different concentrations of methotrexate on ovarian tissue integrity and function.

  Materials and method: adult female albino rats (n=30) were randomly divided in to 3 groups; group A (n=10) in which animals were treated with i. p injection of normal saline once weekly for four weeks, group B (n=10) in which animals were treated with i. p. injection of 1mg/ kg bw of methotrexate once weekly for four weeks, and lastly group C in which animals were treated with i. p. injection of 2.5 mg/ kg bw of methotrexate once weekly for four weeks. Then serum level of anti- Mullerian hormone were measured and histopathological examination of the ovaries were done to evaluate ovarian injury caused by methotrexate treatment.

Results: this study has demonstrated that methotrexate in the both 1mg and 2.5 mg / kg of BW doses did not significantly reduce the levels of anti- Mullerian hormone and the number of primordial follicles and atretic follicles were also not significantly affected by the treatment of methotrexate in both doses. While histopathological examination revealed mild ovarian damage in case of treatment with 1mg/ kg bw of methotrexate and moderate damage in case of treatment with 2.5 mg/ kg bw of methotrexate.

 Conclusions: there is no important difference between the effects of 1 and 2.5 mg/ kg of BW of methotrexate on ovarian function but there is a slight difference in the effects of the two different doses on the integrity of ovarian tissue.

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References

- Bedoschi G, Navarro PA, Oktay K. Chemotherapy-induced damage to ovary: mechanisms and clinical impact. Future oncology. 2016 Oct;12(19):2333-44.

- Shohda AA, El-banna A, Abdel Fattah F. The possible protective effect of folic acid against methotrexate induced ovarian damage in female albino rats.«Light and electron microscopic study. Bulletin of the National Nutrition Institute of the Arab Republic of Egypt. 2017 Nov 1;49(1):1-24.

‏3- Hannoodee M, Mittal M. Methotrexate. InStatPearls [Internet] 2021 Mar 7. StatPearls Publishing.

- Bedoui Y, Guillot X, Sélambarom J, Guiraud P, Giry C, Jaffar-Bandjee MC, Ralandison S, Gasque P. Methotrexate an old drug with new tricks. International journal of molecular sciences. 2019 Oct 10;20(20):5023.

- TÜRKLER C, Onat T, Yildirim E, Kaplan S, YAZICI G, Mammadov R, Sunar M. An experimental study on the use of lycopene to prevent infertility due to acute oxidative ovarian damage caused by a single high dose of methotrexate. Advances in Clinical and Experimental Medicine. 2020;29(1).

- Silva EG, Kim G, Bakkar R, Bozdag Z, Shaye-Brown A, Loghavi S, Stolnicu S, Hadareanu V, Bulgaru D, Cayax LI, Pitalua MC. Histology of the normal ovary in premenopausal patients. Annals of Diagnostic Pathology. 2020 Jun 1;46:151475.

- Kinnear HM, Tomaszewski CE, Chang FL, Moravek MB, Xu M, Padmanabhan V, Shikanov A. The ovarian stroma as a new frontier. Reproduction. 2020 Sep 1;160(3):R25-39.

- Moolhuijsen LM, Visser JA. Anti-Müllerian hormone and ovarian reserve: update on assessing ovarian function. The Journal of Clinical Endocrinology & Metabolism. 2020 Nov 1;105(11):3361-73.

- Soylu Karapinar O, Pinar N, Özcan O, Özgür T, Dolapçıoğlu K. Protective effect of alpha-lipoic acid in methotrexate-induced ovarian oxidative injury and decreased ovarian reserve in rats. Gynecological Endocrinology. 2017 Aug 3;33(8):653-9.

- Daniel WW, Cross CL. Biostatistics: a foundation for analysis in the health sciences. Wiley; 2018 Nov 13.

- Kalaiselvi VS, Saikumar P, Prabhu K. The anti mullerian hormone-a novel marker for assessing the ovarian reserve in women with regular menstrual cycles. Journal of clinical and diagnostic research: JCDR. 2012 Dec;6(10):1636.

- Sahin C, Taylan E, Akdemir A, Ozgurel B, Taskıran D, Ergenoglu AM. The impact of salpingectomy and single-dose systemic methotrexate treatments on ovarian reserve in ectopic pregnancy. European Journal of Obstetrics & Gynecology and Reproductive Biology. 2016 Oct 1;205:150-2.

- Brouwer J, Laven JS, Hazes JM, Schipper I, Dolhain RJ. Levels of serum anti–Müllerian hormone, a marker for ovarian reserve, in women with rheumatoid arthritis. Arthritis care & research. 2013 Sep;65(9):1534-8.

- Benian A, Guralp O, Uzun DD, Okyar A, Sahmay S. The effect of repeated administration of methotrexate (MTX) on rat ovary: measurement of serum antimullerian hormone (AMH) levels. Gynecological Endocrinology. 2013 Mar 1;29(3):226-9.

- Shirazi M, Pooransari P, Hajiha N, Shaker Z, Ghazi M, Tanha FD, Yekta BG, Ghaemi M. Effect of single-dose methotrexate treatment on ovarian reserve in women with ectopic pregnancy undergoing infertility treatment: a single-center experience. International Journal of Fertility & Sterility. 2020 Apr;14(1):23.

- Sarma UC, Winship AL, Hutt KJ. Comparison of methods for quantifying primordial follicles in the mouse ovary. Journal of Ovarian Research. 2020 Dec;13(1):1-1.

- Ulug P, Oner G. Evaluation of the effects of single or multiple dose methotrexate administration, salpingectomy on ovarian reserve of rat with the measurement of anti-Müllerian hormone (AMH) levels and histological analysis. European Journal of Obstetrics & Gynecology and Reproductive Biology. 2014 Oct 1;181:205-9.

- Anğın AD, Çöğendez E, Gün İ, Sakin Ö, Çıkman MS, Başak K, Kaptanağası AO, Alan Y, Alan M, Beyan E. The Effect of Dehydroepiandrosterone on Ovarian Reserve in Ovarian Damage Caused by Methotrexate. Medical Laboratory Technology Journal. 2020 May 22;6(1).

- Kyaw MT, Sakthiswary R, Amelia ZA, Rahana AR, Munirah MM. Effects of Methotrexate Therapy on the Levels of Gonadotropic Hormones in Rheumatoid Arthritis Patients of Reproductive Age. Cureus. 2020 Apr 11;12(4).

- Fu J, Liu Y, Wang C, Zhang H, Yu B, Wang Y, Zhu H. Persistent follicular granulosa cell senescence and apoptosis induced by methotrexate leading to oocyte dysfunction and aberrant embryo development. Clinical and translational science. 2021 Sep;14(5):2043-54.

- AlBasher G, AlKahtane AA, Saud Alarifi DA, Alessia MS, Almeer RS, Abdel-Daim MM, Al-Sultan NK, Al-Qahtani AA, Ali H, Alkahtani S. Methotrexate-induced apoptosis in human ovarian adenocarcinoma SKOV-3 cells via ROS-mediated bax/bcl-2-cyt-c release cascading. OncoTargets and therapy. 2019;12:21.

- Jassim NA. Predictors of Response to (Etanercept) in the Treatment of Iraqi Patients with Active Rheumatoid Arthritis. Journal of the Faculty of Medicine Baghdad. 2015 Apr 5;57(1):35-9.

- Al-Taee HA. The Role of Antimullerian Hormone in the Diagnosis of Poly Cystic Ovarian Syndrom. JFacMedBagdad [Internet]. 2014 Jan. 2 [cited 2022 Sep. 1];55(4):373-8. Available from: https://iqjmc.uobaghdad.edu.iq/index.php/19JFacMedBaghdad36/article/view/589.

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Published

13.01.2023

How to Cite

1.
Hussein A, Ali SM. A short-term comparison between the effect of two different concentrations of methotrexate on ovarian tissues and function of female albino rats. J Fac Med Baghdad [Internet]. 2023 Jan. 13 [cited 2024 Dec. 22];64(4):280-5. Available from: https://iqjmc.uobaghdad.edu.iq/index.php/19JFacMedBaghdad36/article/view/1967

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