Overview of the Evaluation of the Destructive Effect of Procarbazine on the Ovarian Reserve in the Apoptotic, Inflammatory, and Oxidative Pathways

Overview

Journal Arch Med Sci

Specialty General Medicine

Date 2025 Feb 19

PMID 39967960

Authors

Kezban Kartlasmis

Ayse Nur Cakir Gungor

Yurdun Kuyucu

Samet Kara

Affiliations

Soon will be listed here.

Abstract

The use of chemotherapeutic agents during childhood, adolescence, and early adulthood has a detrimental effect on ovarian functions, leading to a decrease in ovarian reserves, thus adversely affecting fertility. Alkylating agents are one of the most frequently used groups of chemotherapeutics in this age group. An important and effective chemotherapeutic drug, procarbazine is used to treat brain tumors and Hodgkin lymphoma in children, adolescents, and young adults. This agent is also an indispensable component of combination-type chemotherapy. Procarbazine has a detrimental impact on ovarian reserve by directly targeting the oocyte or indirectly through somatic cell destruction. Evidence gathered thus far indicates that procarbazine's mode of action in the ovaries may involve apoptosis, inflammation, and oxidative stress. This review seeks to clarify the processes by which procarbazine might induce apoptosis, inflammation, and oxidative stress, hence affecting ovarian reserve and functioning.

References

Spears N, Lopes F, Stefansdottir A, Rossi V, De Felici M, Anderson R . Ovarian damage from chemotherapy and current approaches to its protection. Hum Reprod Update. 2019; 25(6):673-693. PMC: 6847836. DOI: 10.1093/humupd/dmz027. View

Vining L, Zak L, Harvey S, Harvey K . The role of apoptosis in cryopreserved animal oocytes and embryos. Theriogenology. 2021; 173:93-101. DOI: 10.1016/j.theriogenology.2021.07.017. View

Cakir Gungor A, Gencer M, Karaca T, Hacivelioglu S, Uysal A, Korkmaz F . The effect of hesperetin on ischemia-reperfusion injury in rat ovary. Arch Gynecol Obstet. 2014; 290(4):763-9. DOI: 10.1007/s00404-014-3267-8. View

Zhang F, Kong L, Zhao A, Ge W, Yan Z, Li L . Inflammatory cytokines as key players of apoptosis induced by environmental estrogens in the ovary. Environ Res. 2021; 198:111225. DOI: 10.1016/j.envres.2021.111225. View

Roness H, Kashi O, Meirow D . Prevention of chemotherapy-induced ovarian damage. Fertil Steril. 2015; 105(1):20-9. DOI: 10.1016/j.fertnstert.2015.11.043. View

Ferro R, Pais A, Sousa A, Almeida Santos T . Fertility preservation in women with haematological malignancies. Hum Fertil (Camb). 2022; 26(5):998-1007. DOI: 10.1080/14647273.2022.2042605. View

Turkler C, Kiremitli T, Onat T, Yildirim E, Yazici G, Mammadov R . Can pycnogenol prevent cisplatin-induced damage in uterus and ovaries?. Arch Med Sci. 2022; 18(5):1364-1371. PMC: 9479720. DOI: 10.5114/aoms.2019.90414. View

Mohammadi M . Oxidative Stress and Polycystic Ovary Syndrome: A Brief Review. Int J Prev Med. 2019; 10:86. PMC: 6547785. DOI: 10.4103/ijpvm.IJPVM_576_17. View

Timoteo-Ferreira F, Abreu D, Mendes S, Matos L, Rodrigues A, Almeida H . Redox imbalance in age-related ovarian dysfunction and perspectives for its prevention. Ageing Res Rev. 2021; 68:101345. DOI: 10.1016/j.arr.2021.101345. View

10.

Evens A, Carter J, Loh K, David K . Management of older Hodgkin lymphoma patients. Hematology Am Soc Hematol Educ Program. 2019; 2019(1):233-242. PMC: 6913478. DOI: 10.1182/hematology.2019000028. View

11.

Lin S, Gao K, Gu S, You L, Qian S, Tang M . Worldwide trends in cervical cancer incidence and mortality, with predictions for the next 15 years. Cancer. 2021; 127(21):4030-4039. DOI: 10.1002/cncr.33795. View

12.

Chuan Y, Wang Y, Jin X, Ming S, Bing W, Kai W . Activation of CREB-binding protein ameliorates spinal cord injury in tabersonine treatment by suppressing NLRP3/Notch signaling. Arch Med Sci. 2023; 19(3):736-743. PMC: 10259380. DOI: 10.5114/aoms.2019.89203. View

13.

Geurts Y, Shakir R, Ntentas G, Roberti S, Aznar M, John K . Association of Radiation and Procarbazine Dose With Risk of Colorectal Cancer Among Survivors of Hodgkin Lymphoma. JAMA Oncol. 2023; 9(4):481-489. PMC: 9896374. DOI: 10.1001/jamaoncol.2022.7153. View

14.

Liang Y, Li W, Li X, Nan J . Involvement of PI3K/Akt/β-catenin signaling in schisandrin B-mitigated bone deterioration in an experimental rat model of estrogen deficiency. Arch Med Sci. 2023; 19(5):1520-1529. PMC: 10507775. DOI: 10.5114/aoms.2020.92873. View

15.

An R, Wang X, Yang L, Zhang J, Wang N, Xu F . Polystyrene microplastics cause granulosa cells apoptosis and fibrosis in ovary through oxidative stress in rats. Toxicology. 2020; 449:152665. DOI: 10.1016/j.tox.2020.152665. View

16.

Ristic L, Rancic M, Radovic M, Krtinic D, Pavlovic M, Ilic B . Melatonin inhibits apoptosis and oxidative tissue damage in cisplatin-induced pulmonary toxicity in rats. Arch Med Sci. 2024; 20(3):977-983. PMC: 11264154. DOI: 10.5114/aoms.2020.95952. View

17.

Premkumar K, Prasad S, Tiwari M, Pandey A, Gupta A, Sharma A . Meiotic Instability Generates a Pathological Condition in Mammalian Ovum. Stem Cell Rev Rep. 2020; 17(3):777-784. DOI: 10.1007/s12015-020-10072-z. View

18.

Sies H, Belousov V, Chandel N, Davies M, Jones D, Mann G . Defining roles of specific reactive oxygen species (ROS) in cell biology and physiology. Nat Rev Mol Cell Biol. 2022; 23(7):499-515. DOI: 10.1038/s41580-022-00456-z. View