{"status":"ok","message-type":"work","message-version":"1.0.0","message":{"indexed":{"date-parts":[[2026,5,13]],"date-time":"2026-05-13T19:37:38Z","timestamp":1778701058578,"version":"3.51.4"},"reference-count":35,"publisher":"MDPI AG","issue":"9","license":[{"start":{"date-parts":[[2024,8,27]],"date-time":"2024-08-27T00:00:00Z","timestamp":1724716800000},"content-version":"vor","delay-in-days":0,"URL":"https:\/\/creativecommons.org\/licenses\/by\/4.0\/"}],"content-domain":{"domain":[],"crossmark-restriction":false},"short-container-title":["Medicina"],"abstract":"<jats:p>Background and Objectives: Cisplatin is a chemotherapeutic drug that is frequently used with hyperthermic intraperitoneal chemotherapy (HIPEC). Cisplatin-induced gonadotoxicity leads to a depletion of the ovarian reserve, causing premature ovarian insufficiency. This study aimed to investigate the impact of hyperthermia on cisplatin-induced ovarian toxicity and to determine whether sevoflurane or desflurane could be a more appropriate choice of anesthetic for reducing ovarian toxicity in HIPEC procedures. Materials and Methods: A total of 24 New Zealand rabbits were randomly divided into 4 groups as follows: Group H: HIPEC (cisplatin 7 mg\/kg), Group HS: HIPEC (cisplatin 7 mg\/kg) + 3% sevoflurane (2 h), Group HD: HIPEC (cisplatin 7 mg\/kg) + 6% desflurane (2 h), and Group C: Control (Saline). Two catheters were placed in the abdominal cavity, the upper and lower quadrants. The perfusate was heated to 42 \u00b0C and given intraperitoneally for 90 min at a rate of 4 mL\/min by catheters. Ovarian tissues were collected for Hematoxylin and Eosin staining and immunohistochemical analysis. Results: The primary follicle number was significantly decreased in Group H and HD compared to the C group (p &lt; 0.05). Bax expression was high in Group H, according to all groups (p &lt; 0.0001). Bax expression significantly decreased after sevoflurane, compared to group H (p = 0.012). The bcl-2 expression decreased in all groups compared to the C group. Bcl-2 expression was increased with sevoflurane compared to the H group (p = 0.001). Caspase 3 and p53 expression increased in all groups compared to the C group. p53 expression was decreased with sevoflurane and desflurane compared to the H group (p = 0.002, p = 0.008, respectively). Conclusions: The application of cisplatin with the intraoperative HIPEC method caused ovarian damage. According to our results, sevoflurane anesthesia could be a better option in mitigating cell death I the n ovarian reserve (follicle count) and apoptosis in the HIPEC procedures. We think that our findings should be supported by large series of clinical and experimental studies.<\/jats:p>","DOI":"10.3390\/medicina60091403","type":"journal-article","created":{"date-parts":[[2024,8,27]],"date-time":"2024-08-27T06:19:01Z","timestamp":1724739541000},"page":"1403","update-policy":"https:\/\/doi.org\/10.3390\/mdpi_crossmark_policy","source":"Crossref","is-referenced-by-count":2,"title":["Evaluation of the Effect of Different Inhalation Agents on Ovaries with Hyperthermic Intraperitoneal Chemotherapy: An Experimental Study"],"prefix":"10.3390","volume":"60","author":[{"given":"\u00d6zlem","family":"\u015een","sequence":"first","affiliation":[{"name":"Department of Anesthesiology and Reanimation, Trabzon Kanuni Training and Research Hospital, Trabzon 61250, Turkey"}],"role":[{"role":"author","vocabulary":"crossref"}]},{"given":"Esra","family":"Aslan","sequence":"additional","affiliation":[{"name":"Department of Histology and Embryology, Faculty of Medicine, Afyonkarahisar Health Sciences University, Afyonkarahisar 030030, Turkey"}],"role":[{"role":"author","vocabulary":"crossref"}]},{"given":"Dilek","family":"Kalayc\u0131","sequence":"additional","affiliation":[{"name":"Department of Anesthesiology and Reanimation, Ankara A.Y. Oncology Training and Research Hospital, Ankara 06200, Turkey"}],"role":[{"role":"author","vocabulary":"crossref"}]},{"given":"Ay\u015feg\u00fcl","family":"K\u00fc\u00e7\u00fck","sequence":"additional","affiliation":[{"name":"Department of Physiology, Faculty of Medicine, Kutahya Health Sciences University, K\u00fctahya 43110, Turkey"}],"role":[{"role":"author","vocabulary":"crossref"}]},{"given":"Semih","family":"Ba\u015fkan","sequence":"additional","affiliation":[{"name":"Department of Anesthesiology and Reanimation, Faculty of Medicine, Ankara Y\u0131ld\u0131r\u0131m Beyazit University, Ankara 06800, Turkey"}],"role":[{"role":"author","vocabulary":"crossref"}]},{"given":"\u015eaban Cem","family":"Sezen","sequence":"additional","affiliation":[{"name":"Department of Histology and Embryology, Faculty of Medicine, K\u0131r\u0131kkale University, K\u0131r\u0131kkale 71450, Turkey"}],"role":[{"role":"author","vocabulary":"crossref"}]},{"ORCID":"https:\/\/orcid.org\/0000-0003-4882-5063","authenticated-orcid":false,"given":"Mustafa","family":"Arslan","sequence":"additional","affiliation":[{"name":"Department of Anesthesiology and Reanimation, Faculty of Medicine, Gazi University, Ankara 06560, Turkey"}],"role":[{"role":"author","vocabulary":"crossref"}]},{"given":"Yusuf","family":"\u00dcnal","sequence":"additional","affiliation":[{"name":"Department of Anesthesiology and Reanimation, Faculty of Medicine, Gazi University, Ankara 06560, Turkey"}],"role":[{"role":"author","vocabulary":"crossref"}]},{"given":"Murat","family":"Tosun","sequence":"additional","affiliation":[{"name":"Department of Histology and Embryology, Faculty of Medicine, Afyonkarahisar Health Sciences University, Afyonkarahisar 030030, Turkey"}],"role":[{"role":"author","vocabulary":"crossref"}]}],"member":"1968","published-online":{"date-parts":[[2024,8,27]]},"reference":[{"key":"ref_1","doi-asserted-by":"crossref","first-page":"3373","DOI":"10.2147\/OTT.S309285","article-title":"Efficacy and Safety of Systemic and Locoregional Cisplatin Chronotherapy in Rats with Ovarian Carcinoma","volume":"14","author":"Kireeva","year":"2021","journal-title":"Onco Targets Ther."},{"key":"ref_2","first-page":"270","article-title":"The impact of hyperthermic intraperitoneal chemotherapy and cytoreductive surgery on clinical outcomes and quality of life of patients with peritoneal carcinomatosis","volume":"25","author":"Bondar","year":"2021","journal-title":"Contemp. Oncol."},{"key":"ref_3","doi-asserted-by":"crossref","first-page":"419","DOI":"10.1080\/02656736.2017.1279757","article-title":"Targeting therapy-resistant cancer stem cells by hyperthermia","volume":"33","author":"Oei","year":"2017","journal-title":"Int. J. Hyperth."},{"key":"ref_4","doi-asserted-by":"crossref","unstructured":"Kong, X.X., Jiang, S., Liu, T., Liu, G.F., and Dong, M. (2020). Paclitaxel increases sensitivity of SKOV3 cells to hyperthermia by inhibiting heat shock protein 27. Biomed. Pharmacother., 132.","DOI":"10.1016\/j.biopha.2020.110907"},{"key":"ref_5","doi-asserted-by":"crossref","first-page":"681","DOI":"10.1080\/02656730500307298","article-title":"How do cells respond to their thermal environment?","volume":"21","author":"Lepock","year":"2005","journal-title":"Int. J. Hyperth."},{"key":"ref_6","doi-asserted-by":"crossref","first-page":"235","DOI":"10.1038\/bjc.1994.45","article-title":"Response of peritoneal solid tumours after intraperitoneal chemohyperthermia treatment with cisplatin or carboplatin","volume":"69","author":"Los","year":"1994","journal-title":"Br. J. Cancer"},{"key":"ref_7","doi-asserted-by":"crossref","first-page":"272","DOI":"10.3109\/09513590.2014.984679","article-title":"Protective effects of sildenafil citrate administration on cisplatin-induced ovarian damage in rats","volume":"31","author":"Taskin","year":"2015","journal-title":"Gynecol. Endocrinol."},{"key":"ref_8","doi-asserted-by":"crossref","first-page":"11","DOI":"10.1093\/toxres\/tfaa091","article-title":"4-Hydroxyhalcone effects on cisplatin-induced genotoxicity model","volume":"10","author":"Nazari","year":"2021","journal-title":"Toxicol. Res."},{"key":"ref_9","doi-asserted-by":"crossref","first-page":"673","DOI":"10.1093\/humupd\/dmz027","article-title":"Ovarian damage from chemotherapy and current approaches to its protection","volume":"25","author":"Spears","year":"2019","journal-title":"Hum. Reprod. Update"},{"key":"ref_10","doi-asserted-by":"crossref","first-page":"327240","DOI":"10.1155\/2013\/327240","article-title":"The effect of mirtazapine on cisplatin-induced oxidative damage and infertility in rat ovaries","volume":"2013","author":"Altuner","year":"2013","journal-title":"Sci. World J."},{"key":"ref_11","doi-asserted-by":"crossref","first-page":"859","DOI":"10.1097\/00003643-200311000-00002","article-title":"Anaesthetic implications of anticancer chemotherapy","volume":"20","author":"Kvolik","year":"2003","journal-title":"Eur. J. Anaesthesiol."},{"key":"ref_12","doi-asserted-by":"crossref","first-page":"337","DOI":"10.1159\/000218066","article-title":"Genotoxicity and cytotoxicity of cisplatin treatment combined with anaesthetics on EAT cells in vivo","volume":"32","author":"Brozovic","year":"2009","journal-title":"Onkologie"},{"key":"ref_13","doi-asserted-by":"crossref","first-page":"1","DOI":"10.1159\/000417211","article-title":"TheMetabolismandToxicity of Fluoride","volume":"13","author":"Whitford","year":"1989","journal-title":"Monogr. Oral Sci."},{"key":"ref_14","unstructured":"Fitzgerald, S.P., Campell, J.J., and Lamount, J.V. (1992, January 20\u201323). The establishment of reference ranges for selenium. Seleno enzyme glutathione peroxidase and metallo enzyme superoxide dismutase in blood fractions. Proceedings of the Fifth International Syposium on Selenium in Biology and Medicine, Nashville, TN, USA."},{"key":"ref_15","first-page":"371","article-title":"Oxidant and antioxidant activities of different anesthetic techniques. Propofol versus desflurane","volume":"30","author":"Ceylan","year":"2009","journal-title":"Saudi Med. J."},{"key":"ref_16","doi-asserted-by":"crossref","first-page":"366","DOI":"10.1111\/j.1600-0773.1994.tb00376.x","article-title":"In vivo and in vitro sevoflurane-induced lipid peroxidation in guinea-pig liver microsomes","volume":"75","author":"Sato","year":"1994","journal-title":"Pharmacol. Toxicol."},{"key":"ref_17","doi-asserted-by":"crossref","first-page":"113","DOI":"10.2478\/10004-1254-62-2011-2096","article-title":"Oxidative and antioxidative effects of desflurane and sevoflurane on rat tissue in vivo","volume":"62","author":"Aydin","year":"2011","journal-title":"Arh. Hig. Rada Toksikol."},{"key":"ref_18","doi-asserted-by":"crossref","first-page":"348","DOI":"10.1097\/ACO.0b013e32835347b2","article-title":"Anesthetic management in patients undergoing hyperthermic chemotherapy","volume":"25","author":"Raspe","year":"2012","journal-title":"Curr. Opin. Anaesthesiol."},{"key":"ref_19","doi-asserted-by":"crossref","first-page":"71","DOI":"10.1080\/01913123.2019.1711479","article-title":"Investigation of the preventive effects of dehydroepiandrosterone (DHEA) and Caffeic acid phenethyl ester (CAPE) on cisplatin-induced ovarian damage in rats","volume":"44","author":"Sakin","year":"2020","journal-title":"Ultrastruct. Pathol."},{"key":"ref_20","doi-asserted-by":"crossref","first-page":"379","DOI":"10.1016\/j.bpobgyn.2011.11.008","article-title":"Chemotherapy and fertility","volume":"26","author":"Blumenfeld","year":"2012","journal-title":"Best Pr. Res. Clin. Obstet. Gynaecol."},{"key":"ref_21","doi-asserted-by":"crossref","first-page":"1225","DOI":"10.1007\/s00210-019-01662-x","article-title":"Mechanistic perspective of protective effects of resveratrol against cisplatin-induced ovarian injury in rats: Emphasis on anti-inflammatory and anti-apoptotic effects","volume":"392","author":"Said","year":"2019","journal-title":"Naunyn-Schmiedebergs Arch. Pharmacol."},{"key":"ref_22","doi-asserted-by":"crossref","first-page":"738","DOI":"10.1016\/j.ijrobp.2004.11.038","article-title":"Predicting age of ovarian failure after radiation to a field that includes the ovaries","volume":"62","author":"Wallace","year":"2005","journal-title":"Int. J. Radiat. Oncol. Biol. Phys."},{"key":"ref_23","doi-asserted-by":"crossref","first-page":"72","DOI":"10.1038\/cdd.2016.97","article-title":"LH prevents cisplatin-induced apoptosis in oocytes and preserves female fertility in mouse","volume":"24","author":"Rossi","year":"2017","journal-title":"Cell Death Differ."},{"key":"ref_24","doi-asserted-by":"crossref","unstructured":"Morgan, S., Lopes, F., Gourley, C., Anderson, R.A., and Spears, N. (2013). Cisplatin and doxorubicin induce distinct mechanisms of ovarian follicle loss; imatinib provides selective protection only against cisplatin. PLoS ONE, 8.","DOI":"10.1371\/journal.pone.0070117"},{"key":"ref_25","doi-asserted-by":"crossref","first-page":"251","DOI":"10.1093\/humupd\/dmh021","article-title":"Fertility preservation in female patients","volume":"10","author":"Sonmezer","year":"2004","journal-title":"Hum. Reprod. Update"},{"key":"ref_26","doi-asserted-by":"crossref","first-page":"6","DOI":"10.1111\/j.1479-828X.2004.00143.x","article-title":"Effect of chemotherapy on primordial follicular reserve of rat: An animal model of premature ovarian failure and infertility","volume":"44","author":"Yucebilgin","year":"2004","journal-title":"Aust. N. Z. J. Obstet. Gynaecol."},{"key":"ref_27","doi-asserted-by":"crossref","first-page":"1384","DOI":"10.1111\/j.1471-0528.2005.00670.x","article-title":"Antral follicle count, anti-mullerian hormone and inhibin B: Predictors of ovarian response in assisted reproductive technology?","volume":"112","author":"Muttukrishna","year":"2005","journal-title":"BJOG"},{"key":"ref_28","doi-asserted-by":"crossref","first-page":"981","DOI":"10.1097\/00000539-200110000-00036","article-title":"Oxidative stress status during exposure to propofol, sevoflurane and desflurane","volume":"93","author":"Allaouchiche","year":"2001","journal-title":"Anesth. Analg."},{"key":"ref_29","doi-asserted-by":"crossref","first-page":"525","DOI":"10.1093\/humupd\/dms022","article-title":"How do chemotherapeutic agents damage the ovary?","volume":"18","author":"Morgan","year":"2012","journal-title":"Hum. Reprod. Update"},{"key":"ref_30","doi-asserted-by":"crossref","first-page":"90","DOI":"10.1016\/j.critrevonc.2017.03.009","article-title":"Mechanisms of chemotherapy-induced ovarian damage in breast cancer patients","volume":"113","author":"Peccatori","year":"2017","journal-title":"Crit. Rev. Oncol. Hematol."},{"key":"ref_31","doi-asserted-by":"crossref","first-page":"23","DOI":"10.3892\/or.2021.7974","article-title":"Direct and indirect anticancer effects of hyperthermic intraperitoneal chemotherapy on peritoneal malignancies (Review)","volume":"45","author":"Zhang","year":"2021","journal-title":"Oncol. Rep."},{"key":"ref_32","doi-asserted-by":"crossref","first-page":"2369","DOI":"10.1016\/j.lfs.2004.12.052","article-title":"Effects of inhalation anesthetics halothane, sevoflurane, and isoflurane on human cell lines","volume":"77","author":"Kvolik","year":"2005","journal-title":"Life Sci."},{"key":"ref_33","first-page":"369","article-title":"Genotoxicity of inhalation anaesthetics: DNA lesions generated by sevoflurane in vitro and in vivo","volume":"45","author":"Szyfter","year":"2004","journal-title":"J. Appl. Genet."},{"key":"ref_34","doi-asserted-by":"crossref","first-page":"642","DOI":"10.1017\/S0265021508004171","article-title":"Evaluation of DNA damage in vivo induced by combined application of cisplatin and sevoflurane","volume":"25","author":"Brozovic","year":"2008","journal-title":"Eur. J. Anaesthesiol."},{"key":"ref_35","doi-asserted-by":"crossref","first-page":"1467","DOI":"10.1097\/00000542-200112000-00028","article-title":"Inhalation anesthetics induce apoptosis in normal peripheral lymphocytes in vitro","volume":"95","author":"Matsuoka","year":"2001","journal-title":"Anesthesiology"}],"container-title":["Medicina"],"original-title":[],"language":"en","link":[{"URL":"https:\/\/www.mdpi.com\/1648-9144\/60\/9\/1403\/pdf","content-type":"unspecified","content-version":"vor","intended-application":"similarity-checking"}],"deposited":{"date-parts":[[2025,10,10]],"date-time":"2025-10-10T15:43:25Z","timestamp":1760111005000},"score":1,"resource":{"primary":{"URL":"https:\/\/www.mdpi.com\/1648-9144\/60\/9\/1403"}},"subtitle":[],"short-title":[],"issued":{"date-parts":[[2024,8,27]]},"references-count":35,"journal-issue":{"issue":"9","published-online":{"date-parts":[[2024,9]]}},"alternative-id":["medicina60091403"],"URL":"https:\/\/doi.org\/10.3390\/medicina60091403","relation":{},"ISSN":["1648-9144"],"issn-type":[{"value":"1648-9144","type":"electronic"}],"subject":[],"published":{"date-parts":[[2024,8,27]]}}}