Protective Effects of D-Carvone on Ovarian Ischemia-Reperfusion Injury: An Experimental Study

Year 2025, Volume: 15 Issue: 3, 311 - 319, 05.01.2026

Saime Özbek Şebin , Ayhan Tanyeli , Başak Gülakar , Mustafa Can Güler , Esra Laloğlu , Selim Çomaklı

Abstract

Aim: The aim of this study was to measure the protective efficacy of D-carvone against ovarian ischemia-reperfusion (OIR) injury by evaluating apoptosis, inflammation, and oxidative stress.
Material and Methods: 24 Wistar albino female rats were randomly divided into three groups with eight animals in each group. In the sham group, a lower abdominal incision was made. In the ovarian ischemia-reperfusion (OIR) group, 3 hours of ischemia followed by 3 hours of reperfusion were applied. In the OIR+Dcarvone group, 20 mg/kg D-carvone was administered intraperitoneally for 14 days. On day 15, after 3 hours of ovarian ischemia, 3 hours of reperfusion were performed by administering the last dose of D-carvone just before reperfusion. ELISA and immunohistological analyses were performed on the ovarian tissues.
Results: TNF-α, IL-1β, IL-6, malondialdehyde (MDA), myeloperoxidase (MPO), total oxidative level (TOS), oxidative stress index (OSI), and ischemia-modified albumin (IMA) levels, which were higher in the OIR group compared to the sham group, decreased significantly in the OIR+D-Carvone group. IL-10, total antioxidant level (TAS), glutathione (GSH), and catalase (CAT) levels were significantly higher in the D-carvone-treated group compared to the OIR group and lower in the OIR group compared to the sham group. Ischemia-modified albumin levels of the OIR+D-carvone group were significantly lower compared to the OIR group. 8-OHdG and NFκB, which rise with ischemia reperfusion (IR) injury, were reduced considerably in the treatment group. Caspase 3 immunopositivity is significantly lower in the OIR+D-carvone group compared to OIR.
Conclusion: In the present study, D-carvone showed anti-inflammatory and antioxidant effects against OIR injury, and protective activity was determined. These results suggested that D-carvone may be a potential agent for OIR injury.

Keywords

ovary ischemia reperfusion , oxidative stress , inflammation , apoptosis

References

• 1. Guile SL, Mathai JK. Ovarian torsion. 2020.
• 2. Huchon C, Fauconnier A. Adnexal torsion: a literature review. Eur J Obstet Gynecol Reprod Biol. May. 2010;150(1):8–12.
• 3. Yigit S, Yesilyurt I, Bitiktas S, et al. Therapeutic effect of Berberis vulgaris fruit extract on histopathological changes and oxidative stress markers of ovarian ischemia and reperfusion injury in rats. 2024;36(11):103578.
• 4. Bridwell RE, Koyfman A, Long B. High risk and low prevalence diseases: Ovarian torsion. Am J Emerg Med. Jun. 2022;56:145150.
• 5. Armin Akış P, Tanyeli A, Ekinci Akdemir FN, et al. Costunolide, an effective agent against oxidative damage, apoptosis and autophagy in the ovarian torsion/detorsion model. Arch Physiol Biochem. Apr. 2025;131(2):265–273.
• 6. Ogaly HA, Aldulmani SAA, Al-Zahrani FAM, Abd-Elsalam RM. D-Carvone Attenuates CCl(4)-Induced Liver Fibrosis in Rats by Inhibiting Oxidative Stress and TGF-ß 1/SMAD3 Signaling Pathway. Biology (Basel) . May 12. 2022;11(5)
• 7. Irshad R, Batool F, Raj N, et al. Multi-targeted effects of D-carvone against Non-Small Cell Lung Cancer (NSCLC): A network pharmacology-based study. Toxicol Appl Pharmacol. Jun. 2024;487:116978.
• 8. Sharma S, Gao P, Steele VE. Quantitative morphometry of respiratory tract epithelial cells as a tool for testing chemopreventive agent efficacy. Anticancer Res. Mar. 2010;30(3):737–42.
• 9. Vinothkumar R, Nalini N. Supplementation with D-carvone Induces Cytotoxicity and Mitochondrial-Mediated Apoptosis in Human Colon Cancer Cell Lines HT-29 and SW480. IJPBA. 2013;4(2):502–510.
• 10. Lima CF, Carvalho F, Fernandes E, et al. Evaluation of toxic/ protective effects of the essential oil of Salvia officinalis on freshly isolated rat hepatocytes. Toxicology in vitro. 2004;18(4):457465.
• 11. Takeda A, Hayashi S, Teranishi Y, Imoto S, Nakamura H. Chronic adnexal torsion: An under-recognized disease entity. Eur J Obstet Gynecol Reprod Biol. Mar. 2017;210:45–53.
• 12. Robertson JJ, Long B, Koyfman A. Myths in the Evaluation and Management of Ovarian Torsion. J Emerg Med. Apr. 2017;52(4):449–456.
• 13. Gulakar B, Sebin SO, Laloglu E, et al. New Potential Agent in Ovarian Ischemia Reperfusion Injury: Alpha Pinene. J Biochem Mol Toxicol. Jun. 2025;39(6):e70318.
• 14. Wu MY, Yiang GT, Liao WT, et al. Current Mechanistic Concepts in Ischemia and Reperfusion Injury. Cell Physiol Biochem. 2018;46(4):1650–1667.
• 15. Gencer M, Karaca T, Güngör AN, et al. The protective effect of quercetin on IMA levels and apoptosis in experimental ovarian ischemia-reperfusion injury. Eur J Obstet Gynecol Reprod Biol. Jun. 2014;177:135–40.
• 16. Cakir E, Ozbek M, Ozkaya E, et al. Oxidative stress markers are not valuable markers in lean and early age of polycystic ovary syndrome patients. J Endocrinol Invest. Jul-Aug. 2011;34(7):e178–82.
• 17. Bouyahya A, Mechchate H, Benali T, et al. Health Benefits and Pharmacological Properties of Carvone. Biomolecules. Dec 1. 2021;11(12)
• 18. Aydın E, Türkez H, Keleş MS. Potential anticancer activity of carvone in N2a neuroblastoma cell line. Toxicology and industrial health. 2015;31(8):764–772.
• 19. Rajeshwari T, Raja B. D-carvone, a monoterpene reverses alterations in heart rate, nitric oxide, aortic lipids and enzymatic antioxidant status in nitric oxide deficient hypertensive rats. International Letters of Natural Sciences. 2015;5.
• 20. Ulaş N, Üstündağ H, Özkanlar S, Erbaş E, Kara A, Özkanlar Y. D-carvone attenuates LPS-induced acute lung injury via TLR4/ NF-κB and Nrf2/HO-1 signaling pathways in rats. Naunyn Schmiedebergs Arch Pharmacol. Mar 21. 2025;
• 21. Mohamed ME, Younis NS. Ameliorative Effect of D-Carvone against Hepatic Ischemia-Reperfusion-Induced Injury in Rats. Life (Basel) . Sep 27. 2022;12(10)
• 22. Dai M, Wu L, Yu K, et al. D-Carvone inhibit cerebral ischemia/reperfusion induced inflammatory response TLR4/ NLRP3 signaling pathway. Biomed Pharmacother. Dec. 2020;132:110870.