Protective Effect of Tyrosol on Cisplatin–Induced Ovarian Inflammation and Oxidative Stress in Rats

• İshak Gökçek Hatay Mustafa Kemal University, Faculty of Veterinary Medicine, Department of Veterinary Physiology. Hatay, Türkiye
• Ahmet Gözer Hatay Mustafa Kemal University, Faculty of Veterinary Medicine, Department of Veterinary Obstetrics and Gynaecology. Hatay, Türkiye
• Tuncer Kutlu Hatay Mustafa Kemal University, Faculty of Veterinary Medicine, Department of Veterinary Pathology. Hatay, Türkiye
• Mehmet Güvenç Hatay Mustafa Kemal University, Faculty of Veterinary Medicine, Department of Veterinary Pathology. Hatay, Türkiye
• Leyla Aydın Ankara Yıldırım Beyazıt University, Faculty of Medicine, Department of Physiology. Ankara, Türkiye
• Gökhan Uyanık Erciyes University, Faculty of Veterinary Medicine, Department of Obstetrics and Gynaecology. Kayseri, Türkiye

DOI: https://doi.org/10.52973/rcfcv-e34444

Keywords: Ovarian, cisplatin, tyrosol, protective effect, rat

Abstract

Ovarian cancer is a widespread type of cancer among gynecologic cancers and has a very high mortality rate. For this reason, the search for new treatments continues. Tyrosol is a phenolic compound with antioxidant and anti–inflammatory activity. The study, it was investigated the effect of Tyrosol on oxidative stress and inflammatory parameters in cisplatin–induced ovarian inflammation and oxidative stress in rats. For this purpose, twenty–four female Wistar albino rats were divided into four groups: control, Cisplatin, Tyrosol, and Cisplatin+Tyrosol. Cisplatin was administered intraperitoneally at 6 mg·kg^-1 twice, once a week. Tyrosol (20 mg·kg^-1) was administered daily by oral gavage for fourteen d. Oxidative stress and inflammatory biomarkers were measured in ovarian tissue. Cisplatin administration increased Malondialdehyde (MDA), tumor necrosis factor alpha (TNF–α), interleukin 6 (IL–6), and interleukin 1 beta (IL–1β) levels in the ovaries, while Glutathione (GSH), Glutathione Peroxidase (GSH–Px), and Catalase levels were decreased. Tyrosol administration was shown to decrease oxidative stress parameters and inflammatory cytokines. In conclusion, it can be say that the protective activity of Tyrosol against Cisplatin–Induced ovarian inflammation and oxidative stress is realised through antioxidant and anti–inflammatory mechanisms.

References

Dehghan M, Hoseini FS, Mohammadi Akbarabadi F, Fooladi Z, Zakeri MA. Quality of life in terminally ill cancer patients: what is the role of using complementary and alternative medicines? Support Care Cancer [Internet]. 2022; 30(11):9421–9432. doi: https://doi.org/gvbmvk

Siegel RL, Miller KD, Jemal A. Cancer statistics, 2019. CA: Cancer J. Clin. [Internet]. 2019; 69(1):7–34. doi: https://doi.org/gfs49d

Spears N, Lopes F, Stefansdottir A, Rossi V, De Felici M, Anderson RA, Klinger FG. Ovarian damage from chemotherapy and current approaches to its protection. Hum. Reprod. Update [Internet]. 2019; 25(6):673–693. doi: https://doi.org/gm4jt4

Zoń A, Bednarek I. Cisplatin in ovarian cancer treatment–known limitations in therapy force new solutions. Int. J. Mol. Sci. [Internet]. 2023; 24(8):7585. doi: https://doi.org/gt6rtw

Brown A, Kumar S, Tchounwou PB. Cisplatin–based chemotherapy of human cancers. J. Cancer Sci. Ther. [Internet]. 2019 [cited 20 May 2024]; 11(4):97. PMID: 32148661. Available in: https://goo.su/9VTIe

Bhardwaj JK, Bikal P, Sachdeva SN. Chemotherapeutic drugs induced female reproductive toxicity and treatment strategies. J. Biochem. Mol. Toxicol. [Internet]. 2023; 37(7):e23371. doi: https://doi.org/gvbmvm

Alizadehnohi M, Nabiuni M, Nazari Z, Safaeinejad Z, Irian S. The synergistic cytotoxic effect of cisplatin and honey bee venom on human ovarian cancer cell line A2780cp. J. Venom Res. [Internet]. 2012 [cited 20 May 2024]; 3:22–27. PMID: 23301148. Available in: https://goo.su/ZPGr7Uw

Meng F, Sun G, Zhong M, Yu Y, Brewer MA. Anticancer efficacy of cisplatin and trichostatin A or 5–aza–2’–deoxycytidine on ovarian cancer. Br. J. Cancer. [Internet]. 2013; 108(3):579–586. doi: https://doi.org/f4r8b6

Ayazoglu Demir E, Mentese A, Livaoglu A, Turkmen Alemdar N, Demir S. Ameliorative effect of gallic acid on cisplatin–induced ovarian toxicity in rats. Drug. Chem. Toxicol. [Internet]. 2023; 46(1):97–103. doi: https://doi.org/gvbmvn

Gabbia D, Carpi S, Sarcognato S, Zanotto I, Sayaf K, Colognesi M, Polini B, Digiacomo M, Macchia M, Nieri P, Carrara M, Cazzagon N, Russo FP, Guido M, De Martin S. The phenolic compounds tyrosol and hydroxytyrosol counteract liver fibrogenesis via the transcriptional modulation of NADPH oxidases and oxidative stress–related miRNAs. Biomed Pharmacother. [Internet]. 2023; 157:114014. doi: https://doi.org/gvbmvp

Cuffaro D, Pinto D, Silva AM, Bertolini A, Bertini S, Saba A, Macchia M, Rodrigues F, Digiacomo M. Insights into the antioxidant/antiradical effects and in vitro intestinal permeation of oleocanthal and its metabolites tyrosol and oleocanthalic acid. Molecules [Internet]. 2023; 28(13):5150. doi: https://doi.org/gvbmvq

Plotnikov MB, Plotnikova TM. Tyrosol as a neuroprotector: Strong effects of a “weak” antioxidant. Curr. Neuropharmacol. [Internet]. 2021; 19(4):434–448. doi: https://doi.org/gvbmvr

Bosetti C, Negri E, Franceschi S, Talamini R, Montella M, Conti E, Lagiou P, Parazzini F, La Vecchia C. Olive oil, seed oils and other added fats in relation to ovarian cancer (Italy). Cancer Causes Control. [Internet]. 2002; 13(5):465–470. doi: https://doi.org/fn6drm

Algandaby MM. Quercetin attenuates cisplatin–induced ovarian toxicity in rats: Emphasis on anti–oxidant, anti–inflammatory and anti–apoptotic activities. Arab. J. Chem. [Internet]. 2021; 14(7):103191. doi: https://doi.org/gvbmvs

Güvenç M, Cellat M, Gökçek İ, Arkalı G, Uyar A, Tekeli İO, Yavaş İ.Tyrosol prevents AlCl3 induced male reproductive damage by suppressing apoptosis and activating the Nrf–2/HO–1 pathway. Andrologia [Internet]. 2020; 52(2):e13499. doi: https://doi.org/gvbmvt

Arkali G, Aksakal M, Kaya ŞÖ. Protective effects of carvacrol against diabetes–induced reproductive damage in male rats: Modulation of Nrf2/HO–1 signalling pathway and inhibition of Nf–kB–mediated testicular apoptosis and inflammation. Andrologia [Internet]. 2021; 53(2):e13899. doi: https://doi.org/k4pn

Li D, Chen Y, Qi L, Ju X, Liu H, Wang G. Differentially expressed genes in cisplatin–induced premature ovarian failure in rats. Anim. Reprod. Sci. [Internet]. 2013; 137(3–4):205–213. doi: https://doi.org/f4rhcr

Said RS, Mantawy EM, El–Demerdash E. Mechanistic perspective of protective effects of resveratrol against cisplatin–induced ovarian injury in rats: emphasis on anti–inflammatory and anti–apoptotic effects. Naunyn Schmiedebergs Arch. Pharmacol. [Internet]. 2019; 392(10):1225–1238. doi: https://doi.org/gvbmvv

Eldani M, Luan Y, Xu PC, Bargar T, Kim SY. Continuous treatment with cisplatin induces the oocyte death of primordial follicles without activation. FASEB J. [Internet]. 2020; 34(10):13885–13899. doi: https://doi.org/gvbmvw

Biyik I, Ozatik FY, Albayrak M, Ozatik O, Teksen Y, Ari NS, Soysal C. The effects of recombinant klotho in cisplatin–induced ovarian failure in mice. J. Obstet. Gynaecol. Res. [Internet]. 2021; 47(5):1817–1824. doi: https://doi.org/gvbmvx

Ibrahim MA, Albahlol IA, Wani FA, Abd–Eltawab Tammam A, Kelleni MT, Sayeed MU, Abd El–Fadeal NM, Mohamed AA. Resveratrol protects against cisplatin–induced ovarian and uterine toxicity in female rats by attenuating oxidative stress, inflammation and apoptosis. Chem. Biol. Interact. [Internet]. 2021; 338:109402. doi: https://doi.org/gq3tr7

Song M, Cui M, Liu K. Therapeutic strategies to overcome cisplatin resistance in ovarian cancer. Eur. J. Med. Chem. [Internet]. 2022; 232:114205. doi: https://doi.org/gtmxpj

Torić J, Marković AK, Brala CJ, Barbarić M. Anticancer effects of olive oil polyphenols and their combinations with anticancer drugs. Acta Pharm. [Internet]. 2019; 69(4):461–482. doi: https://doi.org/gvbmvz

Xu X, Chen X, Zhang X, Liu Y, Wang Z, Wang P, Du Y, Qin Y, Chen ZJ. Impaired telomere length and telomerase activity in peripheral blood leukocytes and granulosa cells in patients with biochemical primary ovarian insufficiency. Hum. Reprod. 2017; 32(1):201–207. [Internet]. doi: https://doi.org/gvbmv2

Melekoglu R, Ciftci O, Eraslan S, Cetin A, Basak N. Beneficial effects of curcumin and capsaicin on cyclophosphamide–induced premature ovarian failure in a rat model. J. Ovarian Res. [Internet]. 2018; 11(33):1–8. doi: https://doi.org/gsbrm5

Di Benedetto R, Varì R, Scazzocchio B, Filesi C, Santangelo C, Giovannini C, Matarrese P, D’Archivio M, Masella R. Tyrosol, the major extra virgin olive oil compound, restored intracellular antioxidant defences in spite of its weak antioxidative effectiveness. Nutr. Metab. Cardiovasc. Dis. [Internet]. 2007; 17(7):535–545. doi: https://doi.org/fjhmp2

Sami DH, Soliman AS, Khowailed AA, Alruhaimi RS, Hassanein EHM, Kamel EM, Mahmoud AM. The protective effect of 7–hydroxycoumarin against cisplatin–induced liver injury is mediated via attenuation of oxidative stress and inflammation and upregulation of Nrf2/HO–1 pathway. Environ. Sci. Pollut. Res. Int. [Internet]. 2023; 30(33):80181–80191. doi: https://doi.org/gvbmv3

Yang L, Chen Y, Liu Y, Xing Y, Miao C, Zhao Y, Chang X, Zhang Q. The role of oxidative stress and natural antioxidants in ovarian aging. Front. Pharmacol. [Internet]. 2021; 11:617843. doi: https://doi.org/gvbmv4

So H, Kim H, Lee JH, Park C, Kim Y, Kim E, Kim JK, Yun KJ, Lee KM, Lee HY, Moon SK, Lim DJ, Park R. Cisplatin cytotoxicity of auditory cells requires secretions of proinflammatory cytokines via activation of ERK and NF–κB. J. Assoc. Res. Otolaryngol. [Internet]. 2007; 8(3):338–355. doi: https://doi.org/d9wckd

Han Z, Feng J, Hong Z, Chen L, Li W, Liao S, Wang X, Ji T, Wang S, Ma D, Chen G, Gao Q. Silencing of the STAT3 signaling pathway reverses the inherent and induced chemoresistance of human ovarian cancer cells. Biochem. Biophys. Res. Commun. [Internet]. 2013; 435(2):188–194. doi: https://doi.org/f4z2m5

Souza PAL, Marcadenti A, Portal VL. Effects of olive oil phenolic compounds on inflammation in the prevention and treatment of coronary artery disease. Nutrients [Internet]. 2017; 9(10):1087. doi: https://doi.org/gvbmv5

Serreli G, Deiana M. Extra virgin olive oil polyphenols: modulation of cellular pathways related to oxidant species and inflammation in aging. Cells [Internet]. 2020; 9(2):478. doi: https://doi.org/ghdhm7

Hu X, Wang M, Shahidi, F. Antiglycative and anti–inflammatory effects of lipophilized tyrosol derivatives. Food Prod. Process. Nutr. [Internet]. 2020; 2(28):1–7. doi: https://doi.org/gvbmv6