Efecto protector del tirosol sobre la inflamación ovárica y el estrés oxidativo inducidos por cisplatino en ratas

• 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

Palabras clave: Ovario, cisplatino, tirosol, efecto protector, rata

Resumen

El cáncer de ovario es un tipo de cáncer muy extendido entre los cánceres ginecológicos y tiene una tasa de mortalidad muy alta. Por este motivo, continúa la búsqueda de nuevos tratamientos. El Tirosol es un compuesto fenólico con actividad antioxidante y antiinflamatoria. En el estudio, investigamos el efecto del tirosol sobre el estrés oxidativo y los parámetros inflamatorios en la inflamación ovárica y el estrés oxidativo inducidos por cisplatino en ratas. Para ello, veinticuatro ratas albinas Wistar se dividieron en cuatro grupos: control, Cisplatino, Tirosol y Cisplatino+Ttirosol. El Cisplatino se administró por vía intraperitoneal a 6 mg·kg^-1 dos veces, una vez por semana. Se administró Tirosol (20 mg·kg^-1) diariamente mediante sonda oral durante catorce d. Se midieron el estrés oxidativo y los biomarcadores inflamatorios en el tejido ovárico. La administración de Cisplatino aumentó los niveles de Malondialdehído (MDA), factor de necrosis tumoral alfa (TNF–α), interleucina 6 (IL–6) e interleucina 1 beta (IL–1β) en los ovarios, mientras que, el glutatión (GSH), la glutatión peroxidasa (GSH–Px), y los niveles de catalasa disminuyeron. Se demostró que la administración de tirosol disminuye los parámetros de estrés oxidativo y las citocinas inflamatorias. En conclusión, podemos decir que la actividad protectora del tirosol contra la inflamación ovárica y el estrés oxidativo inducidos por cisplatino se realiza a través de mecanismos antioxidantes y antiinflamatorios.

Citas

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