Kurkumin ve beta-karotenin sisplatinin neden olduğu over hasarı üzerindeki etkilerinin karşılaştırılması

Yıl 2023, Cilt: 48 Sayı: 4, 1248 - 1257, 29.12.2023

Ayşe Ceyhan , Münevver Baran , Pınar Alişan Suna , Özge Cengiz Mat , Arzu Yay

https://doi.org/10.17826/cumj.1345688

Öz

Amaç: Cisplatin (CIS) kaynaklı over hasarına karşı kurkumin (CUR) ve beta-karotenin (BC) potansiyel koruyucu etkilerinin histolojik ve immünohistokimyasal yöntemlerle araştırılması amaçlanmıştır.
Gereç ve Yöntem: Çalışmada, rastgele yedi gruba ayrılan 56 dişi Wistar albino sıçan kullanıldı. Kontrol sıçanları herhangi bir tedavi görmedi; sham grubuna gavajla 1 ml/kg susam yağı verildi; CIS grubuna 5 mg/kg CIS; CUR grubuna 200 mg/kg CUR; BC grubuna 200 mg/kg BC; CUR + CIS grubuna, CUR uygulamasından sonra CIS uygulandı; BC + CIS grubu, BC ile ön işleme tabi tutuldu, ardından CIS uygulandı. Tüm grupların overleri son uygulamadan beş gün sonra eksize edildi. Elde edilen dokularda, histopatolojik değerlendirme yapıldı ve folikül rezervi hesaplandı. Anti-Mullerian hormon (AMH) ve nükleer faktör-kappa B (NF-κB) ekspresyonu immünohistokimyasal olarak saptandı. Apoptoz ise, TUNEL yöntemi kullanılarak değerlendirildi.
Bulgular: CUR ve BC'nin, CIS'in neden olduğu azalan primordial, primer, preantral, sekonder ve tersiyer folikül sayılarına karşı koruyucu olduğu gözlendi. AMH immünoreaktivitesi, kontrol ve CUR + CIS grupları için hemen hemen aynıydı. CUR ve BC gruplarında kontrollere kıyasla over NF-κB ekspresyon seviyelerini düşürdü. TUNEL pozitif apoptotik hücre sayıları, CUR'nin BC'den daha güçlü bir anti-apoptotik etki gösterdiğini gösterdi.
Sonuç: CIS’nin neden olduğu over hasarına karşı CUR'nin BC'den daha fazla antioksidan ve antiinflamatuar etkiye sahip olduğunu gösterilmiştir.

Anahtar Kelimeler

Anti-Mullerian hormone, apoptosis, beta-karoten, cisplatin, kurkumin, NF-κB

Proje Numarası

project no. TYL-2016-7069

Comparison of effects of curcumin and beta-carotene on ovarian damage caused by cisplatin

Öz

Purpose: We aimed the potential protective effects of curcumin (CUR) and beta-carotene (BC) against cisplatin (CIS)-induced ovarian damage using histological and immunohistochemical methods.
Materials and Methods: We used 56 female Wistar albino rats, divided randomly into seven groups. Control rats did not receive any treatment; the sham group was administered 1 ml/kg sesame oil by gavage; the CIS group 5 mg/kg CIS; the CUR group 200 mg/kg CUR; the BC group 100 mg/kg BC; the CUR + CIS group, CIS after administration of CUR; the BC + CIS group was pretreated with BC, then administered CIS. The ovaries of all groups were excised five days after the last application. We assessed histopathology and counted and classified follicles. Expression of anti-Mullerian hormone (AMH) and nuclear factor-kappa B (NF-κB) was detected immunohistochemically. Apoptosis was evaluated using the TUNEL method.
Results: CUR and BC are protective against decreased numbers of primordial, primary, preantral, secondary, and tertiary follicles caused by CIS. Both Cur and BC reduced ovarian NF-κB levels in comparison to the control group, and AMH immunoreactivity was almost identical for the control and CUR + CIS groups. Apoptotic cell counts indicated that CUR exerts a stronger anti-apoptotic effect than BC.
Conclusion: CUR has a protective effect against ovarian damage brought on by CIS and greater antioxidant and anti-inflammatory properties than BC.

Anahtar Kelimeler

Anti-Mullerian hormon, Apoptosis, beta-karoten, cisplatin, kurkumin, NF-κB

Destekleyen Kurum

This study was supported by grants from the Erciyes University Scientific Research Projects Unit

Proje Numarası

project no. TYL-2016-7069

Kaynakça

• Hansen KR, Knowlton NS, Thyer AC, Charleston JS, Soules MR, Klein NA. A new model of reproductive aging: the decline in ovarian non-growing follicle number from birth to menopause. Hum Reprod. 2008;23:699–708.
• Rossi V, Lispi M, Longobardi S, Mattei M, Di Rella F, Salustri A et al. LH prevents cisplatin-induced apoptosis in oocytes and preserves female fertility in mouse. Cell Death Differ. 2017;24:72–82.
• Brown A, Kumar S, Tchounwou P. Cisplatin-based chemotherapy of human cancers. J Cancer Sci Ther. 2011;11:97–103.
• Gouveia BB, Barberino RS, Menezes VG, Monte APO, Silva RLS, Palheta RC Jr et al. Amburana cearensis leaf extract protects against cisplatin-induced ovarian damage through regulation of p-PTEN and p-Akt proteins in mice. Iran J Basic Med Sci. 2022;25:683-9.
• Gąsiorkiewicz BM, Koczurkiewicz-Adamczyk P, Piska K, Pękala E. Autophagy modulating agents as chemosensitizers for cisplatin therapy in cancer. Invest New Drugs. 2021;39:538-63.
• Anderson RA, Clatot F, Demeestere I, Lambertini M, Morgan A, Nelson SM et al. Cancer survivorship: Reproductive health outcomes should be included in standard toxicity assessments. Eur J Cancer. 2021;144:310-16.
• Pandya U, Saini MK, Jin GF, Awasthi S, Godley BF, Awasthi YC. Dietary curcumin prevents ocular toxicity of naphthalene in rats. Toxicol Lett. 2000;115:195-204.
• Farombi EO, Ekor M. Curcumin attenuates gentamicin-induced renal oxidative damage in rats. Food Chem Toxicol. 2006;44:1443-8.
• Menon VP, Sudheer AR. Antioxidant and anti-inflammatory properties of Curcumin. Adv Exp Med Biol. 2007;595:105–25.
• Devasena T, Rajasekaran KN, Menon VP. Bis‑1,7‑(2‑hydroxyphenyl)‑hepta‑1,6‑diene‑3,5‑dione (a curcumin analog) ameliorates DMH‑induced hepatic oxidative stress during colon carcinogenesis. Pharmacol Res. 2002;46:39‑45.
• El-Demerdash FM, Yousef MI, Kedwany FS, Baghdadi HH. Cadmium-induced changes in lipid peroxidation, blood hematology, biochemical parameters and semen quality of malerats: protective role of vitamin E and beta-carotene. Food Chem Toxicol. 2004;42:1563–71.
• Codoner-Franch P, Muniz P, Gasco E, Domingo JV, Valls-Belles V. Effect of diet supplemented with alpha-tocopherol and beta-carotene on ATP andantioxidant levels after hepatic ischemia-reperfusion. J Clin Biochem Nutr. 2008;43:13-18.
• Hosseini F, Naseri MK, Badavi M, Ghaffari MA, Shahbazian H, Rashidi I. Effect of beta carotene on lipid peroxidation and antioxidant status following renal ischemia/reperfusion injury in rat. Scand J Clin Lab Invest. 2010;70:259-63.
• Taskın MI, Yay A, Adalı E, Balcıoglu E, Inceboz U. Protective effects of sildenafil citrate administration on cisplatin induced ovarian damage in rats. Gynecol Endocrinol. 2015;31:272-7.
• Soleimani H, Abdollah A, Taheri S, Sajadi E, Shafikhani S, Schuger LA et al. The effect of combined photobiomodulation and curcumin on skin wound healing in type I diabetes in rats. J Photochem Photobiol B. 2018;181:23-30.
• Eser A, Hizli D, Haltas H, Namuslu M, Kosus A, Kosus N et al. Effects of curcumin on ovarian ischemia-reperfusion injury in a rat model. Biomed Rep. 2015;3:807-13.
• Karamese Aksak S, Toktay E, Unal D, Sellik J, Karamese M, Malkoc I. The protective effects of beta-carotene against ischemia/reperfusion injury in rat ovarian tissue. Acta Histochem. 2015;117:790-7.
• Sonmezer M, Oktay K. Fertility reservation in female patients. Hum Reprod Update. 2004;10:251–66.
• Brozovic A, Ambriović-Ristov A, Osmak M. The relationship between cisplatin-induced reactive oxygen species, glutathione, and BCL-2 and resistance to cisplatin. Crit Rev Toxicol. 2010;40:347–59.
• Amin A, Buratovich M. New platinum and ruthenium complexes—the latest class of potential chemotherapeutic drugs-a review of recent developments in the field. Mini Rev Med Chem. 2009;9:1489-503.
• Fung C, Vaughn DJ. Complications associated with chemotherapy in testicular cancer management. Nat Rev Urol. 2011;8:213-22.
• Mohebbati R, Anaeigoudari A, Khazdair MR. The effects of Curcuma longa and curcumin on reproductive systems. Endocr Reg. 2017;51:220-8.
• Aggarwal BB, Harikumar KB. Potential therapeutic effects of curcumin, the anti-inflammatory agent, against neuro degenerative, cardiovascular, pulmonary, metabolic, autoimmune and neoplastic diseases. Int J Biochem Cell Biol. 2009;41:40–59.
• Wang XN, Zhang CJ, Diao HL, Zhang Y. Protective effects of curcumin against sodium arsenite-induced ovarian oxidative injury in a mouse model. Chin Med J. 2017;130:1026-32.
• Wilken R, Veena MS, Wang MB, Srivatsan ES. Curcumin a review of anti-cancer properties and therapeutic activity in head and neck squamous cell carcinoma. Mol Cancer. 2011;10:1-19.
• Mark-Kappeler CJ, Hoyer PB, Devine PJ. Xenobiotic effects on ovarian preantral follicles. Biol Reprod. 2011;85:871–83.
• Atli M, Engin-Ustun Y, Tokmak A, Caydere M, Hucumenoglu S, Topcuoglu C. Dose dependent effect of resveratrol in preventing cisplatin-induced ovarian damage in rats: an experimental study. Reprod Biol. 2017;17:274–80.
• Un H, Ugan RA, Kose D, Bayir Y, Cadirci E, Selli J, Halici Z. A novel effect of aprepitant: protection for cisplatin-induced nephrotoxicity and hepatotoxicity. Eur J. Pharmacol. 2020;880:173168.
• Voznesens’ka T, Bryzhina TM, Sukhina VS, Makohon NV, Aleksieieva IM. Effect of NF-kappaB activation inhibitor curcumin on the oogenesis and follicular cell death in immune ovarian failure in mice. Fiziol Zh. 2010;56:96–101.
• Aktas C, Kanter M, Kocak Z. Antiapoptotic and proliferative activity of curcumin on ovarian follicles in mice exposed to whole body ionizing radiation. Toxicol Indus Health. 2012;28:852–63.
• Rajpert-De Meyts E, Jorgensen N, Graem N, Müller J, CateR L, Skakkebaek NE. Expression of anti-mullerian hormone during normal and pathological gonadal development: association with differentiation of Sertoli and granulosa cells. J Clin Endocrinol Metab. 1999;84:3836-44.
• Tolikas A, Tsakos E, Gerou S, Prapas Y, Loufopoulos A. Anti-mullerian hormone (AMH) levels in serum and follicular fluid as predictors of ovarian response in stimulated (IVF and ICSI) cycles. Hum Fert. 2011;14:246–53.
• Visser JA, de Jong FH, Laven JS, Themmen AP. Anti-mullerian hormone: a new marker for ovarian function. Reproduction. 2006;131:1–9.
• Hansen KR, Knowlton NS, Thyer AC, Charleston JS, Soules MR, Klein NA. A new model of reproductive aging: the decline in ovarian non-growing follicle number from birth to menopause. Hum Reprod. 2008;23:699–708.
• Ibrahim MA, Albahlol IA, Wani FA, Abd-Eltawab Tammam A, Kelleni MT, Sayeed MU, et al. Resveratrol protects against cisplatin-induced ovarian and uterine toxicity in female rats by attenuating oxidative stress, inflammation and apoptosis. Chem Biol Interact. 2021;338:109402.
• Salvioli S, Sikora E, Cooper EL, Franceschi C. Curcumin in cell death processes: a challenge for CAM of age‑related pathologies. Evid Based Comple Alter Med. 2007;4:181‑90.
• Morgan S, Anderson RA, Gourley C, Wallace WH, Spears N. How do chemotherapeutic agents damage the ovary? Hum Reprod Update. 2012;18:525–35.
• Morgan S, Lopes F, Gourley C, Anderson RA, Spears N. Cisplatin and doxorubicin induce distinct mechanisms of ovarian follicle loss; imatinib provides selective protection only against cisplatin. PLoS One. 2013;8:e70117.
• Chang EM, Lim E, Yoon S, Jeong K, Bae S, Lee DR et al. Cisplatin induces overactivation of the dormant primordial follicle through PTEN/AKT/FOXO3a pathway which leads to loss of ovarian reserve in mice. PLoS One. 2015;10:0144245.