Timokinonun izoproterenol ile indüklenen sıçan aortu üzerindeki sitoprotektif etkilerinin değerlendirilmesi

Year 2022, Volume: 47 Issue: 1, 79 - 86, 31.03.2022

Rifat Ozmen Necla Değer Derya Karabulut

https://doi.org/10.17826/cumj.995777

Cited By: 2

Abstract

Amaç: Çalışmada isoproterenol (ISO) kaynaklı aort doku hasarına karşı timokinonun (THQ) sitoprotektif etkilerinin histolojik ve immunohistokimyasal olarak değerlendirilmesi amaçlanmıştır
Gereç ve Yöntem: Sıçanlar dört gruba ayrıldı. (n=8). Kontrol grubu (Kontrol); tedavi uygulanmadı, Timokinon grubu (THQ); 20 mg / kg intragastrik (ig) 8 gün boyunca 24 saat aralıklarla THQ, Isoproterenol grubu (ISO); deneyin 7. ve 8. gününde 100 mg / kg subkutan (sc) ISO (1 ml steril distile suda çözüldü) 24 saat aralıklarla uygulandı. Timokinon+Isoproterenol grubu (THQ+ISO); THQ ig 20 mg/kg 8 gün boyunca ve 100 mg/kg ISO deneyin 7. ve 8. gününde uygulandı. Sıçanların aort dokuları ve kanları alındı. Dokular hematoksilen eozin ve immunohistokimayasal olarak interlökin-6 (IL-6) ve interlökin-17 (IL-17) boyandı. TNF-α, kan serumlarında ELISA ile incelendi.
Bulgular: ISO grubunda aort duvar kalınlığı kontrol ve THQ grubuna kıyasla arttı. Ayrıca bu grupta IL-6 ve IL-17 immunoreaktivitesi de artış gösterdi. IL-17 istatistiksel olarak anlamlıydı. THQ hem duvar kalınlığını hem de IL-6 ve IL-17 ekspresyon seviyelerini düzeltti. TNF-α, ISO grubunda azaldı, fakat gruplar arasında istatistiksel bir farklılık gözlenmedi.
Sonuç: ISO kaynaklı aort doku hasarına karşı THQ sitoprotektif bir ajan olarak hizmet eder.

Keywords

Isoproterenol, timokinon, aort.

Supporting Institution

Erciyes University BAP Unit

Project Number

TYL- 2020-10217

Thanks

Katkılarından dolayı yazarlara teşekkür ederiz.

Evaluation of the cytoprotective effects of thymoquinone on isoproterenol-induced rat aorta

Abstract

Purpose: The aim of this study was to evaluate histologically and immunohistochemically the cytoprotective effects of thymoquinone (THQ) against isoproterenol (ISO)-induced aortic tissue damage.
Materials and Methods: Rats were divided into four groups (n=8). Control group (Control); were untreated rats, Thymoquinone group (THQ); 20 mg / kg intragastrically (ig) THQ at 24 hour intervals for 8 days, Isoproterenol group (ISO); on the 7th and 8th day of the experiment, 100 mg/kg subcutaneous (sc) ISO (dissolved in 1 ml sterile distilled water) was given at 24 hour intervals. Thymoquinone + Isoproterenol group (THQ+ISO); THQ was administered ig at 20 mg/kg for 8 days, and 100 mg/kg ISO was administered on day 7 and day 8 of the experiment. Aortic tissues and blood were collected from rats. Tissues were stained by hematoxylin-eosin and immunohistochemically by interleukin-6 (IL-6) and interleukin-17 (IL-17). TNF-α, ELISA was examined in blood sera.
Results: Aortic wall thickness was found to be increased in the ISO group compared to the control and THQ groups. In addition, IL-6 and IL-17 immunoreactivity increased in this group. IL-17 height was statistically significant. THQ corrected both the increase in wall thickness and the expression levels of IL-6 and IL-17. TNF-α was found to be decreased in the ISO group, but no statistically significant difference was observed between the groups.
Conclusion: THQ serves as a cytoprotective agent

Keywords

Isoproterenol, thymoquinone, aorta.

Project Number

TYL- 2020-10217

References

• Szymanski MW, Singh DP. Isoproterenol. StatPearls. Treasure Island , FL, StatPearls Publishing LLC. 2021.
• Lalitha G, Poornima P, Archanah A, Padma VV. Protective effect of neferine against isoproterenol-induced cardiac toxicity. Cardiovasc Toxicol. 2013;13:168-79.
• Jiang T, Han F, Gao G, Liu M. Mangiferin exert cardioprotective and anti-apoptotic effects in heart failure induced rats. Life Sci. 2020;249:117476.
• Rajadurai M, Prince PS. Preventive effect of naringin on isoproterenol-induced cardiotoxicity in Wistar rats: an in vivo and in vitro study. Toxicology. 2007;232:216-25.
• Matera MG, Page C, Rinaldi B. β2-Adrenoceptor signalling bias in asthma and COPD and the potential impact on the comorbidities associated with these diseases. Curr Opin Pharmacol. 2018;40:142-46.
• Davel AP, Kawamoto EM, Scavone C, Vassallo DV, Rossoni LV. Changes in vascular reactivity following administration of isoproterenol for 1 week: a role for endothelial modulation. Br J Pharmacol. 2006;148:629-39.
• Fleming I, Busse R. Molecular mechanisms involved in the regulation of the endothelial nitric oxide synthase. Am J Physiol Regul Integr Comp Physiol. 2003;284:R1-12.
• Ross R. Atherosclerosis--an inflammatory disease. N Engl J Med. 1999;340:115-26.
• Darakhshan S, Bidmeshki Pour A, Hosseinzadeh Colagar A, Sisakhtnezhad S. Thymoquinone and its therapeutic potentials. Pharmacol Res. 2015;95-96:138-58.
• Khan MA, Tania M, Fu J. Epigenetic role of thymoquinone: impact on cellular mechanism and cancer therapeutics. Drug Discov Today. 2019;24:2315-22.
• Li F, Rajendran P, Sethi G. Thymoquinone inhibits proliferation, induces apoptosis and chemosensitizes human multiple myeloma cells through suppression of signal transducer and activator of transcription 3 activation pathway. Br J Pharmacol. 2010;161:541-54.
• Xu C, Tang F, Lu M, Yang J, Han R, Mei M et al. Astragaloside IV improves the isoproterenol-induced vascular dysfunction via attenuating eNOS uncoupling-mediated oxidative stress and inhibiting ROS-NF-κB pathways. Int Immunopharmacol. 2016;33:119-27.
• Satake N, Shibata M, Shibata S. Endothelium- and cytochrome P-450-dependent relaxation induced by isoproterenol in rat aortic rings. Eur J Pharmacol. 1997;319:37-41.
• Davel AP, Fukuda LE, De Sá LL, Munhoz CD, Scavone C, Sanz-Rosa D et al. Effects of isoproterenol treatment for 7 days on inflammatory mediators in the rat aorta. Am J Physiol Heart Circ Physiol. 2008;295:H211-9.
• Boarescu PM, Chirilă I, Bulboacă AE, Bocșan IC, Pop RM, Gheban D et al. Effects of curcumin nanoparticles in isoproterenol-induced myocardial infarction. Oxid Med Cell Longev. 2019;2019:7847142.
• Khan MS, Gohar A, Abbas G, Mahmood W, Rauf K, Sewell RD. Thymoquinone inhibition of acquisition and expression of alcohol-induced behavioral sensitization. Phytother Res. 2015;29:1610-5.
• Karabulut D, Akin AT, Unsal M, Lekesizcan A, Ozyazgan TM, Keti DB et al. L-Carnitine ameliorates the liver by regulating alpha-SMA, iNOS, HSP90, HIF-1alpha, and RIP1 expressions of CCL4-toxic rats. Iran J Basic Med Sci. 2021;24:184-90.
• Karabulut D, Sonmez MF. Effects of diabetes on nitric oxide synthase in rat uterus. Biotech Histochem. 2020:1-8.
• Karabulut D, Ozturk E, Kuloglu N, Akin AT, Kaymak E, Yakan B. Effects of vitamin B12 on methotrexate hepatotoxicity: evaluation of receptor-interacting protein (RIP) kinase. Naunyn Schmiedebergs Arch Pharmacol. 2020;393:2473-80.
• Clapp BR, Hingorani AD, Kharbanda RK, Mohamed-Ali V, Stephens JW, Vallance P et al. Inflammation-induced endothelial dysfunction involves reduced nitric oxide bioavailability and increased oxidant stress. Cardiovasc Res. 2004;64:172-8.
• Desjardins MP, Sidibé A, Fortier C, Mac-Way F, De Serres S, Larivière R et al. Impact of kidney transplantation on aortic stiffness and aortic stiffness index β0. J Hypertens. 2019;37:1521-28.
• Marais L, Franck G, Allaire E, Zidi M. Diameter and thickness-related variations in mechanical properties of degraded arterial wall in the rat xenograft model. J Biomech. 2016;49:3467-75.
• Cantini C, Kieffer P, Corman B, Limiñana P, Atkinson J, Lartaud-Idjouadiene I. Aminoguanidine and aortic wall mechanics, structure, and composition in aged rats. Hypertension. 2001;38:943-8.
• Cha HN, Hong GR, Kim YW, Kim JY, Dan JM, Park SY. Deficiency of iNOS does not prevent isoproterenol-induced cardiac hypertrophy in mice. Korean J Physiol Pharmacol. 2009;13:153-9.
• Szabó C, Haskó G, Zingarelli B, Németh ZH, Salzman AL, Kvetan V et al. Isoproterenol regulates tumour necrosis factor, interleukin-10, interleukin-6 and nitric oxide production and protects against the development of vascular hyporeactivity in endotoxaemia. Immunology. 1997;90:95-100.
• Feng W, Li W. The study of ISO induced heart failure rat model. Exp Mol Pathol. 2010;88:299-304.
• Madhur MS, Lob HE, McCann LA, Iwakura Y, Blinder Y, Guzik TJ et al. Interleukin 17 promotes angiotensin II-induced hypertension and vascular dysfunction. Hypertension. 2010;55:500-7.
• S M, Shaik AH, E MP, Al Omar SY, Mohammad A, Kodidhela LD. Combined cardio-protective ability of syringic acid and resveratrol against isoproterenol induced cardio-toxicity in rats via attenuating NF-kB and TNF-α pathways. Sci Rep. 2020;10:3426.
• Morimoto K, Kitano T, Eguchi R, Otsuguro K. Bidirectional modulation of TNF-α transcription via α- and β-adrenoceptors in cultured astrocytes from rat spinal cord. Biochem Biophys Res Commun. 2020;528:78-84.
• Viswanadha VP, Dhivya V, Beeraka NM, Huang CY, Gavryushova LV, Minyaeva NN et al. The protective effect of piperine against isoproterenol-induced inflammation in experimental models of myocardial toxicity. Eur J Pharmacol. 2020;885:173524.
• Luan A, Tang F, Yang Y, Lu M, Wang H, Zhang Y. Astragalus polysaccharide attenuates isoproterenol-induced cardiac hypertrophy by regulating TNF-α/PGC-1α signaling mediated energy biosynthesis. Environ Toxicol Pharmacol. 2015;39:1081-90.
• Randhawa MA, Alghamdi MS, Maulik SK. The effect of thymoquinone, an active component of Nigella sativa, on isoproterenol induced myocardial injury. Pak J Pharm Sci. 2013;26:1215-9.
• Ojha S, Azimullah S, Mohanraj R, Sharma C, Yasin J, Arya DS et al. Thymoquinone protects against myocardial ischemic injury by mitigating oxidative stress and inflammation. Evid Based Complement Alternat Med. 2015;2015:143629.
• Ozer EK, Goktas MT, Toker A, Pehlivan S, Bariskaner H, Ugurluoglu C et al. Thymoquinone protects against the sepsis induced mortality, mesenteric hypoperfusion, aortic dysfunction and multiple organ damage in rats. Pharmacol Rep. 2017;69:683-90.
• El-Agamy DS, Nader MA. Attenuation of oxidative stress-induced vascular endothelial dysfunction by thymoquinone. Exp Biol Med (Maywood). 2012;237:1032-8.
• Zhu N, Xiang Y, Zhao X, Cai C, Chen H, Jiang W et al. Thymoquinone suppresses platelet-derived growth factor-BB-induced vascular smooth muscle cell proliferation, migration and neointimal formation. J Cell Mol Med. 2019;23:8482-92.
• Niazmand S, Fereidouni E, Mahmoudabady M, Mousavi SM. Endothelium-independent vasorelaxant effects of hydroalcoholic extract from Nigella sativa seed in rat aorta: the roles of Ca2+ and K+ channels. Biomed Res Int. 2014;2014:247054.
• Karabulut D, Ozturk E, Kaymak E, Akin AT, Yakan B. Thymoquinone attenuates doxorubicin-cardiotoxicity in rats. J Biochem Mol Toxicol. 2021;35:e22618.