Evaluation of Cardiovascular Effects of Carvacrol in a D-(+)-Galactose-Induced aging Model

Sabine Helena Dantas

Programa de Mestrado Profissional em Gerontologia, Centro de Ciências da Saúde, Universidade Federal da Paraíba, João Pessoa, Paraíba, Brazil.

Arthur José Pontes de Almeida

Programa de Pós-graduação em Desenvolvimento e Inovação Tecnológica em Medicamentos, Centro de Ciências da Saúde, Universidade Federal da Paraíba, João Pessoa, Paraíba, Brazil.

Tays Amanda Felisberto Gonçalves

Programa de Pós-graduação em Produtos Naturais e Sintéticos Bioativos, Centro de Ciências da Saúde, Universidade Federal da Paraíba, João Pessoa, Paraíba, Brazil.

Islania Gisélia Albuquerque Araújo

Programa de Mestrado Profissional em Gerontologia, Centro de Ciências da Saúde, Universidade Federal da Paraíba, João Pessoa, Paraíba, Brazil.

Mathania Silva de Almeida Rezende

Programa de Pós-graduação em Produtos Naturais e Sintéticos Bioativos, Centro de Ciências da Saúde, Universidade Federal da Paraíba, João Pessoa, Paraíba, Brazil.

Robson Cavalcante Veras

Programa de Pós-graduação em Produtos Naturais e Sintéticos Bioativos, Centro de Ciências da Saúde, Universidade Federal da Paraíba, João Pessoa, Paraíba, Brazil.

Antônia Lêda Silva

Programa de Mestrado Profissional em Gerontologia, Centro de Ciências da Saúde, Universidade Federal da Paraíba, João Pessoa, Paraíba, Brazil.

Isac Almeida de Medeiros *

Programa de Mestrado Profissional em Gerontologia, Centro de Ciências da Saúde, Universidade Federal da Paraíba, João Pessoa, Paraíba, Brazil and Programa de Pós-graduação em Desenvolvimento e Inovação Tecnológica em Medicamentos, Centro de Ciências da Saúde, Universidade Federal da Paraíba, João Pessoa, Paraíba, Brazil and Programa de Pós-graduação em Produtos Naturais e Sintéticos Bioativos, Centro de Ciências da Saúde, Universidade Federal da Paraíba, João Pessoa, Paraíba, Brazil.

*Author to whom correspondence should be addressed.


Abstract

Aim: To evaluate the cardiovascular effect of carvacrol treatment in a D(+)galactose accelerated aging model, investigating effects on vascular reactivity, oxidative stress, and systolic blood pressure (SBP).

Methodology: Eight-week-old male Wistar rats (Rattus norvegicus) were used for oral treatment for eight weeks. Organ baths were used for vascular reactivity studies (FEN, ACh, and NPS), fluorescence microscopy to detect reactive oxygen species (ROS, using DHE probe), and Tail-Cuff for systolic blood pressure (SBP) measurements. Non-linear regression was used to create the concentration-response curves. Emax denotes the tissue's maximum response.

Results: The aged rats showed a significant increase in fluorescence intensity by the DHE probe compared to the CTL group (CTL=100 ± 3.6%, n=5 and Dgal=167.7 ± 7.9%, n=5, respectively). However, the levels of ROS in the carvacrol-treated groups were significantly attenuated in the Dgal+C50 (138.8 ± 4.5%, n=5) and Dgal+C100 (130.0 ± 5.5%, n=5) groups. The animals of the Dgal group presented hypertension through the significant increase in SBP compared to the CTL group (CTL=135.9 ± 3.9 mmHg, n=6, Dgal=170.9 ± 2.0 mmHg, n=9, respectively). The increased SBP of Dgal rats could be reversed by treatment with carvacrol (Dgal+C50=137.9 ± 2.7 mmHg, n=5, and Dgal+C100=124.6 ± 8.2 mmHg, n=5, respectively. On the other hand, carvacrol was unable to restore the ACh-induced vasorelaxation effect found in CTL (Emax=100.0 ± 3.9%), Dgal (Emax=84.9 ± 4.4%), Dgal+C50 (Emax=84.9 ± 4.4%) and Dgal+C100 (Emax=82.1 ± 6.2 %).

Conclusion: Carvacrol shows protective antioxidant effects capable of reducing SBP in aged animals, being an important tool in promoting healthy aging.

Keywords: Carvacrol, aging, d-galactose-induced aging model, oxidative stress, antioxidant, systolic blood pressure


How to Cite

Dantas, Sabine Helena, Arthur José Pontes de Almeida, Tays Amanda Felisberto Gonçalves, Islania Gisélia Albuquerque Araújo, Mathania Silva de Almeida Rezende, Robson Cavalcante Veras, Antônia Lêda Silva, and Isac Almeida de Medeiros. 2022. “Evaluation of Cardiovascular Effects of Carvacrol in a D-(+)-Galactose-Induced Aging Model”. Journal of Applied Life Sciences International 25 (6):18-27. https://doi.org/10.9734/jalsi/2022/v25i6581.

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References

Aramillo IP, Schauble S, Esser D, Groth M, Frahm C, Priebe S, et al. Transcriptomic alterations during ageing reflect the shift from cancer to degenerative diseases in the elderly. Nature communications. 2018; 9(1):1-11.

Penndorf D, Witte OW, Kretz A. DNA plasticity and damage in amyotrophic lateral sclerosis. Neural regeneration research. 2018;13(2):173-180.

Azman KF, Zakaria R. D-Galactose-induced accelerated aging model: an overview. Biogerontology. 2019;20(6): 763-782.

Xu K, Guo Y, Li Z, Wang Z. Aging biomarkers and novel targets for anti-aging interventions. Reviews on Biomarker Studies in Aging and Anti-Aging Research. 2019b;1178:39-56.

Gude NA, Broughton KM, Firouzi F, Sussman MA. Cardiac ageing: extrinsic and intrinsic factors in cellular renewal and senescence. Nature Reviews Cardiology. 2018;15(9):523-542.

Laina A, Stellos K, Stamatelopoulos K. Vascular ageing: underlying mechanisms and clinical implications. Experimental Gerontology. 2018;109:16-30.

Obas V, Vasan RS. The aging heart. Clinical Science. 2018;132(13): 1367-1382.

Ren J, Zhang Y. Targeting autophagy in aging and aging-related cardiovascular diseases. Trends in Pharmacological Sciences. 2018;39(12):1064-1076.

Chen WK, Tsai YL, Shibu MA, Shen CY, Chang-Lee SN, Chen RJ, et al. Exercise training augments Sirt1-sig- naling and attenuates cardiac inflammation in D-galactose induced-aging rats. Aging. 2018;10(12):4166-4174.

Bo‐Htay C, Palee S, Apaijai N, Chattipakorn SC, Chattipakorn N. Effects of D-galactose-induced ageing on the heart and its potential interventions. Journal of Cellular and Molecular Medicine,2018; 22(3):1392-1410.

Lee J, Kim YS, Kim E, Kim Y, Kim Y. Curcumin and hesperetin attenuate D-galactose-induced brain senescence in vitro and in vivo. Nutrition Research and Practice. 2020;14(5):438-52.

Xu D, Yang J, Yu W, Wei J. Anthocyanins from black chokeberry delayed ageing-related degenerative changes in the heart. Indian J Pharm Educ. 2019a;53(1):112-116.

Fachini-Queiroz FC, Kummer R, Estevão-Silva CF, Carvalho MDB, Cunha JM, Grespan R, et al. Effects of thymol and carvacrol, constituents of Thymus vulgaris L. essential oil, on the inflammatory response. Evidence-Based Complementary and Alternative Medicine. 2012; 2012, 657026.

Riaz S, Shah FA. Pharmacological Investigation of Carvacrol Against D-Galactose-Induced Cognitive Memory Impairment. Molecular Medicine Communications. 2022;2(01):09-20.

Silva ER, Carvalho FO, Teixeira LGB, Santos NGL, Felipe FA, Santana HSR, et al. Pharmacological effects of carvacrol in in Vitro studies: a review. Current pharmaceutical Design. 2018;24(29):3454-3465.

Fritz M, Rinaldi G. Influence of nitric oxide-mediated vasodilation on the blood pressure measured with the tail-cuff method in the rat. Journal of Biomedical Science. 2007;14(6), 757–765.

Assis KS, Araújo IGA, de Azevedo FLAA, Maciel PMP, Machado Calzerra NT, da Silva TAF, Assis VL, de Vasconcelos AP, Santos CAG, Meireles BRLA, Cordeiro AMTM, Araújo DAM, Ribeiro TP, Medeiros IA. Potassium Channel Activation Is Involved in the Cardiovascular Effects Induced by Freeze Dried Syzygium jambolanum (Lam.) DC Fruit Juice. Biomed Res Int. 2018;2018:4827461.

Zhang B, Zhang CG, Zhou QB, Chen W, Wu ZY. Estrogen improves the hyperdynamic circulation and hyporeactivity of mesenteric arteries by alleviating oxidative stress in partial portal vein ligated rats. World J Gastroenterol. 2013;19(40):6863-8

Chang YM, Chang HH, Lin HJ, Tsai CC, Tsai CT, Chang HN, et al. Inhibition of cardiac hypertrophy effects in D-galactose-induced senescent hearts by alpinate oxyphyllae fructus treatment. Evid Based Complement Alternat Med. 2017; 2624384.

Ding AJ, Zheng SQ, Huang XB, Xing TK, Wu GS, Sun HY, et al. Current Perspective in the Discovery of Anti-aging Agents from Natural Products. Natural Products and Bioprospecting. 2017; 7(5):335-404.

Câtanâ C, Atanasov AG, Berindan-Neagoe I. Natural products with anti-aging potential: affected targets and molecular mechanisms. Biotechnology Advances, 2018;36(6):1649 – 1656.

Humphrey JD, Milewicz DM. Aging, Smooth Muscle Vitality, and Aortic Integrity. Circulation Research. 2017;120(12):1849-1851.

Guevara-Balcazar G, Ramirez-Sanchez I, Mera-Jimenez E, Rubio-Gayosso I, Aguilar-Najera ME, Castillo-Hernandez MC. Participation of COX-1 and COX-2 in the contractile effect of phenylephrine in prepubescent and old rats. Korean Journal of Physiology and Pharmacology. 2017; 21(4):407-413.

Favero G, Paganelli C, Buffoli B, Rodella LF, Rezzani R. Endothelium and its alterations in cardiovascular diseases: Life style intervention. BioMed research international. 2014;801896.

Senoner T, Dichtl W. Oxidative stress in cardiovascular diseases: still a terapeutic target?. Nutrients. 2019;11(9):2090.

De A, Ghosh C. Basics of aging theories and disease related aging- an overview. PharmaTutor. 2017;5(2):16-23.

Rizzoni D, Rizzoni M, Nardin M, Chiarini G, Agabiti-Rosei C, Aggiusti C, et al. Vascular aging and disease of the small vessels. High Blood Pressure & Cardiovascular Prevention. 2019;26(3):183-189.

Dai J, Liu R, Zhao J, Zhang A. Sulfur dioxide improves endothelial dysfunction by downregulating the angiotensin II/AT1R pathway in D-galactose-induced aging rats. Journal of the Renin-Angiotensin-Aldosterone System. 2018;19(2): 1470320318778898.

Silva FH, Claudino MA, Calmasini FB, Alexandre EC, Franco-Penteado C, Burnett AL, et al. Sympathetic Hyperactivity, Increased Tyrosine Hydroxylase and Exaggerated Corpus Cavernosum Relaxations Associated with Oxidative Stress Plays a Major Role in the Penis Dysfunction in Townes Sickle Cell Mouse. Plos one. 2016; 11(12):e0166291-e0166291.

Rezende MSA, Almeida AJPO, Gonçalves TAF, Azevedo FLAA, Dantas SH, Silva SL, et al. D-(+)-Galactose-induced aging: A novel experimental model of erectile dysfunction. PLoS One. 2021;16(4): e0249487.

Dehghani, A, Hafizibarjin Z, Najjari R, Kaseb F, Safari F. Resveratrol and 1, 25-dihydroxyvitamin D co-administration protects the heart against D-galactose-induced aging in rats: evaluation of serum and cardiac levels of klotho. Aging clinical and experimental research. 2019; 31(9), 1195-1205.

Wu W, Hou CL, Um XP, Sun C, Zhu YC, Wang MJ,et al. H2S donor NaHS changes the production of endogenous H2S and NO in D-galactose-induced accelerated ageing. Oxidative Med Cell Longev. 2017; 2017:5707830.

Williams B, Mancia G, Spiering W, Rosei EA, Azizi M, Burnier M, et al, ESC Scientific Document Group. 2018 ESC/ESH Guidelines for the management of arterial hypertension. European Heart Journal. 2018;39(33):3021-3104.

Dias CJ, Costa HA, Alves Dias-Filho CA, Ferreira AC, Rodrigues B, Irigoyen MC, Romão Borges AC, de Andadre Martins V, Branco Vidal FC, Ribeiro RM, Filho NS, Mostarda CT. Carvacrol reduces blood pressure, arterial responsiveness and increases expression of MAS receptors in spontaneously hypertensive rats. Eur J Pharmacol. 2022; 917:174717.