Am J Perinatol
DOI: 10.1055/s-0042-1748324
Original Article

Therapeutic Role of Astaxanthin and Resveratrol in an Experimental Rat Model of Supraceliac Aortic Ischemia-Reperfusion

1   Department of Neonatology, University of Health Sciences of Turkey, Dr. Sami Ulus Maternity and Children Training and Research Hospital, Ankara, Turkey
,
İrfan Taşoğlu
2   Department of Cardiovascular Surgery, University of Health Sciences of Turkey, Türkiye Yüksek İhtisas Eğitim ve Araştırma Hastanesi, Ankara City Hospital, Ankara, Turkey
,
Eyüp Sarı
3   Department of Management, Gülhane Faculty of Medicine/Ankara Provincial Health Directorate, University of Health Sciences of Turkey, Public Hospitals Services Presidency, Ankara, Turkey
,
Hasan Akduman
1   Department of Neonatology, University of Health Sciences of Turkey, Dr. Sami Ulus Maternity and Children Training and Research Hospital, Ankara, Turkey
,
Nihat Yumuşak
4   Department of Pathology, Faculty of Veterinary Medicine, Harran University, Şanlıurfa, Turkey
,
Naim Boran Tümer
2   Department of Cardiovascular Surgery, University of Health Sciences of Turkey, Türkiye Yüksek İhtisas Eğitim ve Araştırma Hastanesi, Ankara City Hospital, Ankara, Turkey
,
Salih Salar
5   Department of Laboratory, Saki Yenilli Experimental Animals Production Laboratory, Ankara, Turkey
› Author Affiliations
Funding Information This project was supported by the Scientific Research Projects (BAP) Commission of Health Sciences University of Turkey (Research project no: 2020/060). We declare that the funders did not have a role in the study design, data collection, and analysis, decision to publish, or preparation of the manuscript.

Abstract

Objective The aim of the study is to investigate the therapeutic effects of astaxanthin (AST) and resveratrol (RVT) on multiorgan damage in an animal model of the supraceliac aortic ischemia-reperfusion (I/R).

Methods In this study, 28 rats (n = 7/group), 200 to 250 g in weight, were randomized to four groups (1: Sham, 2: Control + I/R, 3: AST + I/R, and 4: RVT + I/R). Following the abdominal incision, aortic dissection was performed in the sham group without injury. Other groups underwent I/R injury via supraceliac aortic clamping (20 minutes) and reperfusion. The rats were administered olive oil (3 mL/kg) orally for 2 weeks before and 1 week after the laparotomy. Additionally, oral AST (10 mg/kg) or RVT (50 mg/kg) was given to the study groups. All rats were sacrificed on the 3rd week of the experiment after blood samples were taken for analysis. Multiple rat tissues were removed.

Results We found that RVT increased total antioxidant status (TAS) and superoxide dismutase (SOD) levels, and decreased total oxidant status (TOS), oxidative stress index (OSI), myeloperoxidase (MPO), and malondialdehyde (MDA) levels, while AST increased the levels of TAS, decreased TNF-α, MDA, TOS, and OSI (p <0.05). Pathological investigations of the rat tissues revealed that both AST and RVT ameliorated tissue damage and apoptosis.

Conclusion Our study suggests that AST and RVT might show therapeutic effects against oxidative tissue damage and apoptosis in an animal model of aortic I/R. Further studies are required.

Key Points

  • Major congenital heart diseases are at high risk of multiorgan damage.

  • Re-establishment of blood flow may result in ischemia-reperfusion (I/R) injury.

  • Astaxanthin and resveratrol may have therapeutic effects against I/R injury.

Authors' Contributions

D.D. did the data curation, formal analysis, resources, software, writing-original draft, writing-review and editing. İ.T. contributed toward data curation, formal analysis, investigation, methodology, resources, writing-original draft, writing-review and editing. E.S. did the conceptualization, resources, validation, writing-review and editing. H.A. did the formal analysis, investigation, methodology, resources, software, validation, writing-original draft, writing-review and editing. N.Y. did the formal analysis, investigation, methodology, resources, software, validation, visualization, writing-original draft. N.B.T. contributed toward conceptualization, data curation, formal analysis, investigation, methodology, project administration, resources, software, supervision, validation, visualization, writing-original draft, writing-review and editing. S.S. did the formal analysis, investigation, methodology, resources, software, supervision, validation, visualization, writing-original draft.




Publication History

Received: 02 January 2022

Accepted: 28 February 2022

Article published online:
29 May 2022

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  • References

  • 1 Chang RK, Gurvitz M, Rodriguez S. Missed diagnosis of critical congenital heart disease. Arch Pediatr Adolesc Med 2008; 162 (10) 969-974
  • 2 Krishna MR, Kumar RK. Diagnosis and management of critical congenital heart diseases in the newborn. Indian J Pediatr 2020; 87 (05) 365-371
  • 3 Nichols DG, Ungerleider RM, Spevak PJ. et al. Critical Heart Disease in Infants and Children 2nd ed. Mosby;. 2006
  • 4 Ceyran H, Narin F, Narin N. et al. The effect of high dose melatonin on cardiac ischemia-reperfusion Injury. Yonsei Med J 2008; 49 (05) 735-741
  • 5 Bhat VB, Madyastha KM. Scavenging of peroxynitrite by phycocyanin and phycocyanobilin from Spirulina platensis: protection against oxidative damage to DNA. Biochem Biophys Res Commun 2001; 285 (02) 262-266
  • 6 Fu YQ, Hua C, Zhou J, Cheng BR, Zhang J. Protective effects of ginseng total saponins against hepatic ischemia/reperfusion injury in experimental obstructive jaundice rats. Pharm Biol 2013; 51 (12) 1545-1551
  • 7 Zweier JL, Talukder MA. The role of oxidants and free radicals in reperfusion injury. Cardiovasc Res 2006; 70 (02) 181-190
  • 8 Brown DR, Gough LA, Deb SK, Sparks SA, McNaughton LR. Astaxanthin in Exercise Metabolism, Performance and Recovery: a review. Front Nutr 2018; 4: 76
  • 9 Higuera-Ciapara I, Félix-Valenzuela L, Goycoolea FM. Astaxanthin: a review of its chemistry and applications. Crit Rev Food Sci Nutr 2006; 46 (02) 185-196
  • 10 Kogure K. Novel antioxidative activity of astaxanthin and its synergistic effect with vitamin E. J Nutr Sci Vitaminol (Tokyo) 2019; 65 (suppl): S109-S112
  • 11 Ambati RR, Phang SM, Ravi S, Aswathanarayana RG. Astaxanthin: sources, extraction, stability, biological activities and its commercial applications—a review. Mar Drugs 2014; 12 (01) 128-152
  • 12 Aoi W, Naito Y, Sakuma K. et al. Astaxanthin limits exercise-induced skeletal and cardiac muscle damage in mice. Antioxid Redox Signal 2003; 5 (01) 139-144
  • 13 Li W, Hellsten A, Jacobsson LS, Blomqvist HM, Olsson AG, Yuan XM. Alpha-tocopherol and astaxanthin decrease macrophage infiltration, apoptosis and vulnerability in atheroma of hyperlipidaemic rabbits. J Mol Cell Cardiol 2004; 37 (05) 969-978
  • 14 Lauver DA, Lockwood SF, Lucchesi BR. Disodium disuccinate astaxanthin (Cardax) attenuates complement activation and reduces myocardial injury following ischemia/reperfusion. J Pharmacol Exp Ther 2005; 314 (02) 686-692
  • 15 Wang B, Yang Q, Sun YY. et al. Resveratrol-enhanced autophagic flux ameliorates myocardial oxidative stress injury in diabetic mice. J Cell Mol Med 2014; 18 (08) 1599-1611
  • 16 Yang L, Zhang Y, Zhu M. et al. Resveratrol attenuates myocardial ischemia/reperfusion injury through up-regulation of vascular endothelial growth factor B. Free Radic Biol Med 2016; 101: 1-9
  • 17 Wu JM, Wang ZR, Hsieh TC, Bruder JL, Zou JG, Huang YZ. Mechanism of cardioprotection by resveratrol, a phenolic antioxidant present in red wine (review). Int J Mol Med 2001; 8 (01) 3-17
  • 18 Maulik N. Reactive oxygen species drives myocardial angiogenesis?. Antioxid Redox Signal 2006; 8 (11-12): 2161-2168
  • 19 Hung LM, Chen JK, Huang SS, Lee RS, Su MJ. Cardioprotective effect of resveratrol, a natural antioxidant derived from grapes. Cardiovasc Res 2000; 47 (03) 549-555
  • 20 Bakan N, Taysi S, Yilmaz O. et al. Glutathione peroxidase, glutathione reductase, Cu-Zn superoxide dismutase activities, glutathione, nitric oxide, and malondialdehyde concentrations in serum of patients with chronic lymphocytic leukemia. Clin Chim Acta 2003; 338 (1-2): 143-149
  • 21 Erel O. A new automated colorimetric method for measuring total oxidant status. Clin Biochem 2005; 38 (12) 1103-1111
  • 22 Erel O. A novel automated direct measurement method for total antioxidant capacity using a new generation, more stable ABTS radical cation. Clin Biochem 2004; 37 (04) 277-285
  • 23 Sun AY, Chen YM, James-Kracke M, Wixom P, Cheng Y. Ethanol-induced cell death by lipid peroxidation in PC12 cells. Neurochem Res 1997; 22 (10) 1187-1192
  • 24 Bradley PP, Priebat DA, Christensen RD, Rothstein G. Measurement of cutaneous inflammation: estimation of neutrophil content with an enzyme marker. J Invest Dermatol 1982; 78 (03) 206-209
  • 25 Owumi SE, Aliyu-Banjo NO, Danso OF. Fluoride and diethylnitrosamine coexposure enhances oxido-inflammatory responses and caspase-3 activation in liver and kidney of adult rats. J Biochem Mol Toxicol 2019; 33 (07) e22327
  • 26 Owumi SE, Dim UJ. Manganese suppresses oxidative stress, inflammation and caspase-3 activation in rats exposed to chlorpyrifos. Toxicol Rep 2019; 6: 202-209
  • 27 He F, Wu Q, Xu B. et al. Suppression of Stim1 reduced intracellular calcium concentration and attenuated hypoxia/reoxygenation induced apoptosis in H9C2 cells. Biosci Rep 2017; 37 (06) BSR20171249
  • 28 Xing D, Zhang R, Li S. et al. Pivotal role of mast cell carboxypeptidase A in mediating protection against small intestinal ischemia-reperfusion injury in rats after ischemic preconditioning. J Surg Res 2014; 192 (01) 177-186
  • 29 Hausenloy DJ, Yellon DM. Ischaemic conditioning and reperfusion injury. Nat Rev Cardiol 2016; 13: 193-209
  • 30 Endesfelder S, Strauß E, Scheuer T, Schmitz T, Bührer C. Antioxidative effects of caffeine in a hyperoxia-based rat model of bronchopulmonary dysplasia. Respir Res 2019; 20 (01) 88
  • 31 Nishida Y, Yamashita E, Miki W. Quenching activities of common hydrophilic and lipophilic antioxidants against singlet oxygen using chemiluminescence detection system. Carotenoid Sci 2007; 11: 16-20
  • 32 Durukan Y, Bala MM, Şahin AA, Fırat T, Buğdaycı G, Özturan KE. The effect of astaxanthine on ischemia-reperfusion injury in a rat model. J Orthop Sci 2021 Aug 9:S0949-2658(21)00201-3
  • 33 Choi HD, Kim JH, Chang MJ, Kyu-Youn Y, Shin WG. Effects of astaxanthin on oxidative stress in overweight and obese adults. Phytother Res 2011; 25 (12) 1813-1818
  • 34 Islam MA, Al Mamun MA, Faruk M. et al. Astaxanthin ameliorates hepatic damage and oxidative stress in carbon tetrachloride-administered rats. Pharmacognosy Res 2017; 9 (Suppl. 01) S84-S91
  • 35 Nasiri M, Ahmadizad S, Hedayati M, Zarekar T, Seydyousefi M, Faghfoori Z. Trans-resveratrol supplement lowers lipid peroxidation responses of exercise in male Wistar rats. Int J Vitam Nutr Res 2021; 91 (5-6): 507-512
  • 36 Xiang M, Lu Y, Xin L. et al. Role of oxidative stress in reperfusion following myocardial ischemia and its treatments. Oxid Med Cell Longev 2021; 2021: 6614009
  • 37 Otton R, Marin DP, Bolin AP. et al. Astaxanthin ameliorates the redox imbalance in lymphocytes of experimental diabetic rats. Chem Biol Interact 2010; 186 (03) 306-315
  • 38 Yu D, Xiong J, Gao Y. et al. Resveratrol activates PI3K/AKT to reduce myocardial cell apoptosis and mitochondrial oxidative damage caused by myocardial ischemia/reperfusion injury. Acta Histochem 2021; 123 (05) 151739