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

Dilek Dilli; İrfan Taşoğlu; Eyüp Sarı; Hasan Akduman; Nihat Yumuşak; Naim Boran Tümer; Salih Salar

doi:10.1055/s-0042-1748324

American Journal of Perinatology, Table of Contents

Am J Perinatol 2024; 41(08): 1069-1076
DOI: 10.1055/s-0042-1748324

Original Article

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

Authors

Dilek Dilli

¹Department of Neonatology, University of Health Sciences of Turkey, Dr. Sami Ulus Maternity and Children Training and Research Hospital, Ankara, Turkey
İrfan Taşoğlu

²Department of Cardiovascular Surgery, University of Health Sciences of Turkey, Türkiye Yüksek İhtisas Eğitim ve Araştırma Hastanesi, Ankara City Hospital, Ankara, Turkey
Eyüp Sarı

³Department of Management, Gülhane Faculty of Medicine/Ankara Provincial Health Directorate, University of Health Sciences of Turkey, Public Hospitals Services Presidency, Ankara, Turkey
Hasan Akduman

¹Department of Neonatology, University of Health Sciences of Turkey, Dr. Sami Ulus Maternity and Children Training and Research Hospital, Ankara, Turkey
Nihat Yumuşak

⁴Department of Pathology, Faculty of Veterinary Medicine, Harran University, Şanlıurfa, Turkey
Naim Boran Tümer

²Department of Cardiovascular Surgery, University of Health Sciences of Turkey, Türkiye Yüksek İhtisas Eğitim ve Araştırma Hastanesi, Ankara City Hospital, Ankara, Turkey
Salih Salar

⁵Department of Laboratory, Saki Yenilli Experimental Animals Production Laboratory, Ankara, Turkey

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.

Keywords

antioxidants - aorta - ischemia/reperfusion - rat

Full Text

References

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