Serulein ile Oluşturulmuş Akut Pankreatit Modelinde Astaksantin ve Koenzim Q10’nin Etkisi Sinerjistik Değildir

Öz

 

Amaç: Astaksantin (ATX) ve Koenzim Q10'un (Ubiquinone) çeşitli antiinflamatuvar etkileri farklı inflamasyon modellerinde incelenmiştir. Bu çalışma, sıçan akut pankreatit modelinde astaksantin ve Koenzim Q10'un sinerjistik etkisini araştırmayı amaçlamaktadır.

Gereç ve Yöntem: 24 adet Wistar sıçan; kontrol (C), taşıyıcı  kontrol (AP), astaksantin (ATX; 40 mg / kg), astaksantin + koenzim Q10 (ATX + Q10; ATX+Q10; 40 mg/kg and 1 gr/kg) olarak gruplandırıldı.  Bir saat ara ile iki kez serulein (50 ug / kg) uygulandı. İlk serulein enjeksiyonundan 7 saat sonra sıçanlar öldürüldü. Pankreatik oksidatif hasar, lipaz ve amilazın serum düzeyinde, miyeloperoksidaz aktivitesi (MPO), malondialdehit (MDA), luminol ve lucigenin doku seviyelerinde artışı ve glutatyonın doku seviyesindeki azalması ile değerlendirildi.

Bulgular: Tüm AP gruplarında MDA, MPO artarken GSH azaldı (p <0.001). ATX veya ATX + Q10, artmış MDA ve MPO düzeylerini anlamlı şekilde düşürürken (p <0.001) azalmış GSH düzeyinde artışa neden oldu. (p <0.01) . Her iki tedavi de luminol düzeylerini arttırdı (p <0.001) (p <0.01). Lucigenin Q10 grubunda belirgin olarak azaldı (p <0.01).

Sonuç: Antioksidan kombinasyon tedavisi pankreatik dokudaki oksidatif hasarı tek başına astaksantinden daha iyi hafifletmemektedir.

 

Anahtar Kelimeler

• Astaksantin,Koenzim Q10,oksidatif hasar

Astaxanthin and Coenzyme Q10 are not synergistic against oxidative damage in cerulein-induced acute pancreatitis

Abstract

Background/Aim: The anti-inflammatory effects of Astaxanthin (ATX) and Coenzyme Q10 (Ubiquinone) are studied in different inflammation models. The study aims to investigate the synergistic effect of astaxanthin and Coenzyme Q10 in a rat model of acute pancreatitis. Methods: Twenty-four female Wistar rats were grouped as control (C), carrier-treated control (AP), astaxanthin-treated (ATX; 40 mg/kg), astaxanthin+coenzyme Q10- treated (ATX+Q10; 40 mg/kg and 1 gr/kg) groups. Cerulein was administered (50 µg/kg) twice, one hour apart. Seven hours after the first cerulein injection, the rats were sacrificed. Pancreatic oxidative damage was evaluated with an increase in the serum activity of lipase and amylase, tissue levels of myeloperoxidase activity (MPO), malondialdehyde (MDA), luminol and lucigenin and decrease of glutathione. Results: In all AP groups, MDA and MPO increased while GSH decreased (P<0.001). ATX and ATX+Q10 both decreased MDA and MPO (P<0.001) and increased GSH (P<0.01). Both therapies significantly increased luminol levels (P<0.001, and P<0.01, respectively). Lucigenin markedly decreased in the ATX+Q10 group (P<0.01). Conclusion: Antioxidant combination therapy does not alleviate oxidative damage in pancreatic tissue better than astaxanthin alone.

Keywords

• Astaxanthin
• Coenzyme Q10
• Oxidative Damage
• Acute pancreatitis

Kaynakça

1. 1. Lankisch P, Apte G, Banks P. Acute pancreatitis. The Lancet. 2015;386:85–96.
2. 2. Polotow TG, Vardaris CV, Mihaliuc AR, Gonçalves MS, Pereira B, Ganini D, et al. Astaxanthin supplementation delays physical exhaustion and prevents redox imbalances in plasma and soleus muscles of Wistar rats. Nutrients. 2014;6:5819-38.
3. 3. Greenberg JA, Hsu J, Bawazeer M, et al. Clinical practice guideline: management of acute pancreatitis. Can J Surg. 2016;59(2):128–140.
4. 4. Dervenis C, Johnson CD, Bassi C, et al. Diagnosis, objective assessment of severity, and management of acute pancreatitis. Santorini consensus conference. Int J Pancreatol. 1999;25(3):195–210.
5. 5. Zhang H, Yang W, Li Y, Hu L, Dai Y, Chen J, et al. Astaxanthin ameliorates cerulein-induced acute pancreatitis in mice. Int. Immunopharmacol. 2018;56:18-28.
6. 6. Siriwardena AK, Mason JM, Balachandra S, Bagul A, Galloway S, Formela Let al. Randomised, double blind, placebo controlled trial of intravenous antioxidant (n-acetylcysteine, selenium, vitamin C) therapy in severe acute pancreatitis. Gut. 2007;56:1439-44.
7. 7. Ambati RR, Phang SM, Ravi S, et al. Astaxanthin: sources, extraction, stability, biological activities and its commercial applications – a review. Mar Drugs. 2014;12:128.
8. 8. Naguib YMA. Antioxidant Activities of Astaxanthin and Related Carotenoids. Journal of Agricultural and Food Chemistry. 2000;48(4):1150–4.

9. 9. Miki, W. Biological functions and activities of animal carotenoids. Pure Appl. Chem. 1991;63:141-6.
10. 10. Chang CS, Chang CL, Lai GH. Reactive oxygen species scavenging activities in a chemiluminescence model and neuroprotection in rat pheochromocytoma cells by astaxanthin, beta-carotene, and canthaxanthin. Kaohsiung J Med. Sci. 2013;29:412-21.
11. 11. Santocono M, Zurria M, Berrettini M, Fedeli D, Falcioni G. Influence of astaxanthin, zeaxanthin and lutein on DNA damage and repair in UVA-irradiated cells. J. Photochem. Photobiol B. 2006;85:205-15.
12. 12. Nohl H, Gille L, Staniek K. The biochemical, pathophysiological, and medical aspects of ubiquinone function. Ann. NY Acad. Sci. 1998;854:394–409.
13. 13. Lonnrot K, Metsa-Ketela T, Molnar G, Ahonen JP, Latvala M, Peltola J, Pietila T, Alho H. The effect of ascorbate and ubiquinone supplementation on plasma and CSF total antioxidant capacity. Free Radic Biol Med. 1996;21:211–7.
14. 14. Damia MS, Ellenberg D, Gildemeister R, Lauermann J, Simonis G, Sauter W, Georgi C. Coenzyme Q10 combined with mild hypothermia after cardiac arrest: a preliminary study. Circulation. 2004;110:3011–16.
15. 15. Lockwood K, Moesgaard S, Yamamoto T, Folkers K. Progress on therapy of breast cancer with vitamin Q10 and the regression of metastases. Biochem Biophys Res Commun. 1995;212:172–7.
16. 16. Honda K, Saneyasu T, Motokı T, Park Y, Kamısoyama H. Dietary Coenzyme Q10 Suppressed Hepatic Hydroxymethylglutaryl-CoA Reductase Activity in Laying Hens. Bioscience Biotechnology and Biochemistry. 2013;77:1572-4.
17. 17. Casini A, Ferrali M, Pompella AS, Maellaro E, Comporti M. Lipid peroxidation and cellular damage in extrahepatic tissues of bromobenzene-intoxicated mice. Am J Pathol. 1986;123:520–31.
18. 18. Beutler E, Glutathione in Red Blood Cell Metabolism A Manual of Biochemical Methods, Grune & Stratton, New York, 1975,112–114.
19. 19. Bradley, Priebat D, Christensen R. Rothstein G. Measurement of cutaneous inflammation: estimation of neutrophil content with an enzyme marker. J. Invest Dermatol. 1982;78:206–9.
20. 20. Kikuchi K. Nagano H, Hayakawa Y, Hirata M. Detection of nitric oxide production from a perfused organ by a luminol-H2O2 system. Anal Chem. 1993;65:1794–9.
21. 21. Yadav D, Lowenfels AB. The epidemiology of pancreatitis and pancreatic cancer. Gastroenterology. 2013 Jun;144(6):1252-61.
22. 22. Mirmalek SA, Gholamrezaei Boushehrinejad A, Yavari H, Kardeh B, Parsa Y, Salimi-Tabatabaee SA, et al. Antioxidant and Anti-Inflammatory Effects of Coenzyme Q10 on L-Arginine-Induced Acute Pancreatitis in Rat. Oxid Med Cell Longev. 2016;2016:5818479.
23. 23. Moreno C, Nicaise C., Gustot T, Quertinmont E, Nagy N, Parmentier M, et al. Chemokine receptor CCR5 deficiency exacerbates cerulein-induced acute pancreatitis in mice.Am. J. Physiol. 2006;291:1089–99.
24. 24. Taylor HR, Tikellis G, Robman LD, McCarty CA, and McNeil JJ. Vitamin E supplementation and macular degeneration: randomized controlled trial. Brit Med J. 2002;325:7354:11.
25. 25. Moller P, Vogel U, Pederson A, Dragsted L O, Sandstrom B and Loft S. No effect of 600 grams fruit and vegetables per day on oxidative DNA damage and repair in healthy nonsmokers. Cancer Epidemiol. Biomarkers Pre V. 2003;2:1016–22.
26. 26. Yanai N Shiotani S, Hagiwara S, Nabetani H & Nakajima M. Antioxidant Combination Inhibits Reactive Oxygen Species Mediated Damage. Bioscience, Biotechnology, and Biochemistry. 2008;72:12:3100-6.
27. 27. Zhang Z, Xu X, Liu T, Yuan S. Mitochondrion-Permeable Antioxidants to Treat ROS-Burst-Mediated Acute Diseases. Oxid Med Cell Longev. 2016;6859523.
28. 28. Bolin AP, Macedo RC, Marin DP, Barros MP, Otton R. Astaxanthin prevents in vitro auto-oxidative injury in humanlymphocytes. Cell Biology and Toxicology. 2010;26(5):457-67.
29. 29. Singh U, Devaraj S, Jialal I. Coenzyme Q10 supplementation and heart failure. Nutrition Reviews. 2007;65:6:286–93.
30. 30. Sandor PS, DiClemente L, Coppolaetal G. Efficacy of coenzyme Q10 in migraine prophylaxis: a randomized controlled trial. Neurology. 2005;64:4:71–5.
31. 31. Rosenfeldt FL, Haas SJ, Krumetal H. CoenzymeQ10 in the treatment of hypertension: a meta-analysis of the clinical trials. Journal of Human Hypertension. 2007;21:4:297–306.
32. 32. Mancuso M, Orsucci D, Volpi L, Calsolaro V, Siciliano G. Coenzyme Q10 in neuromuscular and neurodegenerative disorders. Current Drug Targets. 2010;11:1:111–21.
33. 33. Sutachan JJ, Casas Z, Albarracin ZL, et al. Cellular and molecular mechanisms of antioxidants in Parkinson’s disease. Nutritional Neuroscience. 2012:15:3:120–6.
34. 34. Kardeh S, Ashkani S, Esfahani S, Alizadeh AM. Paradoxicalaction of reactive oxygen species increation and therapy of cancer. European Journal of Pharmacology. 2014; 735:1:150–68.
35. 35. Traber MG, Stevens JF. Vitamins C and E: beneficial effects from a mechanistic perspective. Free Radical Biology and Medicine. 2011;51:5:1000–13.
36. 36. Guleken Z, Ozbeyli D, Acikel-Elmas M, Oktay S, Alev B, Sirvanci S, et al. The effect of estrogen receptor agonists on pancreaticobiliary duct ligation induced experimental acute pancreatitis. J. Physiol. Pharmacol. 2017;68:847-58.
37. 37. Dokumacioglu E., Iskender H, Yenice G, Kapakin KAT, Sevim C, Hayirli A, et al. Effects of astaxanthin on biochemical and histopathological parameters related to oxidative stress on testes of rats on high fructose regime. Andrologia. 2018;50:e13042.
38. 38. Kim H. Cerulein pancreatitis: oxidative stress, inflammation, and apoptosis. Gut Liver. 2008;2(2):74–80.
39. 39. Gómez-Cambronero L, Camps B, de La Asunción JG, Cerdá M, Pellín A, Pallardó FV, et al. Pentoxifylline ameliorates cerulein-induced pancreatitis in rats: role of glutathione and nitric oxide. J Pharmacol Exp Ther. 2000 May;293(2):670-6.
40. 40. Fındık H, Tumkaya L, Yılmaz A, Gökhan Aslan M, Okutucu M, Akyildiz K, et al. The protective effects of astaxanthin against cisplatin-induced retinal toxicity. Cutaneous Ocul Toxicol. 2019;38:59-65.