ÇalıĢmamızda spirulinanın akut ve kronik yüzme egzersizine bağlı oksidatif stres ve antioksidan savunmaya ve akut tüketici egzersizi devam ettirebilme kapasitesine etkileri değerlendirildi. Bu çalıĢma ile egzersize bağlı oksidatif strese karĢı koruyucu olarak spirulinanın potansiyel etkilerinin araĢtırılması amaçlandı.
ÇalıĢmamızda spirulinanın oksidatif strese ve dayanıklılık süresine etkisini değerlendirmek için 48 adet Wistar albino soyunda sıçan kullanıldı. Deneysel model olarak sıçanı tercih ettik, çünkü bu model (insan çalıĢmalarına nazaran) deneysel Ģartların daha titiz standardize edilmesine ve karaciğer ve kas dokularında analiz yapılmasına izin veriyordu. Elde ettiğimiz bulgulara göre, spirulina takviyesinin sıçanların vücut ağırlığına ve tükenme egzersizi süresine etki etmediği gözlendi. Uyguladığımız kronik egzersiz modeli bazı antioksidan biyobelirteçlerinde artıĢa, oksidatif stres biyobelirteçlerinde ise azalmaya yol açtı. Tükenme egzersizi özellikle plazma biyokimyasal belirteçlerde önemli oranda artıĢa yol açarken spirulina takviyesi bu artıĢı düzeltti.
Sonuç olarak, çalıĢmamızdan elde ettiğimiz verilere göre spirulina takviyesinin plazmadaki bazı biyokimyasal belirteçlerde düzelmeye yol açtığı, ancak gerek plazmada gerekse karaciğer ve iskelet kası dokularında oksidatif strese ve antioksidan duruma etkisinin çeliĢkili olduğu gözlendi. Bununla birlikte, daha detaylı ve yeni biyobelirteçler kullanılarak spirulinanın egzersize bağlı oksidatif strese etkinliğinin tespit edilmesi gerektiği sonucuna ulaĢılmıĢtır.
55
6. ÖZET
T.C. SELÇUK ÜNĠVERSĠTESĠ
SAĞLIK BĠLĠMLERĠ ENSTĠTÜSÜ
Sıçanlarda Spirulina Desteğinin Egzersize Bağlı Oksidatif Hasara ve Dayanıklılık Kapasitesine Etkileri
Mehmet ÖZ
Fizyoloji (TIP) Anabilim Dalı
DOKTORA TEZĠ/ KONYA-2013
Bu çalıĢma, spirulinanın akut ve kronik yüzme egzersizine bağlı oksidatif stres ve antioksidan savunmaya ve akut tüketici egzersizi devam ettirebilme kapasitesine etkilerini değerlendirmek amacıyla yapıldı.
ÇalıĢmada 48 adet Wistar soyunda ve 352±27 g ağırlığında eriĢkin erkek sıçan kullanıldı. Tüm sıçanlar rastgele seçimle her grupta 8 sıçan olacak Ģekilde 6 gruba bölündü. Kontrol (KON) grubu çeĢme suyu aldı. Spirulina (SP) grubu 6 hafta süresince her gün oral yolla 750 mg/kg spirulina aldı. Kronik Egzersiz (KE) grubuna haftada 5 gün, günde bir saat olmak üzere 6 hafta boyunca yüzme egzersizi yaptırıldı. Kronik Egzersiz + Spirulina (KES) grubuna kronik egzersiz yaptırıldı ve spirulina verildi. Tükenme Egzersizi (T) grubu tükeninceye kadar yüzdürüldü. Tükenme Egzersizi + Spirulina (TS) grubu 6 haftalık spirulina takviyesi sonrası tükeninceye kadar yüzdürüldü. ÇalıĢma sonunda T ve TS grupları egzersizden hemen sonra, diğer gruplar son egzersiz oturumundan 24 saat sonra sakrifiye edildi. Plazma, karaciğer ve iskelet kası dokusu toplandı. Plazmada kreatin kinaz (CK), kreatin kinaz MB, laktat dehidrogenaz ve ürik asit, tüm örneklerden malondialdehit (MDA), miyeloperoksidaz, ksantin oksidaz (XO), süperoksit dismutaz (SOD), katalaz, glutatyon peroksidaz ve antioksidan aktivite tayinleri yapıldı.
Spirulina takviyesi sonrası sıçanların vücut ağırlığında gözlenen değiĢiklikler anlamlı değildi. Tükenme süreleri açısından T ve TS grupları arasında fark bulunamadı. Spirulina takviyesi tükenme egzersizine bağlı plazma CK aktivitesinde meydana gelen artıĢta düzelmeye yol açtı. Kronik egzersiz plazma SOD aktivitesinde artma meydana getirirken karaciğer dokusu XO, MDA ve kas dokusu MDA seviyesinde azalmaya yol açtı. Tükenme egzersizi karaciğer CAT aktivitesinde azalmaya yol açarken plazma CAT aktivitesinin arttığı gözlendi.
Spirulina takviyesinin plazma biyokimyasal belirteçlerinde iyileĢmeye yol açtığı, ancak gerek plazmada gerekse karaciğer ve iskelet kası dokularındaki oksidatif strese ve antioksidan duruma etkisinin çeliĢkili olduğu gözlendi. Elde edilen bulguların ıĢığında, spirulinanın egzersize bağlı oksidatif strese etkinliğinin daha detaylı ve yeni biyobelirteçler kullanılarak tespit edilmesi gerektiği sonucuna ulaĢıldı.
56
7. SUMMARY
Effects of Spirulina Supplementation on Exercise-Induced Oxidative Damage and Endurance Capacity in Rats
Mehmet ÖZ
Physiology (Medicine)
PhD Thesis / KONYA-2013
This study was aimed to evaluate the effects of spirulina on oxidative stress caused by acute and chronic swimming exercises on anti-oxidant defense and the ability to continue acute exhaustive exercise.
Adult 48 Wistar male rats weighing 352±27 g were used in the study. All the rats were divided randomly into 6 groups, each with 8 rats. The control group (CON) was given tap water. Spirulina (SP) group, on the other hand, was administered 750 mg/kg spirulina orally every day for 6 weeks. The chronic exercise group (CE) was submitted to swimming exercise for 6 weeks, 5 days a week and an hour a day. The Chronic Exercise + Spirulina (CES) group was submitted to chronic exercise and received spirulina. The exhaustive exercise group (T) was submitted to swimming until they were exhausted. Exhaustive Exercise + Spirulina (TS) group was submitted to swimming until they were exhausted after a 6-week spirulina supplementation. At the end of the study, T and TS groups were sacrificed right after the exercise whereas the other groups were sacrificed 24 hours after the last exercise session. Plasma, liver and skeletal muscle tissues were collected. Creatine kinase (CK), creatine kinase MB, lactate dehydrogenase and uric acid activities were determined in the plasma whereas in all the samples, malondialdehyde (MDA), myeloperoxidase, xhantine oxidase, superoxide dismutase, catalase, glutathione peroxidase and antioxidant activities were identified.
The changes that were observed in the body weights of the rats as a result of Spirulina supplementation were not significant. There were no differences between T and TS groups in terms of exhaustion time. Spirulina addition led to a correction in the increase that occurred in plasma CK activity due to exhaustion exercise. While chronic exercise caused an increase in plasma SOD activity, it led to a decrease in liver tissue XO, MDA levels and muscle tissue MDA levels. Exhaustion exercise led to a reduction in liver CAT activity but plasma CAT activity increased.
It was observed that spirulina supplement led to an improvement in plasma biochemical markers but that its effect on oxidative stress and antioxidant state in both plasma and in liver and skeletal muscle tissues were contradictory. However, it was concluded, as a result of the data that were obtained, that spirulina’s effect on exercise-induced oxidative stress need to be determined using more detailed and new biomarkers.
57
8. KAYNAKLAR
1. AkkuĢ Ġ. Serbest radikaller ve fizyopatolojik etkileri. Konya: Mimoza yayınları, 1995:1-73.
2. Alderton WK, Cooper CE, Knowles RG. Nitric oxide synthases: structure, function and inhibition.
Biochem J 2001;357:593-615.
3. Alessio HM, Hagerman AE, Fulkerson BK, Ambrose J, Rice RE, Wiley RL. Generation of reactive
oxygen species after exhaustive aerobic and isometric exercise. Med Sci Sports Exerc. 2000;32(9):1576-81.
4. Altan N, Dinçel AS, Koca C. Diabetes mellitus and oxidative stress. Turk J Biochem. 2006;
31(2):51–56.
5. Aslan R, Dündar Y. Nitric oxide as biophysiological companent and a radical metabolite. Konya
Hayvancılık AraĢ Derg 1998;8:34-38.
6. Auroma O. Free radicals, antioxidants and international nutrition review. Asia Pacific J Clin Nutr.
1999;8:53-63.
7. Aydin C, Sonat F, Sahin SK, Cangul IT, Ozkaya G. Long term dietary restriction ameliorates
swimming exercise-induced oxidative stress in brain and lung of middle-aged rat. Indian J Exp Biol. 2009;47(1):24-31.
8. Baicus C, Baicus A. Spirulina did not ameliorate idiopathic chronic fatigue in four N-of-1
randomized controlled trials.Phytother Res. 2007;21(6):570-3.
9. Baykal Y, Gök F, Erikçi S. Demir, serbest radikaller ve oksidatif hasar. Sendrom 2002;14(1):94-
100.
10. Becker EW, Jakober B, Luft D, et al. Clinical and biochemical evaluations of the alga Spirulina
with regard to its application in the treatment of obesity. A double-blind cross-over study. Nutr Rep Int. 1986;33:565-574.
11. Bhat VB, Madyastha KM. C-phycocyanin: a potent peroxyl radical scavenger in vivo and in vitro.
Biochem Biophys Res Commun. 2000;275(1):20-5.
12. Blinkova LP, Gorobets OB, Baturo AP. Biological avtivity of spirulina. Zh Mikrobiol Epidemiol
Immunobiol. 2001;(2):114-18.
13. Bloomer RJ, Goldfarb AH, Wideman L, McKenzie MJ, Consitt LA. Effects of acute aerobic and
anaerobic exercise on blood markers of oxidative stress. J Strength Cond Res. 2005;19(2):276- 85.
14. Bloomer RJ. Effect of exercise on oxidative stress biomarkers. Adv Clin Chem 2008;46:1-50.
15. Braughler JM, Hall ED. Central nervous system trauma and stroke. I. Biochemical considerations
for oxygen radical formation and lipit peroxidation.Free Radic Biol Med. 1989;6(3):289-301.
16. Brigelius-Flohe R. Tissue-specific functions of individual glutathione peroxidases. Free Radic
Biol Med. 1999;27:951–65.
17. Bucioli SA, de Abreu LC, Valenti VE, Leone C, Vannucchi H. Effects of vitamin E
supplementation on renal non-enzymatic antioxidants in young rats submitted to exhaustive exercise stress. BMC Complement Altern Med. 2011;20;11:133.
18. Burton GW, Ingold KU. Vitamin E as an in vitro and in vivo antioxidant. Ann N Y Acad Sci. 1989;570:7-22.
58
19. Cadenas E.Basic mechanisms of antioxidant activity.Biofactors. 1997;6(4):391-7.
20. Caillaud C, Py G, Eydoux N, Legros P, Prefaut C, Mercier J. Antioxidants and mitochondrial
respiration in lung, diaphragm, and locomotor muscles: effect of exercise. Free Radic Biol Med. 1999;26(9-10):1292-9.
21. Campanella L, Russo MV, Avino P. Free and total amino acid composition in blue-green algae.
Ann Chim. 2002;92(4):343-52.
22. Cao X, Antonyuk SV, Seetharaman SV, Whitson LJ, Taylor AB, Holloway SP. Structures of the
G85R variant of SOD1 in familial amyotrophic lateral sclerosis. J Biol Chem. 2008;283:16169–77.
23. Chae CH, Shin CH, Kim HT. The combination of alpha-lipoic acid supplementation and aerobic
exercise inhibits lipit peroxidation in rat skeletal muscles. Nutr Res. 2008;28(6):399-405.
24. Chandan K. SEN, Handbook of oxidants and antioxidants in exercise. Elsevier Science B.V. All
rights reserved 2000.
25. Cheeseman KH, Slater TF. An introduction to free radical biochemistry. Br Med Bull.
1993;49(3):481-93.
26. Chelikani P, Fita I, Loewen PC. Diversity of structures and properties among catalases. Cell Mol
Life Sci. 2004;61:192–208.
27. Cheong SH, Kim MY, Sok DE, Hwang SY, Kim JH, Kim HR, Lee JH, Kim YB, Kim MR.
Spirulina prevents atherosclerosis by reducing hypercholesterolemia in rabbits fed a high- cholesterol diet. J Nutr Sci Vitaminol (Tokyo). 2010;56(1):34-40.
28. Choi EY, Cho YO. The effects of physical training on antioxidative status under exercise-induced
oxidative stress. Nutr Res Pract. 2007;1(1):14-8.
29. Cingi C, Conk-Dalay M, Cakli H, Bal C. The effects of spirulina on allergic rhinitis. Eur Arch
Otorhinolaryngol. 2008;265(10):1219-23.
30. Dagnelie PC, van Staveren WA, van den Berg H. Vitamin B-12 from algae appears not to be
bioavailable. Am J Clin Nutr. 1991;53(3):695-7.
31. Davies KJ, Goldberg AL. Proteins damaged by oxygen radicals are rapidly degraded in extracts of
red blood cells. J Biol Chem. 1987;262:8227-34.
32. Davies KJ, Quintanilha AT, Brooks GA, Packer L. Free radicals and tissue damage produced by
exercise. Biochem Biophys Res Commun. 1982;107(4):1198-205.
33. Dillon JC, Phuc AP, Dubacq JP. Nutritional value of the alga Spirulina. World Rev Nutr Diet. 1995;77:32-46.
34. Dündar Y, Aslan R. Oksidan-antioksidan denge ve korunmasında vitaminlerin rolü. Hayvancılık
Arastırma Dergisi 1999; 9(1- 2): 32-9.
35. Elhadd TA, Neary R, Abdu TA, Kennedy G, Hill A, McLaren M, Akber M, Belch JJ, Clayton RN.
Influence of the hormonal changes during the normal menstrual cycle in healthy young women on soluble adhesion molecules, plasma homocysteine, free radical markers and lipoprotein fractions. Int Angiol. 2003;22(3):222-8.
36. Fang Y, Yang S, Wu G. Free radicals, antioxidants, and nutrition. Nutrition 2002;18:872-79. 37. Faruque MO, Khan MR, Rahman MM, Ahmed F. Relationship between smoking and antioxidant
59
38. Finaud J, Lac G, Filaire E. Oxidative stres: relationship with exercise and training. Sports Med
2006;36(4):327-58.
39. Fisher-Wellman K, Bloomer RJ. Acute exercise and oxidative stres: a30 year history. Dyn Med
2009;13(8):1.
40. Freitas M, Gomes A, Porto G, Fernandes E. Nickel induces oxidative burst, NF-κB activation and
interleukin-8 production in human neutrophils.J Biol Inorg Chem. 2010;15(8):1275-83.
41. Frie B, Stocker R, Ames BN. Antioxidant defences and lipid peroxidation in human blood plasma.
Proc Natl Acad Sci. 1988;37:569–71.
42. Gemma C, Mesches MH, Sepesi B, Choo K, Holmes DB, Bickford PC. Diets enriched in foods
with high antioxidant activity reverse age-induced decreases in cerebellar beta-adrenergic function and increases in proinflammatory cytokines.J Neurosci. 2002 Jul 15;22(14):6114-20.
43. Giulivi C, Cadenas E. Heme protein radicals: formation, fate, and biological consequences. Free
Radic Biol 1998;24(2):269-79.
44. Gomes EC, Silva AN, de Oliveira MR. Oxidants, antioxidants, and the beneficial roles of
exercise-induced production of reactive species.Oxid Med Cell Longev. 2012;2012:756132.
45. Gomez-Cabrera MC, Borras C, Pallardo FV, Sastre J, Ji LL, Vina J. Decreasing xanthine oxidase-
mediated oxidative stress prevents useful cellular adaptations to exercise in rats. J Physiol 2005;267:113-20.
46. Gómez-Coronado DJ, Ibañez E, Rupérez FJ, Barbas C. Tocopherol measurement in edible
products of vegetable origin.J Chromatogr A. 2004;1054(1-2):227-33.
47. Gupta S, Hrishikeshvan HJ, Sehajpal PK. Spirulina protects against rosiglitazone induced
osteoporosis in insulin resistance rats. Diabetes Res Clin Pract. 2010;87(1):38-43.
48. Gutteridge JM.Biological origin of free radicals, and mechanisms of antioxidant protection.Chem Biol Interact. 1994;91(2-3):133-40.
49. Halliwel B, Gutterıdge JMC. Free radicals in biology and medicine. New York. Oxford Science
Publications. 1999.
50. Halliwell B, Gutteridge JMC. Free Radicals in Biology and Medicine, Third Edition, Oxford
Science Publications, 2001; 22-24.
51. Halliwell B, Gutteridge JMC. Oxygen toxicity, oxygen radicals, transition metals and disease.
Biochem J. 1984;219:1-14.
52. Halliwell B.Free radicals and metal ions in health and disease.Proc Nutr Soc. 1987;46(1):13-26.
53. Halliwell B. Mechanisms involved in the generation of free radicals. Pathol Biol (Paris). 1996;44(1):6-13.
54. Hayashi K, Hayashi T, Kojima I. A natural sulfated polysaccharide, calcium spirulan, isolated from Spirulina platensis: in vitro and ex vivo evaluation of anti-herpes simplex virus and anti- human immunodeficiency virus activities. AIDS Res Hum Retroviruses. 1996;12(15):1463-71.
55. Hayashi O, Katoh T, Okuwaki Y. Enhancement of antibody production in mice by dietary Spirulina platensis. J Nutr Sci Vitaminol (Tokyo). 1994;40(5):431-41.
56. Hellsten Y, Frandsen U, Orthenblad N, Sjødin B, Richter EA. Xanthine oxidase in human skeletal
60
57. Hernández-Corona A, Nieves I, Meckes M, Chamorro G, Barron BL. Antiviral activity of
Spirulina maxima against herpes simplex virus type 2. Antiviral Res. 2002;56(3):279-85.
58. Huang CC, Lin TJ, Lu YF, Chen CC, Huang CY, Lin WT. Protective effects of L-arginine
supplementation against exhaustive exercise-induced oxidative stress in young rat tissues. Chin J Physiol. 2009;52(5):306-15.
59. Hwang C, Sinskey AJ, Lodish HF. Oxidized redox state of glutathione in the endoplasmic reticulum.Science. 1992;257(5076):1496-502.
60. Inal M, Akyüz F, Turgut A, Getsfrid WM. Effect of aerobic and anaerobic metabolism on free radical generation swimmers. Med Sci Sports Exerc. 2001;33(4):564-7.
61. Ismail MF, Ali DA, Fernando A, Abdraboh ME, Gaur RL, Ibrahim WM, Raj MH, Ouhtit A.
Chemoprevention of rat liver toxicity and carcinogenesis by Spirulina. Int J Biol Sci. 2009 Jun 2;5(4):377-87.
62. Ji LL. Antioxidants and oxidative stress in exercise.Proc Soc Exp Biol Med. 1999;222(3):283-92.
63. Ji LL. Exercise at old age: does it increase or alleviate oxidative stress? Ann N Y Acad Sci.
2001;928:236-47.
64. Jorjani, G., Amirani, P. Antibacterial activities of Spirulina. Maj. Iimy Puz. Danisk.Jundi Shap,
1978, 1:14-18.
65. Judge AR, Dodd SL. Xanthine oxidase and activated neutrophils cause oxidative damage to
skeletal muscle after contractile claudication. Am J Physiol Heart Circ Physiol. 2004;286:H252-6.
66. Kalafati M, Jamurtas AZ, Nikolaidis MG, Paschalis V, Theodorou AA, Sakellariou GK,
Koutedakis Y, Kouretas D. Ergogenic and antioxidant effects of spirulina supplementation in humans.Med Sci Sports Exerc. 2010;42(1):142-51.
67. Kapoor R, Mehta U. Supplementary effect of spirulina on hematological status of rats during
pregnancy and lactation. Plant Foods Hum Nutr. 1998;52(4):315-24.
68. Karadeniz A, Cemek M, Simsek N. The effects of Panax ginseng and Spirulina platensis on hepatotoxicity induced by cadmium in rats. Ecotoxicol Environ Saf. 2009;72(1):231-5.
69. Karoui H, Hogg N, Fréjaville C, Tordo P, Kalyanaraman B. Characterization of sulfur-centered radical intermediates formed during the oxidation of thiols and sulfite by peroxynitrite. ESR- spin trapping and oxygen uptake studies.J Biol Chem. 1996;271(11):6000-9.
70. Kato T, Takemoto K. Effects of spirulina on hypercholesterolemia and fatty liver in rats. Japan
Nutr Assoc Jour. 1984;37:321-23.
71. Kayalı R, Çakatay U. Protein oksidasyonunun ana mekanizmaları. CerrahpaĢa J Med. 2004;35:83-
9.
72. Khan M, Shobha JC, Mohan IK, Naidu MU, Sundaram C, Singh S, Kuppusamy P, Kutala VK.
Protective effect of Spirulina against doxorubicin-induced cardiotoxicity. Phytother Res. 2005;19(12):1030-7.
73. Khan M, Shobha JC, Mohan IK, Rao Naidu MU, Prayag A, Kutala VK. Spirulina attenuates
cyclosporine-induced nephrotoxicity in rats.J Appl Toxicol. 2006;26(5):444-51.
74. Khan Z, Bhadouria P, Bisen PS. Nutritional and therapeutic potential of Spirulina. Curr Pharm
61
75. Kılınç K, Kılınç A. Oksijen toksisitesinin aracı molekülleri olarak oksijen radikalleri. Hacettepe
Tıp Dergisi. 2002;33(2):110-18.
76. Kılınç A, Kılınç K. Nitrik oksit, biyolojik fonksiyonları ve toksik etkileri. Ankara, Turkey: Palme
Yayıncılık; 2003.
77. Kojo S. Vitamin C: Basic metabolism and its function as an index of oxidative stress.Curr Med
Chem. 2004;11(8):1041-64.
78. Korivi M, Hou CW, Huang CY, Lee SD, Hsu MF, Yu SH, Chen CY, Liu YY, Kuo CH.
Ginsenoside-Rg1 Protects the Liver against Exhaustive Exercise-Induced Oxidative Stress in Rats. Evid Based Complement Alternat Med. 2012;2012:932165.
79. Krinsky NI. Mechanism of action of biological antioxidants. Proc Soc Exp Biol Med.
1992;200:248–54.
80. Kuhad A, Tirkey N, Pilkhwal S, Chopra K. Effect of Spirulina, a blue green algae, on gentamicin-
induced oxidative stress and renal dysfunction in rats. Fundam Clin Pharmacol. 2006;20(2):121-8.
81. Layam A, Reddy CLK. Antidiabetic property of spirulina. Diabetologia Croatica. 2006;35:29-30. 82. Leeuwenburgh C, Heinecke JW. Oxidative stress and antioxidants in exercise. Curr Medic Chem
2001;8:829-38.
83. Lobo V, Patil A, Phatak A, Chandra N.Free radicals, antioxidants and functional foods: Impact on human health.Pharmacogn Rev. 2010;4(8):118-26.
84. Lowry OH, Risebrough NJ, Farr AL, Randal RJ. Protein measurement with folin phenol reagent. J
Biol Chem. 1951;193:265-75.
85. Lu HK, Hsieh CC, Hsu JJ, Yang YK, Chou HN. Preventive effects of Spirulina platensis on skeletal muscle damage under exercise-induced oxidative stress. Eur J Appl Physiol. 2006;98(2):220-6.
86. Masella R, Di Benedetto R, Varì R, Filesi C, Giovannini C. Novel mechanisms of natural antioxidant compounds in biological systems: involvement of glutathione and glutathione- related enzymes. J Nutr Biochem. 2005;16(10):577-86.
87. Maughan RJ, Depiesse F, Geyer H. The use of dietary supplements by athletes. J Sports Sci.
2007;25:103-13.
88. McArdle WD, Katch FI, Katch VL. Exercise Physiology: Nutrition, Energy, and Human
Performance, Lippincott Williams &Wilkins, Philadelphia, Pa, USA, 2009.
89. McBride JM, Kraemer WJ. Free radicals, exercise, and antioxidants. Nat Strenght Cond Assoc
1999;13:175-83.
90. McCord JM, Fridovich I. The reduction of cytochrome c by milk xanthine oxidase. J Biol Chem
1968;243:5753-60.
91. McCord JM. Oxygen-derived free radicals in postischemic tissue injury. N Engl J Med.
1985;312(3):159-63.
92. Miranda MS, Cintra RG, Barros SB, Mancini Filho J. Antioxidant activity of the microalga Spirulina maxima. Braz J Med Biol Res. 1998;31(8):1075-9.
93. Misra HP, Fridovich I. The generation of superoxide radical during the autoxidation of
62
94. Moura LP, Puga GM, Beck WR, Teixeira IP, Ghezzi AC, Silva GA, Mello MA. Exercise and spirulina control non-alcoholic hepatic steatosis and lipid profile in diabetic Wistar rats.Lipids Health Dis. 2011;10:77.
95. Muthuraman P, Senthilkumar R, Srikumar K. Alterations in beta-islets of Langerhans in alloxan
induced diabetic rats by marine Spirulina platensis. J Enzyme Inhib Med Chem. 2009;24(6):1253-6.
96. Nishino T, Okamoto K, Eger BT, Pai F, Nishino T. Mammalian xanthien oxidoreductase-
mechanism of transition from xanthine dehydrogenase to xanthine oxidase. FEBS J 2008;275 (13):3278-89.
97. Nordberg J, Arnér ES. Reactive oxygen species, antioxidants, and the mammalian thioredoxin system.Free Radic Biol Med. 2001;31(11):1287-312.
98. Ohishi S, Kizaki T, Ookawara T, Toshinai K, Haga S, Karasawa F, Satoh T, Nagata N, Ji LL,
Ohno H. The effect of exhaustive exercise on the antioxidant enzyme system in skeletal muscle from calcium-deficient rats. Pflugers Arch 1998;435:767-74.
99. Padayatty SJ, Katz A, Wang Y, Eck P, Kwon O, Lee JH, Chen S, Corpe C, Dutta A, Dutta SK,
Levine M. Vitamin C as an antioxidant: Evaluation of its role in disease prevention. J Am Coll Nutr. 2003;22:18–35.
100. Parikh P, Mani U, Iyer U.Role of Spirulina in the Control of Glycemia and Lipidemia in Type 2
Diabetes Mellitus.J Med Food. 2001;4(4):193-199.
101. Park JR, Tappel AL. Protein damage and lipid peroxidation: Effects of diethyl maleate,
bromotrichloromethane and vitamin E on ammonia, urea and enzymes involved in ammonia metabolism. Toxicol Lett. 1991;58:29-36.
102. Peternelj TT, Coombes JS. Antioxidant supplementation during exercise training: beneficial or
detrimental?Sports Med. 2011;41(12):1043-69.
103. Ponce-Canchihuamán JC, Pérez-Méndez O, Hernández-Muñoz R, Torres-Durán PV, Juárez-
Oropeza MA. Protective effects of Spirulina maxima on hyperlipidemia and oxidative-stress induced by lead acetate in the liver and kidney. Lipids Health Dis. 2010;9:35.
104. Powers SK, DeRuisseau KC, Quindry J, Hamilton KL. Dietary antioxidants and exercise. J Sports Sci. 2004;22(1):81-94.
105. Pryor WA. Vitamin E and heart disease: basic science to clinical intervention trials.Free Radic Biol Med. 2000;28(1):141-64.
106. Qureshi MA, Ali RA.Spirulina platensis exposure enhances macrophage phagocytic function in
cats. Immunopharmacol Immunotoxicol. 1996;18(3):457-63.
107. Qureshi MA, Garlich JD, Kidd MT. Dietary Spirulina platensis enhances humoral and cell- mediated immune functions in chickens. Immunopharmacol Immunotoxicol. 1996;18(3):465- 76.
108. Radák Z, Asano K, Inoue M, Kizaki T, Oh-Ishi S, Suzuki K, Taniguchi N, Ohno H. Superoxide
dismutase derivative reduces oxidative damage in skeletal muscle of rats during exhaustive exercise. J Appl Physiol. 1995;79:129-35.
109. Radi R, Beckman JS, Bush KM, Freeman BA. Peroxynitrite oxidation of sulfhydryls. The cytotoxic potential of superoxide and nitric oxide.J Biol Chem. 1991;266(7):4244-50.
110. Rauma AL, Mykkänen H. Antioxidant status in vegetarians versus omnivores. Nutrition.
63
111. Reiter RJ. Oxidative processes and antioxidative defense mechanisms in the aging brain. FASEB
J. 1995;9:526-33.
112. Rice-Evans CA, Diplock AT. Current status of antioxidant therapy. Free Radic Biol Med.