SUAT ÇOLAK, Fatime GEYİKOĞLU, HASAN TÜRKEZ, Murat BAKIR, Mirkhalil HUSSEINIGOUZDAGANII, Serpil CAN, Gülşen ÇIĞŞAR, Ali ASLAN

The effects of lichens extracts in the healthy rats and the medical utility of these extracts in the prevention of diabetes-associated multiple organ failures

Bu çalışmada, ilk olarak Cetraria islandica ve Pseudevernia furfuracae türü liken ekstraktlarının sıçanlara ait çeşitli dokular üzerine zararlı etkilerinin olup olmadığı değerlendirilmiştir. Diabetes mellitusa (DM) bağlı oksidatif stres, organlar için büyük bir risk faktörü oluşturmaktadır. Çalışmamızın ikinci bölümünde ise her iki liken ekstaktı uygulamasının tip 1 diyabet kaynaklı organ bozukluklarına karşı koruyucu olup olmadıklarını araştırılmıştır. İki hafta boyunca hem kontrol hem de diyabetli ratlara sulu liken ekstreleri uygulanmıştır. Süre sonunda metabolik değişimler belirlenmiştir. Ondördüncü günde, hayvanların yaşamları servikal dislokasyonla sonlandırıldıktan sonra biyokimya ve genetik çalışmalar için gerekli örnekler alınmıştır. DNAnın oksidatif hasarı 8-hidroksi-2-deoksiguanosin oluşumunda meydana gelen artış ölçülerek hesaplanmıştır. Biyokimyasal parametreler dokularda meydana gelen fonksiyon değişimlerinin gözlenmesi ve değerlendirilmesi için kullanılmıştır. Deney sonuçları tek başına uygulanan liken ekstraktlarının artan dozlarda herhangi bir zararlı etkiye sahip olmadığını göstermiştir. Ayrıca, C. islandica diyabete bağlı artan kan glikoz ve malondialdehit (MDA) seviyesini kısmen düşürmüştür. Antioksidan tedavinin hasta ratlarda organ yetmezliğine karşı fayda sağlayacağı düşünülmektedir. Bununla birlikte, C. islandica nın antioksidan etkisinin diyabet teşvikli bozukluklarda ve DNA hasarına karşı yetersiz olduğu anlaşılmıştır. Sonuç olarak, likenlerin çalışılan doz aralığında güvenli olduğu ve tip 1 diyabetin neden olduğu yaşamsal organlar üzerindeki güçlü oksidatif stres nedeniyle C. islandica sınırlı bir etkiye sahip olduğu gözlenmiştir.

Liken ekstrelerinin sağlıklı ratlar üzerindeki etkileri ve bu ekstrelerin diyabete bağlı çoklu organ yetmezliğinin önlenmesinde medikal kullanımı

In the present study, we firstly assessed Cetraria islandica and Pseudevernia furfuracae to avoid detrimental efects on multiple tissues of rats. Diabetes mellitus (DM) with the subsequent generation of oxidative stress represents a major risk factor for organs. The second aim of this study is to investigate whether administration of both lichens could prevent type 1 diabetes (T1D)-induced organ dysfunctions. During two weeks, both control and diabetic rats were treated with aqueous lichen extracts. The metabolic changes were determined. On day 14, after animals were decapitated, required samples for biochemical and genetic analysis were collected. Oxidative damage of DNA was estimated by measuring the increase in 8-hydroxy-2-deoxyguanosine formation. Biochemical parameters were used to observe and evaluate the functional changes in tissues. Experimental data showed that the increasing doses of lichens alone have not any detrimental efect on above parameters. Moreover, C. islandica decreased the diabetes-induced glucose and malondialdehyde (MDA) levels. Thus, it seemed that the antioxidant treatment has an important efect on the organ failure in ill rats. However, the protective efect of C. islandica was inadequate on diabetes- induced disorders and DNA damages. Lichens are a safe in the studied dose range but the power of C. islandica is limited because of intensive oxidative stress in essential organs of T1D rats.

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1. Grieco F, Sebastiani G, Spagnuolo I, Patti A, Dotta F: Immunology in the clinic review series; focus on type 1 diabetes and viruses: How viral infections modulate beta cell function. Clin Exp Immunol, 168 (1): 24-29, 2012.
2. Baynes JW: Role of oxidative stress in development of complications in diabetes. Diabetes, 40 (4): 405-410, 1991.
3. Hamden K, Carreau S, Boujbiha MA, Lajmi S, Aloulou D, Kchaou D, Elfeki A: Hyperglycaemia, stress oxidant, liver dysfunction and histological changes in diabetic male rat pancreas and liver: Protective efect of 17β-estradiol. Steroids, 73 (5): 495-501, 2008.
4. Behera BC, Mahadik N, Morey M: Antioxidative and cardiovascular- protective activities of metabolite usnic acid and psoromic acid produced by lichen species Usnea complanata under submerged fermentation. Pharm Biol, 50 (8): 968-979, 2012.
5. Odabasoglu F, Aslan A, Cakir A, Suleyman H, Karagoz Y, Halici M, Bayir Y: Comparison of antioxidant activity and phenolic content of three lichen species. Phytother Res,18 (11): 938-941, 2004.
6. Kosanić M, Ranković B: Lichen as possible sources of antioxidants. Pak J Pharm Sci, 24 (2): 165-170, 2011.
7. Vartia KO: Antibiotics in Lichens. The Lichens. 547-561, Academic Press, Inc, New York, 1973.
8. Dülger B, Gücin F, Aslan A: Cetraria islandica (L.) Ach. Likeninin Antimikrobiyal Aktivitesi. Turk J Biol, 22, 111-118, 1998.
9. Bezivin C, Tomasi S, Lohezic-Le Devehat F, Boustie J: Cytotoxic activity of some lichen extracts on murine and human cancer cell lines. Phytomedicine, 10 (6-7): 499-503, 2003.
10. Ren MR, Hur JS, Kim JY, Park KW, Park SC, Seong CN, Jeong IY, Byun MW, Lee MK, Seo KI: Anti-proliferative effects of Lethariella zahlbruckneri extracts in human HT-29 human colon cancer cells. Food Chem Toxicol, 47 (9): 2157-2162, 2009.
11. Mitrović T, Stamenković S, Cvetković V, Toić S, Stanković MRI, Stefanović O, Comić L, Dačić D, Curčić M, Marković S: Antioxidant, antimicrobial and antiproliferative activities of five lichen species. Int J Mol Sci, 12 (8): 5428-5448, 2011.
12. Aslan A, Yazici K, Karagöz Y: Lichen fora of the Murgul district, Artvin, Turkey. J Exp Bot, 50, 77-81, 2002.
13. Archer D, Connerton I, MacKenzie D: Filamentous fungi for production of food additives and processing aids. Adv Biochem Eng Biotechnol, 111, 99-147, 2008.
14. Elsherbiny NM, El Galil KHA, Gabr MM, Al-Gayyar MM, Eissa LA, El- Shishtawy MM: Reno-protective efect of NECA in diabetic nephropathy: Implication of IL-18 and ICAM-1. Eur Cytokine Netw, 23 (3): 78-86, 2001.
15. Yamamoto Y, Yamamoto H: Interaction of receptor for advanced glycation end products with advanced oxidation protein products induces podocyte injury. Kidney Int, 82 (7): 733-735, 2012.
16. Abolfathi AA, Mohajeri D, Rezaie A, Nazeri M: Protective efects of green tea extract against hepatic tissue ınjury in streptozotocin-ınduced diabetic rats. Evid Based Complement Alternat Med, 740671, 1-10, 2012.
17. Ahola AJ, Mikkilä V, Saraheimo M, Wadén J, Mäkimattila S, Forsblom C, Freese R, Groop PH, FinnDiane Study Group: Sense of coherence, food selection and leisure time physical activity in type 1 diabetes. Scand J Public Health, 40 (7): 621-628, 2012.
18. Yu SM, EI S, Ee L: Cetraria islandica (l.) ach.: Chemical composition and perspectives of using in medicine. Rastitelnye Resursy, 35 (7): 106- 115, 1999.
19. Türkez H, Geyikoglu F, Aslan A, Karagöz Y, Türkez O, Anar M: Antimutagenic efects of lichen Pseudovernia furfuracea (L.) Zoph. extracts against the mutagenicity of afatoxin B1 in vitro. Toxicol Ind Health, 26 (9): 625-631, 2010.
20. Roy MD: Approach for assessing total cellular DNA damage. Biotechniques, 42 (4): 425-429, 2007.
21. Aslan A: Lichens from the regions of Artvin, Erzurum, and Kars (Turkey). J Exp Bot, 48 (3): 143-147, 2000.
22. Vijayakumar M, Govindarajan R, Rao G, Rao CV, Shirwaikar A, Mehrotra S, Pushpangadan P: Action of Hygrophila auriculata against streptozotocin-induced oxidative stress. J Ethnopharmacol, 104 (7): 356- 361, 2006.
23. Çelik VK, Sahin ZD, Sari I, Bakir S: Comparison of oxidant/ antioxidant, detoxification systems in various tissue homogenates and mitochondria of rats with diabetes ınduced by streptozocin. Exp Diabetes Res, 2012 (1): 1-8, 2012.
24. Okaha H: Assay for lipid peroxide in animal tissue by thiobarbituric acid reaction. Anal Biochem, 95 (2): 351-358, 1979.
25. Kuchino Y, Mori F, Kasai H, Inoue H, Iwai S, Miura K, Ohtsuka E, Nishimura S: Misreading of DNA templates containing 8-hydroxy- deoxyguanosine at the modifed base and at adjacent residues. Nature, 327, 77-79, 1987.
26. Kasai H, Nishimura S, Kurokawa Y, Hayashi Y: Oral administration of renal carcinogen, potassium bromate, specifcaly produces 8.-hydroxy- deoxyguanosine in rat target organ DNA. Carcinogenesis, 8, 1959-1961, 1987.
27. Dai Nakae, Yozo Kobayashi, Hiroyuki Akai: Involvement of 8-Hydroxyguanine formation in the initiation of rat liver carcinogenesis by low dose levels of NNitrosodiethylamine. Cancer Res, 57, 1281-1287, 1997.
28. Ritchie RH, Delbridge L: Cardiac hypertrophy, substrate utilization and metabolic remodelling: cause or efect? Clin Exp Pharmacol Physiol, 33 (1-2): 159-166, 2006.
29. Esterbauer H, Schaur RJ, Zollner H: Chemistry and biochemistry of 4-hydroxynonenal, malonaldehyde and related aldehydes. Free Radic Biol Med, 11 (1): 81-85, 1991.
30. Xiong X, Wang W, Wang LR, Jin LD, Lin LN: Diabetes increases infammation and lung injury associated with protective ventilation strategy in mice. Int Immunopharmacol, 13 (3): 280-283, 2012.
31. Rentoukas E, Tsarouhas K, Kaplanis I, Korou E, Nikolaou M, Marathonitis G, Kokkinou S, Haliassos A, Mamalaki A, Kouretas D, Tsitsimpikou C: Connection between telomerase activity in PBMC and markers of infammation and endothelial dysfunction in patients with metabolic syndrome. PloS one , 7 (4): e35739, 2012.
32. Perez-Gutierrez RM, Damian-Guzman MM: A Potent α-Glucosidase and α-amylase ınhibitor ısolated from azadirachta indica leaves and in vivo antidiabetic property in streptozotocin-nicotinamide-ınduced Type 2 diabetes in mice. Biol Pharm Bull, 35 (9): 1516-1520, 2012.
33. Sankar P, Subhashree S, Sudharani S: Efect of Trigonella foenum- graecum seed powder on the antioxidant levels of high fat diet and low dose streptozotocin induced type II diabetic rats. Eur Rev Med Pharmacol Sci, 16 (3): 10-17, 2012.
34. Luo H, Liu YP, Kahng HY, Jung JS, Kahng HY, Koh YJ, Hur JS: The in vitro antioxidant properties of chinese highland lichens. J Microbiol Biotechnol, 20 (11): 1524-1528, 2010.
35. Murri M, Garcia-Delgado R, Alcázar-Ramirez J: Assessment of cellular and plasma oxidative stress in SAHS patients before and after continuous positive airway pressure treatment. Clin Lab, 56 (9-10): 397- 405, 2010.
36. Bingöl SA, Kocamiş H: Sağlıklı ve diabet oluşturulmuş farelerin böbrek dokusunda katalaz enziminin RT-PCR ile gen ve immunohistokimyasal olarak protein ekspresyonu. Kafkas Univ Vet Fak Derg, 16 (5): 825-834, 2010.
37. Slezak B, Hatch G, DeVito M, Diliberto JJ, Slade R, Crissman K, Hassoun E, Birnbaum LS: Oxidative stress in female B6C3F1 mice following acute and subchronic exposure to 2, 3, 7, 8-tetrachlorodibenzo- p-dioxin (TCDD). Toxicol Sci, 54 (2): 390-398, 2010.
38. Ralph DM, Robinson SR, Campbell MS, Bishop GM: Histidine, cystine, glutamine, and threonine collectively protect astrocytes from the toxicity of zinc. Free Radic Biol Med, 49 (4): 649-657, 2010.
39. Freysdottir J, Omarsdottir S, Ingólfsdóttir K, Vikingsson A, Olafsdottir ES: In vitro and in vivo immunomodulating effects of traditionally prepared extract and purified compounds from Cetraria islandica. Int Immunopharmacol, 8 (3): 423-430, 2008.
40. Cernescu I, Tarţău L, Macavei A, Lupuşoru CE: Efects of a Cetraria islandica extract in monotherapy and in association with magnesium in an experimental-induced hepatopathy model. Rev Med Chir Soc Med Nat Iasi, 115 (4): 1195-1199, 2011.
41. Quick VM, McWilliams R, Byrd-Bredbenner C: Case-control study of disturbed eating behaviors and related psychographic characteristics in young adults with and without diet-related chronic health conditions. Eat Behav, 13 (3): 207-213, 2012.
42. Gierach M, Gierach J, Skowrońska A, Rutkowska E, Spychalska M, Pujanek M, Junik R: Hashimotos thyroiditis and carbohydrate metabolism disorders in patients hospitalised in the Department of Endocrinology and Diabetology of Ludwik Rydygier Collegium Medicum in Bydgoszcz between 2001 and 2010. Endokrynol Pol, 63 (1): 14-17, 2012.
43. Mansur LP, Lopes SD, dos Santos LE, Paes de Miranda M, Lopes Rosado E: Infuence of fat intake on body composition, lipemia and glycemia of type 1 diabetics. Nutr Hosp, 26 (5): 1110-1114, 2011.
44. Zou CL, Wang JY, Wang SY, Huang F, Ren Z, Chen Z, Zhang Y: Characterizing the induction of diabetes in juvenile cynomolgus monkeys with diferent doses of streptozotocin. Sci China Life Sci, 55 (3): 210-218, 2012.
45. Tunali Akbay T, Yarat A, Sacan O, Yanardag R: The effect of glurenorm (Gliquidone) on aorta in STZ ınduced diabetic rats. Kafkas Univ Vet Fak Derg, 17 (2): 235-238, 2011.
46. Malekinejad H, Rezabakhsh A, Rahmani F, Hobbenaghi R: Silymarin regulates the cytochrome P450 3A2 and glutathione peroxides in the liver of streptozotocin-induced diabetic rats. Phytomedicine, 19 (7): 583-590, 2012.
47. Stevens LA, Levey AS: Measurement of kidney function. Med Clin North Am, 89 (3): 457-465, 2005.
48. OBrien RM, Granner DK: Regulation of gene expression by insulin. Physiol Rev, 76 (4): 1109-1161, 1996.
49. Qi M, Guan X, Zhu L, Wang LJ, Liu L, Yang YP: The efect of resistin on nuclear factor-kB and tumor necrosis factor-a expression in hepatic steatosis. Chin J Hepatol, 20 (1): 40-44, 2012.
50. Palsamy P, Sivakumar S, Subramanian S: Resveratrol attenuates hyperglycemia-mediated oxidative stress, proinfammatory cytokines and protects hepatocytes ultrastructure in streptozotocinnicotinamide- induced experimental diabetic rats. Chem Biol Interact, 186 (2): 200-210, 2010.
51. Ghaffari H, Ghassam BJ, Prakash H: Hepatoprotective and cytoprotective properties of Hyptis suaveolens against oxidative stress induced damage by CCl 4 and H2O 2. Asian Pac J Trop Biomed, 5 (11): 868- 874, 2012.
52. Xue J, Nguyen DT, Habtezion A: Aryl hydrocarbon receptor regulates pancreatic IL-22 production and protects mice from acute pancreatitis. Gastroenterology, 143 (6): 1670-1680, 2012.
53. El-Demerdash F, Yousef M, El-Naga N: Biochemical study on the hypoglycemic efects of onion and garlic in alloxan-induced diabetic rats. Food Chem Toxicol, 43 (1): 57-63, 2005.
54. Sebesta I: Genetic disorders resulting in hyper-or hypouricemia. Adv Chronic Kidney Dis, 19 (6): 398-403, 2012.
55. Dandona P, Thusu K, Cook S, Snyder B, Makowski J, Armstrong D, Nicotera T: Oxidative damage to DNA in diabetes mellitus. The Lancet, 347 (8999): 444-445, 1996.
56. Park KS, Kim JH, Kim MS, Kim JM, Kim SK, Choi JY, Chung MH, Han B, Kim SY, Lee HK: Efects of insulin and antioxidant on plasma 8-hydroxyguanine and tissue 8-hydroxydeoxyguanosine in streptozotocin-induced diabetic rats. Diabetes, 50 (12): 2837-2841, 2001.
57. Tsuruya K, Furuichi M, Tominaga Y, Shinozaki M, Tokumoto M, Yoshimitsu T, Fukuda K, Kanai H, Hirakata H, Iida M, Nakabeppu Y: Accumulation of 8-oxoguanine in the cellular DNA and the alteration of the OGG1 expression during ischemia-reperfusion injury in the rat kidney. DNA Repair, 2 (2): 211-229, 2003.
58. Leinonen J, Lehtimäki T, Toyokuni S, Okada K, Tanaka T, Hiai H, Ochi H, Laippala P, Rantalaiho V, Wirta O, Pasternack A, Alho H: New biomarker evidence of oxidative DNA damage in patients with non- insulin-dependent diabetes mellitus. FEBS Letters, 417 (1): 150-152, 1997.
59. Hendarto H, Inoguchi T, Maeda Y, Ikeda N, Zheng J, Takei R, Yokomizo H, Hirata E, Sonoda N, Takayanagi R: GLP-1 analog liraglutide protects against oxidative stress and albuminuria in streptozotocin- induced diabetic rats via protein kinase A-mediated inhibition of renal NAD (P) H oxidases. Metabolism, 61 (10): 1422-1434, 2012.
60. Buchko G, Cadet J, Labataille P, Ravanat JL: Isolation and Characterization of a new product produced by ıonizing ırradiation and Type I photosensitization of 2-deoxyguanosine in oxygen- saturated aqueous solution: (2S)-2, 5-anhydro-1-(2-deoxy-β-d-erythro- pentofuranosyl)-5-guanidinylidene-2-hydroxy-4-oxoimidazolidine. Int J Radiat Biol, 63 (3): 669-676, 1993.
61. Lee EY, Chung CH, Kim JH, Joung HJ, Hong SY: Antioxidants ameliorate the expression of vascular endothelial growth factor mediated by protein kinase C in diabetic podocytes. Nephrol Dial Transplant, 21(6): 1496-1503, 2006.