STZ İle Diyabet Oluşturulan Sıçanlarda Rosa Pisiformis(Christ) D.Sons'un Bazı Metabolik Enzim Aktiviteleri Üzerine Etkisi

Öz

Bu çalışmada Streptozotosin (STZ) ile diyabet oluşturulan sıçanlarda Rosa pisiformis (Christ) D.Sosn. (VANF F13827 END.) 'in bazı metabolik enzimler üzerine in vivo etkilerinin araştırılması amaçlandı. 32 adet wistar albino cinsi erkek sıçan dört gruba ayrıldı. Grup I:Kontrol, Grup II:Streptozotosin, Grup III: Rosa pisiformis, Grup IV: Streptozotosin + Rosa pisiformis. Deneysel çalışma 30 gün sürdürüldü ve enzim aktiviteleri spektrofotometrik olarak ölçüldü. Glukoz 6-fosfat dehidrogenaz (G6PD) aktivitesinde R.p.meyve ekstraktı ve STZ+R.p meyve ekstraktı uygulanan gruplarda kontrolle kıyaslandığında anlamlı düzeyde artış görüldü(p˂0.001). 6-fosfoglukonat dehidrogenaz (6PGD) enzim aktivitesi diyabet oluşturulan grupta kontrole oranla azaldı. Aksine R.p meyve ekstraktı ve STZ+R.p meyve ekstraktı uygulanan grupta arttı. Glutatyon reduktaz (GR) enzim aktivitesi R.p meyve ekstraktı uygulanan grupta kontrole oranla istatistiksel olarak anlamlı düzeyde yükseldi (p˂0.001). Tioredoksin redüktaz (TrxR) aktivitesi diyabetik sıçanlarda kontrol ile karşılaştırıldığında istatistiksel olarak önemli bir azalma göstermezken, Rosa pisiformis meyve ekstraktı uygulanan grupta arttı. Glutatyon S-transferaz (GST) enzim aktivitesinin STZ uygulanan grupta kontrole oranla anlamlı şekilde azaldığı görüldü (p˂0.05). Sonuç olarak; Rosaceae familyasına ait endemik bir tür olarak yetişen Rosa pisiformis meyvelerinin sıçanlarda 6PGD, TrxR ve GST enzim aktiviteleri üzerine STZ'nin neden olduğu inhibisyonu azaltıcı yada önleyici etkisinin olabileceği düşünülmektedir.

Anahtar Kelimeler

• G6PD
• GR
• GST
• 6PGD
• Rosa pisiformis
• TrxR

The Effect of Rosa Pisiformis (Christ) D.Sosn on Some Metabolic Enzyme Activities in STZ Applied Diabetic Rats

Öz

This study was aimed to study in vivo impacts of Rosa pisiformis (Christ) D.Sosn. (VANF F13827 END.) on some metabolic enzymes (G6PD, 6PGD, GR, TrxR and GST) in Streptozotocin (STZ) applied diabetic rats. 32 male Wistar albino rats divided four groups. Group I: Control, Group II:Streptozotocin, Group III: Rosa pisiformis and Group IV: Streptozotocin+Rosa pisiformis. Experimental study contunied for 30 days and enzyme activities were spectrophotometrically measured. R.p.fruit extract and STZ+R.p. fruit extract administrations increased Glucose 6-phosphate dehydrogenase (G6PD) activity meaningfully compared to control (p˂0.001). 6-phosphogluconate dehydrogenase (6PGD) enzyme activity reduced in diabetes group compared to control, whereas it increased in R.p. fruit extract and STZ+R.p. fruit administered groups. Glutathione reductase (GR) activity raised in R.p. fruit administered group compared to control group meaningfully (p˂0.001). Thioredoxin reductase (TrxR) activity decrease no statistical importance in diabetic rats compared control whereas this activity increased in Rosa pisiformis fruit extract group. Glutathione S-transferases (GST) enzyme activity reduction significantly in STZ group compared to control (p˂0.05). As a result, It is thought that the fruits of Rosa pisiformis, which grows as an endemic species belonging to the Rosaceae family, may have a reducing or preventing effect on the 6PGD, TrxR and GST enzyme activities in rats by inhibiting caused by STZ.

Anahtar Kelimeler

• G6PD
• GR
• GST
• 6PGD
• Rosa pisiformis
• TrxR

Kaynakça

1. Acosta-Montoya Ó, Vaillant F, Cozzano S, Mertz C, Pérez AM, Castro MV, 2010. Phenolic content and antioxidant capacity of tropical highland blackberry (Rubus adenotrichus Schltdl.) during three edible maturity stages. Food Chemistry, 119(4), 1497–1501.
2. Adem S, Ciftci M, 2016. Purification and biochemical characterization of glucose 6-phosphate dehydrogenase, 6-phosphogluconate dehydrogenase and glutathione reductase from rat lung and inhibition effects of some antibiotics. Journal of Enzyme Inhibition and Medicinal Chemistry, 6366(January), 1–7.
3. Akbarzadeh A, Norouzian D, Mehrabi MR, Jamshidi S, Farhangi A, Allah Verdi A,Rad BL, 2007. Induction of diabetes by Streptozotocin in rats. Indian Journal of Clinical Biochemistry, 22(2), 60–64.
4. Akkemik E, Şentürk M, Özgeriş FB, Taşer P, Ciftci M, 2011. In vitro effects of some drugs on human erythrocyte glutathione reductase. Turkish Journal of Medical Sciences, 41(2), 235-241.
5. Au SWN, Gover S, Lam VMS, Adams MJ, 2000. Human glucose-6-phosphate dehydrogenase: The crystal structure reveals a structural NADP+ molecule and provides insights into enzyme deficiency. Structure, 8(3), 293–303.
6. Aybek H, Temel Y, Ahmed BM, Ağca C. A, Çiftci M, 2020. Deciphering of The Effect of Chemotherapeutic Agents on Human Glutathione S-Transferase Enzyme and MCF-7 Cell Line. Protein & Peptide Letters, 27, 1–7.
7. Balasundram N, Sundram K, Samman S, 2006. Phenolic compounds in plants and agri-industrial by-products: Antioxidant activity, occurrence, and potential uses. Food Chemistry, 99(1), 191–203.
8. Bayindir S, Temel Y, Ayna A, Ciftci M, 2018. The synthesis of N-benzoylindoles as inhibitors of rat erythrocyte glucose-6-phosphate dehydrogenase and 6-phosphogluconate dehydrogenase. Journal of Biochemical and Molecular Toxicology, 32(9), 1–9

9. Bayramoğlu Akkoyun M, Bengü AŞ, Temel Y, Akkoyun HT, Ekin S, Ciftci M, 2018. The effect of astaxanthin and cadmium on rat erythrocyte G6PD, 6PGD, GR, and TrxR enzymes activities in vivo and on rat erythrocyte 6PGD enzyme activity in vitro. Journal of Biochemical and Molecular Toxicology, 32(8), 1–5.
10. Bayramoğlu M, Ekin S, Kızıltaş H, Oto G, Susen EA, Özgökçe F, 2016. Antioxidant properties of Rosa pisiformis and its protective effect against isoproterenol-induced oxidative stress in rats.Journal of Biochemistry/Turk Biyokimya Dergisi, 41 (4): 232-242.
11. Beutler E, 1971. Red cell metabolism. A manual of biochemical methods. Vol. 12.
12. Beydemir S, Ciftci M, Yilmaz H, Kufrevioglu O, 2004. 6-Phosphogluconate Dehydrogenase: Purification, Characterization and Kinetic Properties from Rat Erythrocytes. Turkish J. Vet. Animal Sci., 28, 707–714.
13. Branco V, Godinho-santos A, Gonçalves J, Lu J, Holmgren A, Carvalho C, 2014. Free Radical Biology and Medicine Mitochondrial thioredoxin reductase inhibition , selenium status , and Nrf-2 activation are determinant factors modulating the toxicity of mercury compounds. Free Radical Biology and Medicine, 73, 95–105.
14. Carlberg I, Mannervik B, 1986. Reduction of 2, 4, 6-trinitrobenzenesulfonate by glutathione reductase and the effect of NADP+ on the electron transfer. Journal of Biological Chemistry, 261(4), 1629-1635.
15. Ciftci M, Bilici D, Kufrevioglu OI, 2001. Effects of metamizol and magnesium sulfate on enzyme activities of glucose-6-phosphate dehydrogenase from human erythrocytes in vitro and from rat erythrocytes in vivo. Pharmacol Res, 44(1), 7–11
16. Cilaker-Mıcılı S, Ergür Bu, Özoğul C, Sarıoğlu S, Bağrıyanık A, Tuğyan K, Pekçetin Ç, Sönmez Ü, Tekmen I, Erbil G, Akdoğan Gg, Özyurt D, Buldan Z, 2012. Deneysel Hipertansiyon ve Diyabet Modeli Oluşturulan Sıçanlarda Böbreğin İmmunohistokimyasal Olarak İncelenmesi, 91–101.
17. Deshpande AD, Harris-Hayes M, Schootman M, 2008. Epidemiology of diabetes and diabetes-related complications. Physical therapy, 88: 1254-1264.
18. Djeridane A, Yousfi M, Nadjemi B, Boutassouna D, Stocker P, Vidal N, 2006. Antioxidant activity of some algerian medicinal plants extracts containing phenolic compounds. Food Chemistry, 97(4), 654–660.
19. Ercisli S, 2005. Rose (Rosa spp.) germplasm resources of Turkey. Genetic Resources and Crop Evolution, 52(6), 787–795.
20. Ercisli S, 2007. Chemical composition of fruits in some rose (Rosa spp.) species. Food Chemistry, 104(4), 1379–1384.
21. Federiuk IF, Casey HM, Quinn MJ, Wood MD, Ward WK, 2004. Induction of type-1 diabetes mellitus in laboratory rats by use of alloxan: Route of administration, pitfalls, and insulin treatment. Comparative Medicine, 54(3), 252–257.
22. Gholamhoseinian A, Fallah H, Sharifi far F, 2009. Inhibitory effect of methanol extract of Rosa damascena Mill. flowers on α-glucosidase activity and postprandial hyperglycemia in normal and diabetic rats. Phytomedicine, 16(10), 935–941.
23. Habig WH, Pabst MJ, Jakoby WB, 1974. Glutathione S-transferases the first enzymatic step in mercapturic acid formation. Journal of Biological Chemistry, 249, 7130–7139.
24. Halvorsen BL, Holte K, Myhrstad MCW, Barikmo I, Hvattum E, Remberg SF, Blomhoff R, 2002. A systematic screening of total antioxidants in dietary plants. Journal of Nutrition, 132(3), 461–471.
25. Holmgren A, 1977. Bovine thioredoxin system. Purification of thioredoxin reductase from calf liver and thymus and studies of its function in disulfide reduction. Journal of Biological Chemistry, 252(13), 4600-4606.
26. Imaeda A, Kaneko T, Aoki T, Kondo Y, Nagase H, 2002. DNA damage and the effect of antioxidants in streptozotocin-treated mice. Food and Chemical Toxicology, 40(7), 979–987.
27. Junod A, Lambert AE, Stauffacher W, Renold AE, 1969. Diabetogenic action of streptozotocin: relationship of dose to metabolic response. The Journal of clinical investigation, 48(11), 2129–2139.
28. Karaman M, Temel Y, Bayindir S, 2020. Inhibition effect of rhodanines containing benzene moieties on pentose phosphate pathway enzymes and molecular docking. Journal of Molecular Structure, 1220, 128700.
29. Kifle Z D, Belayneh YM, 2020. Antidiabetic and Anti-hyperlipidemic Effects of the Crude Hydromethanol Extract of Hagenia abyssinica (Rosaceae) Leaves in Streptozotocin-Induced Diabetic Mice. Diabetes, Metabolic Syndrome and Obesity: Targets and Therapy, 13, 4085.
30. Kozar RA, Weibel CJ, Cipolla J, Klein AJP, Haber MM, Abedin MZ, Trooskin SZ, 2000. İnjury, 28(7).
31. Lee SE, Hwang HJ, Ha JS, Jeong HS, Kim JH, 2003. Screening of medicinal plant extracts for antioxidant activity. Life Sciences, 73(2), 167–179.
32. Lenzen S, 2008. The mechanisms of alloxan- and streptozotocin-induced diabetes. Diabetologia, 51(2), 216–226.
33. López V, Akerreta S, Casanova E, García-Mina JM, Cavero RY, Calvo MI, 2007. In vitro antioxidant and anti-rhizopus activities of lamiaceae herbal extracts. Plant Foods for Human Nutrition, 62(4), 151–155.
34. Maritim AC, Sanders RA, Watkins JB, 2003. Diabetes, oxidative stress, and antioxidants: A review. Journal of Biochemical and Molecular Toxicology, 17(1), 24–38
35. Metelko Z, Pavlić-Renar I, Tomić M, Bratanić N, 2000. New diagnostic criteria and classification of diabetes mellitus. Lijecnicki vjesnik, 122(5–6), 99–102.
36. Nelson DL, Cox MM, 2000. Lehninger principles of biochemistry, Worth Publishers. New York, 407,800-814.
37. Orhan N, Aslan M, Hoşbaş S, Deliorman Orhan D, 2009. Antidiabetic effect and antioxidant potential of Rosa canina fruits. Pharmacognosy Magazine, 5(20), 309–315.
38. Özaslan MS, Balcı N, Demir Y, Gürbüz M, Küfrevioğlu Öİ, 2019. Inhibition effects of some antidepressant drugs on pentose phosphate pathway enzymes. Environmental Toxicology and Pharmacology, 72(March).
39. Öztaşan N, Altinkaynak K, Akçay F, Göçer F, Dane Ş, 2005. Effects of mad honey on blood glucose and lipid levels in rats with streptozocin-induced diabetes. Turkish Journal of Veterinary and Animal Sciences, 29(5), 1093–1096.
40. Pljesa-Ercegovac M, Savic-Radojevic A, Matic M, Coric V, Djukic T, Radic T, Simic T, 2018. Glutathione transferases: Potential targets to overcome chemoresistance in solid tumors. International Journal of Molecular Sciences, 19(12).
41. Rahimi M, Sajadimajd S, Mahdian Z, Hemmati M, Malekkhatabi P, Bahrami G, Derakhshankhah H, 2020. Characterization and anti-diabetic effects of the oligosaccharide fraction isolated from Rosa canina in STZ-Induced diabetic rats. Carbohydrate research, 489, 107927.
42. Rossini AA, Like AA, Chick WL, Appel MC, Cahill GF, 1977. Studies of streptozotocin induced insulitis and diabetes. Proceedings of the National Academy of Sciences of the United States of America, 74(6), 2485–2489.
43. Sen CK, Packer L,1996. Antioxidant and redox regulation of gene transcription. The FASEB Journal, 10(7), 709–720.
44. Sensoy N, Gençoglan G, 2009. Tip I Diyabetli Hastalarda Deri Bulgularının Vücut Kitle İndeksi ve Hba1c İle İlişkisi. Anatolian Journal of Clinical Investigation, 3, 213-217.
45. Sultana B, Anwar F, Ashraf M, 2009. Effect of extraction solvent/technique on the antioxidant activity of selected medicinal plant extracts. Molecules, 14(6), 2167–2180.
46. Szkudelski T, 2001. The mechanism of alloxan and streptozotocin action in B cells of the rat pancreas. Physiological Research, 50(6), 537–546.
47. Taghizadeh M, Rashidi AA, Taherian AA, Vakili Z, Sajad Sajadian M, Ghardashi M, 2016. Antidiabetic and Antihyperlipidemic Effects of Ethanol Extract of Rosa canina L. fruit on Diabetic Rats: An Experimental Study With Histopathological Evaluations. Journal of Evidence-Based Complementary and Alternative Medicine, 21(4), NP25–NP
48. Tandogan B, Kuruüzüm-Uz A, Sengezer C, Güvenalp Z, Demirezer LÖ, Ulusu NN, 2011. In vitro effects of rosmarinic acid on glutathione reductase and glucose 6-phosphate dehydrogenase. Pharmaceutical biology, 49(6), 587–94.
49. Temel Y, Bozkuş T, Karagözoğlu Y, Çiftci M, 2017. Glutatyon Redüktaz ( GR ) Enziminin Japon Bıldırcın ( Coturnix coturnix japanica ) Eritrositlerinden Saflaştırılması ve Karakterizasyonu Purification and Characterization of Glutathion Reductase Enzyme From Japanese Quail (Coturnix coturnix japanica ). Iğdır Üniversitesi Fen Bilimleri Enstitüsü Dergisi, 7(3), 143-150.
50. Temel Y, Kocyigit UM, 2017. Purification of glucose-6-phosphate dehydrogenase from rat (Rattus norvegicus) erythrocytes and inhibition effects of some metal ions on enzyme activity. Journal of Biochemical and Molecular Toxicology, 31(9).
51. Temel Y, Kufrevioǧlu ÖI, Çiftci M, 2017. Investigation of the effects of purification and characterization of turkey (Meleagris gallopavo) liver mitochondrial thioredoxin reductase enzyme and some metal ions on enzyme activity. Turkish Journal of Chemistry, 41(1).
52. Temel Y, Bayındır S, 2019. The Synthesis of Thiosemicarbazone-Based Aza-Ylides as Inhibitors of Rat Erythrocyte Glucose 6-Phosphate Dehydrogenase Enzyme. Journal of the Institute of Science and Technology, 9(3), 1503–1512.
53. Temel Y, Koçyigit UM, Taysi MS, Gökalp F, Gürdere MB, Budak Y, Çiftci M, 2018. Purification of glutathione S-transferase enzyme from quail liver tissue and inhibition effects of (3aR,4S,7R,7aS)-2-(4-((E)-3-(aryl)acryloyl)phenyl)-3a,4,7,7a-tetrahydro-1H-4,7 methanoisoindole-1,3(2H)-dione derivatives on the enzyme activity. Journal of Biochemical and Molecular Toxicology.
54. Temel Y, Taysi MŞ, 2018. The Effect of Mercury Chloride and Boric Acid on Rat Erythrocyte Enzymes. Biological Trace Element Research, 177–182.
55. Türkan F, Huyut Z, Taslimi P, Huyut MT, Gülçin İ, 2020. Investigation of the effects of cephalosporin antibiotics on glutathione S-transferase activity in different tissues of rats in vivo conditions in order to drug development research. Drug and Chemical Toxicology, 43(4), 423–428.
56. Vianna R, Brault A, Martineau LC, Couture R, Arnason JT, Haddad P S, 2011. In vivo anti-diabetic activity of the ethanolic crude extract of Sorbus decora CK Schneid.(Rosacea): a medicinal plant used by Canadian James Bay Cree nations to treat symptoms related to diabetes. Evidence-Based Complementary and Alternative Medicine. https://doi.org/10.1093/ecam/nep158
57. Wang T, Fontenot RD, Soni MG, Bucci TJ, Mehendale HM, 2000. Enhanced hepatotoxicity and toxic outcome of thioacetamide in streptozotocin-induced diabetic rats. Toxicology and applied pharmacology,166: 92-100.
58. Yüzüak H, Aybak M, 2015. The possible protective effect of melatonin on streptozotocin induced experimental diabetes. Journal of Clinical and Experimental Investigations, 5(4), 592–598.
59. Zariç Y, 2018. Glutatyon S-transferaz enziminin Van Gölü inci kefali balığı (Chalcalburnus tarichi) solungacından saflaştırılması, karakterizasyonu, bazı metal ve pestisitlerin enzim aktivitesi üzerine etkilerinin incelenmesi (Master's thesis, Ağrı İbrahim Çeçen Üniversitesi, Fen Bilimleri Enstitüsü).