Ratlarda Kadmiyum Kaynaklı Mide Toksisitesine Karşı Karvakrol’un Etkileri

Öz

Sunulan çalışmanın amacı; ağır metallerden olan kadmiyumun (Cd) neden olduğu mide toksisitesine karşı karvakrol (Krv)’nin etkilerinin araştırılmasıdır. Çalışmada Spraque Dawley cinsi 35 adet erkek rat rastgele 5 gruba ayrıldı: Kontrol grubu, Cd uygulanan grup, Krv 50 mg kg-1 uygulanan grup, Cd + Krv 25 mg kg-1 uygulanan grup ve Cd + Krv 50 mg kg-1 uygulanan grup. Cd’nin glutatyon peroksidaz (GPx), süperoksit dismutaz (SOD) ve katalaz (KAT) gibi antioksidan enzim aktivitelerini ve glutatyon (GSH) düzeylerini azaltıp, lipid peroksidasyonunu (LPO) artırarak oksidatif hasara neden olduğu belirlendi. Ayrıca Cd ile kombine uygulanan Krv uygulamasının GSH seviyesini ve antioksidan enzim aktivitelerini arttırdığı, lipid peroksidasyonunu ise azalttığı tespit edildi. Çalışmada incelenen glikoz düzenleyici protein 78 (GRP78) mRNA transkipt seviyesinin Cd grubunda önemli şekilde arttığı, Krv uygulamasının ise bu gene ait ekspresyon seviyesini azalttığı belirlendi. Mide dokusunda Cd toksikasyonu aktive edici transkripsiyon faktör 6 (ATF6) ekspresyonunu arttırdığı, Krv uygulaması ile bu gene ait ekspresyonda düşüş meydana geldiği saptandı.
Sonuç olarak; Cd kaynaklı mide toksisitesinde Krv’nin yararlı etkilerinin olduğu oksidan-antioksidan denge ile GRP78 ve ATF6 ekspresyonları incelenerek tespit edildi.

Anahtar Kelimeler

• Kadmiyum,Karvakrol,Mide,Oksidatif stres

Effects of Carvacrol Against Cadmium-Induced Stomach Toxicity in Rats

Abstract

The aim of this study is investigation of the effects of carvacrol (Crv) against stomach toxicity caused by cadmium (Cd), which is a heavy metal. In the study, 35 male rats of Spraque Dawley were randomly divided into 5 groups: the control group, the group that received Cd, the group recevied Crv 50 mg kg-1, the group that received Cd + Crv 25 mg kg-1, and the group that received Cd + Crv 50 mg kg-1. It has been determined that Cd causes oxidative damage by decreasing antioxidant enzyme activities such as glutathione peroxidase (GPx), superoxide dismutase (SOD) and catalase (CAT), and increasing lipid peroxidation (LPO). In addition, it was found that Crv administration combined with Cd increased GSH level and antioxidant enzyme activities and decreased lipid peroxidation. It was determined that the level of glucose regulated protein 78 (GRP78) mRNA transcript examined in the study increased significantly in the Cd group, while Crv application decreased the expression level of this gene. It was determined that Cd toxicity in the stomach tissue increased activating transcription factor 6 (ATF6) expression and that the expression of this gene decreased with the recevied of Crv.
As a result, it has been determined by examining the oxidant-antioxidant balance with GRP78 and ATF6 expressions that Crv has beneficial effects on Cd-induced stomach toxicity.

Keywords

• Cadmium,Carvacrol,Stomach,Oxidative stress

Kaynakça

1. [1] Rahman Z, Singh VP. The relative impact of toxic heavy metals (THMs)(arsenic (As), cadmium (Cd), chromium (Cr)(VI), mercury (Hg), and lead (Pb)) on the total environment: an overview. Environ Monit Assess. 2019; 191.7: 419.
2. [2] El-Boshy M, Ashshi A, Gaith M, Qusty N, Bokhary T, AlTaweel N, et al. Studies on the protective effect of the artichoke (Cynara scolymus) leaf extract against cadmium toxicity-induced oxidative stress, hepatorenal damage, and immunosuppressive and hematological disorders in rats. Environ Sci Pollut Res Int. 2017;24(13):12372-12383.
3. [3] Haouem S, El Hani A. Effect of cadmium on lipid peroxidation and on some antioxidants in the liver, kidneys and testes of rats given diet containing cadmium-polluted radish bulbs. J Toxicol Patho. 2013; 26.4: 359-364.
4. [4] Kriegel AM, Soliman AS, Zhang Q, Ghawalby NE, Ezzat F, Soultan A et al. Serum cadmium levels in pancreatic cancer patients from the East Nile Delta region of Egypt Environ Health Perspect. 2006; 114.1: 113-119.
5. [5] Naglaa E. Effect of Aqueous Extract of Glycyrrhiza glabra on the Biochemical Changes Induced by Cadmium Chloride in Rats. Biol. Trace Elem. Res. 2019;190(1):87-94.
6. [6] Alaei P, Khodarahmi P, Salehipour M. Effect of repeated injection of cadmium on Bax/Bcl-2 mRNA Level in stomach of rats. Int J Med Sci. 2018;5(2):133-140.
7. [7] Saleh RM, Awadin WF. Biochemical and histopathological changes of subacute cadmium intoxication in male rats. Environ Sci Pollut Res Int 2017;24(32):25475-25481.
8. [8] Wardani G, Eraiko K, Sudjarwo SA. Protective activity of chitosan nanoparticle against cadmium chloride induced gastric toxicity in rat. J Young Pharm 2018;10(3):303.

9. [9] Haze K, Yoshida H, Yanagi H, Yura T, Mori K. Mammalian transcription factor ATF6 is synthesized as a transmembrane protein and activated by proteolysis in response to endoplasmic reticulum stress. Mol Biol Cell. 1999;10(11), 3787-3799.
10. [10] Xu X, Lei T, Li W, & Ou H. Enhanced cellular cholesterol efflux by naringenin is mediated through inhibiting endoplasmic reticulum stress-ATF6 activity in macrophages. Biochim Biophys Acta. 2019; 1864.10: 1472-1482.
11. [11] Aksu EH, Kandemir FM, Altun S, Küçükler S, Çomaklı S, Ömür AD. Ameliorative effect of carvacrol on cisplatin‐Induced reproductive damage in male rats. J Biochem Mol Toxic 2016;30(10):513-520.
12. [12] Kim KS, Lim H-J, Lim JS, Son JY, Lee J, Lee BM, et al. Curcumin ameliorates cadmium-induced nephrotoxicity in Sprague-Dawley rats. Food Chem Toxicol 2018;114:34-40.
13. [13] Bayramoglu G, Senturk H, Bayramoglu A, Uyanoglu M, Colak S, Ozmen A, et al. Carvacrol partially reverses symptoms of diabetes in STZ-induced diabetic rats. Cytotechnology, 2014; 66(2), 251-257.
14. [14] Placer ZA, Cushman LL, Johnson BC. Estimation of product of lipid peroxidation (malonyl dialdehyde) in biochemical systems. Anal. Biochem. 1966;16(2):359-364.
15. [15] Sedlak J, Lindsay RH. Estimation of total, protein-bound, and nonprotein sulfhydryl groups in tissue with Ellman's reagent. Anal. Biochem. 1968;25:192-205.
16. [16] Matkovics B. Determination of enzyme activity in lipid peroxidation and glutathione pathways. Laboratoriumi Diagnosztika 1988;15:248-250.
17. [17] Sun Y, Oberley LW, Li Y. A simple method for clinical assay of superoxide dismutase. Clin. Chem. 1988;34(3):497-500.
18. [18] Aebi H. Methods in enzymology. vol. 105. Packer, ed., Academic, NY 1984:121-126.
19. [19] [19] Lowry OH, Rosebrough NJ, Farr AL, Randall RJ. Protein measurement with the Folin phenol reagent. J Biol Chem 1951;193:265-275.
20. [20] Livak KJ, Schmittgen TD. Analysis of relative gene expression data using real-time quantitative PCR and the 2− ΔΔCT method. methods 2001;25(4):402-408.
21. [21] Sarwar N, Malhi SS, Zia MH, Naeem A, Bibi S, Farid G. Role of mineral nutrition in minimizing cadmium accumulation by plants. J. Sci. Food Agric. 2010;90(6):925-937.
22. [22] Kandemir FM, Yıldırım S, Kucukler S, Caglayan C, Darendelioğlu E, Dortbudak MB. Protective effects of morin against acrylamide-induced hepatotoxicity and nephrotoxicity: A multi-biomarker approach. Food Chem Toxicol 2020;138:111190.
23. [23] Kandemir FM, Caglayan C, Aksu EH, Yildirim S, Kucukler S, Gur C, et al. Protective effect of rutin on mercuric chloride‐induced reproductive damage in male rats. Andrologia 2020.
24. [24] Çelik H, Kandemir FM, Caglayan C, Özdemir S, Çomaklı S, Kucukler S et al. Neuroprotective effect of rutin against colistin-induced oxidative stress, inflammation and apoptosis in rat brain associated with the CREB/BDNF expressions. Mol. Biol. Rep. 2020;47(3):2023-2034.
25. [25] Temel Y, Kucukler S, Yıldırım S, Caglayan C, Kandemir FM. Protective effect of chrysin on cyclophosphamide-induced hepatotoxicity and nephrotoxicity via the inhibition of oxidative stress, inflammation, and apoptosis. Naunyn Schmiedebergs Arch. Pharmacol. 2020;393(3):325-337.
26. [26] Çelik H, Kucukler S, Çomaklı S, Özdemir S, Caglayan C, Yardım A, et al. Morin attenuates ifosfamide-induced neurotoxicity in rats via suppression of oxidative stress, neuroinflammation and neuronal apoptosis. NeuroToxicology 2020;76:126-137.
27. [27] Caglayan C, Kandemir FM, Darendelioğlu E, Yıldırım S, Kucukler S, Dortbudak MB. Rutin ameliorates mercuric chloride-induced hepatotoxicity in rats via interfering with oxidative stress, inflammation and apoptosis. J Trace Elem Med Bio 2019;56:60-68.
28. [28] Sakat MS, Kilic K, Kandemir FM, Yildirim S, Sahin A, Kucukler S, et al. The ameliorative effect of berberine and coenzyme Q10 in an ovalbumin-induced allergic rhinitis model. Eur Arch Otorhinolaryngol 2018;275(10):2495-2505.
29. [29] Aksu EH, Kandemir FM, Yıldırım S, Küçükler S, Dörtbudak MB, Çağlayan C, et al. Palliative effect of curcumin on doxorubicin‐induced testicular damage in male rats. J Biochem Mol Toxic 2019;33(10):e22384.
30. [30] Kandemir FM, Kucukler S, Çağlayan C. Ratlarda Methotrexate Kaynaklı Karaciğer Toksisitesine Karşı Silymarin ve Naringin’in Yararlı Etkileri. Atatürk Üniversitesi Veteriner Bilimleri Dergisi 2017;12(2):167-177.
31. [31] Patra R, Rautray AK, Swarup D. Oxidative stress in lead and cadmium toxicity and its amelioration. J. Vet. Med. Sci. 2011;2011.
32. [32] Nair AR, DeGheselle O, Smeets K, Van Kerkhove E, Cuypers A. Cadmium-induced pathologies: where is the oxidative balance lost (or not)? Int J Mol Sci 2013;14(3):6116-6143.
33. [33] Kandemir FM, Yildirim S, Caglayan C, Kucukler S, Eser G. Protective effects of zingerone on cisplatin-induced nephrotoxicity in female rats. Environ Sci Pollut Res Int 2019;26(22):22562-22574.
34. [34] Kuzu M, Yıldırım S, Kandemir FM, Küçükler S, Çağlayan C, Türk E, et al. Protective effect of morin on doxorubicin-induced hepatorenal toxicity in rats. Chem. Biol. Interact. 2019;308:89-100.
35. [35] Singh P, Mogra P, Bano H, Sankhla V, Deora K, Barolia S, et al. Protective and preventive effects of curcumin against cadmium chloride induced gastrointestinal toxicity in Swiss albino mice. World j. sci. technol. 2012;2(12):10-17.
36. [36] de Oliveira Leite G, Penha ARS, da Silva GQ, Colares AV, Rodrigues FFG, Costa JGM, et al. Gastroprotective effect of medicinal plants from Chapada do Araripe, Brazil. J Young Pharm 2009;1(1):54.
37. [37] Rebelo FM, Caldas ED. Arsenic, lead, mercury and cadmium: Toxicity, levels in breast milk and the risks for breastfed infants. Environ. Res. 2016;151:671-688.
38. [38] Nwokocha C, Nwokocha M, Owu D, Edidjana E, Nwogbo N, Ekpo U, et al. Estimation of absorbed cadmium in tissues of male and female albino rats through different routes of administration. Niger. J. Physiol. Sci. 2011;26(1).
39. [39] Patrick L. Toxic metals and antioxidants: part II. The role of antioxidants in arsenic and cadmium toxicity. Altern Med Rev 2003;8(2).
40. [40] Caglayan C, Kandemir FM, Yildirim S, Kucukler S, Eser G. Rutin protects mercuric chloride‐induced nephrotoxicity via targeting of aquaporin 1 level, oxidative stress, apoptosis and inflammation in rats. J Trace Elem Med Bio 2019;54:69-78.
41. [41] Hanedan B, Ozkaraca M, Kirbas A, Kandemir FM, Aktas MS, Kilic K, et al. Investigation of the effects of hesperidin and chrysin on renal injury induced by colistin in rats. Biomed Pharmacother 2018;108:1607-1616.
42. [42] Aksu EH, Kandemir FM, Küçükler S, Mahamadu A. Improvement in colistin‐induced reproductive damage, apoptosis, and autophagy in testes via reducing oxidative stress by chrysin. J Biochem Mol Toxic 2018;32(11):e22201.
43. [43] Gobe G, Crane D. Mitochondria, reactive oxygen species and cadmium toxicity in the kidney. Toxicol. Lett. 2010;198(1):49-55.
44. [44] Rasheva VI, Domingos PM. Cellular responses to endoplasmic reticulum stress and apoptosis. Apoptosis 2009;14(8):996-1007.
45. [45] Greenblatt D, Wygnanski I. Effect of leading-edge curvature on airfoil separation control. J. Aircr. 2003;40(3):473-481.
46. [46] Chou X, Ding F, Zhang X, Ding X, Gao H, Wu Q. Sirtuin-1 ameliorates cadmium-induced endoplasmic reticulum stress and pyroptosis through XBP-1s deacetylation in human renal tubular epithelial cells. Arch. Toxicol. 2019;93(4):965-986.
47. [47] Jin Y, Zhang S, Tao R, Huang J, He X, Qu L, et al. Oral exposure of mice to cadmium (II), chromium (VI) and their mixture induce oxidative‐and endoplasmic reticulum‐stress mediated apoptosis in the livers. Environ. Toxicol. 2016;31(6):693-705.
48. [48] Ekinci Akdemir FN, Yildirim S, Kandemir FM, Tanyeli A, Küçükler S, Bahaeddin Dortbudak M. Protective effects of gallic acid on doxorubicin-induced cardiotoxicity; an experimantal study. Arch Physiol Biochem 2019:1-8.
49. [49] Kilic K, Sakat MS, Yildirim S, Kandemir FM, Gozeler MS, Dortbudak MB et al. The amendatory effect of hesperidin and thymol in allergic rhinitis: an ovalbumin-induced rat model. Eur Arch Otorhinolaryngol 2019;276(2):407-415.
50. [50] Eki̇nci̇-Akdemi̇r FN, Yildirim S, Kandemi̇r FM, Gülçi̇n İ, Küçükler S, Sağlam YS, et al. The effects of casticin and myricetin on liver damage induced by methotrexate in rats. Iran J Basic Med Sci 2018;21(12):1281.