Melatonin Uygulamasının Kronik Kadmiyum Toksikasyonuna Maruz Kalan Sıçanlarda Bazı Serum İmmun-Regülatör Sitokinler Üzerine Etkisi

Öz

Bu çalışmada kronik kadmiyum toksikasyonuna maruz kalan sıçanlarda melatonin’in bazı serum immun-regülatör sitokin seviyeleri üzerine etkilerinin araştırılması amaçlanmıştır. Bu amaç doğrultusunda, hayvanlar (n =32); kontrol grubu (K) kadmiyum grubu (Cd), melatonin grubu (Mlt) ve kadmiyum + melatonin grubu (CdMlt) olmak üzere rastgele dört eşit gruba ayrıldı. Cd ve CdMlt gruplarındaki hayvanlara, 4 hafta boyunca haftada üç kez gastrik gavaj yoluyla oral kadmiyum klorür (CdCl2) (2 mg/kg/gün) verildi. Öte yandan Mlt ve CdMlt gruplarına 4 hafta boyunca haftada beş kez oral Mlt (100 mg/ kg/gün) uygulaması yapıldı. Kontrol grubunda yer alan sıçanlara herhangi bir uygulama yapılmadı. Deney periyodundan sonra, sıçanlar sakrifiye edildi ve kan örnekleri antikoagulant içermeyen tüplere alındı. Deneme sonunda serum IL-1β, IL-2, IL-6, TNF-α ve INFγ konsantrasyonları belirlendi. IL-1β, IL-2 ve IL-6 seviyelerinde deney grupları arasında bir değişiklik bulunmadı (p >0,05). Ayrıca, Mlt uygulaması CdMlt grubundaki TNF-α düzeylerini Cd grubuna kıyasla iyileştirdi (p <0,05). IFNγ seviyeleri Cd grubu ile karşılaştırıldığında en yüksek oranda C ve Mlt gruplarında tespit edildi (p<0,05). Sonuç olarak, Mlt uygulaması Cd toksisitesine maruz kalan sıçanlarda sadece TNF-α düzeylerinde önemli bir değişikliğe neden olmuştur.

Anahtar Kelimeler

• Kadmiyum
• melatonin
• serum
• sitokin
• sıçan

The Effects Of Melatonin Treatment On Some Serum Immunoregulatory Cytokine Levels In Rats Exposed To Chronic Cadmium Toxicity

Öz

The present study aimed to investigate the effect of melatonin treatment on some serum immunoregulatory cytokine levels in rats exposed to chronic cadmium toxicity. For this purpose, animals (n = 32) were divided randomly into four equal groups as untreated control (C), cadmium (Cd), melatonin (Mlt) and Cd + Mlt (CdMlt). The rats in Cd and CdMlt groups received cadmium chloride (CdCl2) (2 mg/kg/day) orally by gastric gavage three times a week for 4 weeks. On the other hand, Mlt (100 mg/kg/day) was orally administrated to Mlt and CdMlt groups five times a week for 4 weeks. C group was not received any treatment. After the treatments, the animals were sacrificed and blood samples were taken to without anticoagulant tubes. Then, levels of IL-1β, IL-2, IL- 6, TNF-α, and INFγ in the serum were determined. It was not found any change among the groups according to IL-1β, IL-2, and IL-6 levels (p>0,05). Besides, the administration of Mlt ameliorated the TNF-α levels in CdMlt group compared to Cd (p<0,05). IFNγ levels were found the highest in C and Mlt groups compared to Cd (p<0,05). In conclusion, Mlt treatment caused a significant change only in TNF-α levels in rats exposed to Cd.

Anahtar Kelimeler

• Cadmium
• cytokine
• melatonin
• serum
• rat

Kaynakça

1. Afolabi OK, Oyewo EB, Adekunle AS, Adedosu OT, Adedeji AL. Impaired Lipid Levels and Inflammatory Response in Rats Exposed to Cadmium. EXCLI J. 2012; 11: 677-687. ISSN 1611-2156.
2. Alghasham A, Salem TA, Meki AM. Effect of cadmium-polluted water on plasma levels of tumor necrosis factor-a, interleukin-6 and oxidative status biomarkers in rats: Protective effect of curcumin. Food Chem Toxicol. 2013; 59: 160-164. DOI: 10.1016/j.fct.2013.05.059.
3. Almenara CCP, Broseghini-Filho GB, Vescovi MVA, Angeli JK, Faria TO, Stefanon I, Vassallo DV, Padilha AS. Chronic Cadmium Treatment Promotes Oxidative Stress and Endothelial Damage in Isolated Rat Aorta. PLoS One. 2013; 8(7): e68418. DOI: 10.1371/journal.pone.0068418.
4. Bali I, Bilir B, Emir S, Turan F, Yılmaz A, Gökkuş T, Aydın M. The effects of melatonin on liver functions in arsenic-induced liver damage. Ulus Cerrahi Derg. 2016; 32: 233-237. DOI: 10.5152/UCD.2015.3224.
5. Broncel M, Koziróg-Kołacińska M, Chojnowska-Jezierska J. Melatonin in the treatment of atherosclerosis. Pol Merkur Lekarski. 2007; 23(134):124-7.
6. Cuypers A, Plusquin M, Remans T, Jozefczak M, Keunen E, Gielen H, Opdenakker K, Nair AR, Munters E, Artois TJ, Nawrot T, Vangronsveld J, Smeets K. Cadmium stress: an oxidative challenge. Biometals. 2010; 23: 927-940. DOI: 10.1007/s10534-010-9329-x.
7. Dan Z, Yong M, Sujuan D, Jiang H, Fang J. Effects of Melatonin on Intestinal Microbiota and Oxidative Stress in Colitis Mice. BioMed Res Int. 2018. ID 2607679:6. DOI: https://doi.org/10.1155/2018/2607679.
8. Dinarello CA. Interleukin-1. Cytokine and Growth Factor Reviews. 1997; 8(4): 253-265. DOI: 10.1016/s1359-6101(97)00023-3.

9. Đukic-Cosic D, Baralic K, Javorac D, Djordjevic AB, Bulat Z. An overview of molecular mechanisms in cadmium toxicity. Curr Opin Toxicol. 2020; 19: 56-62. DOI: https://doi.org/10.1016/j.cotox.2019.12.002.
10. Durappanavar PN, Nadoor P, Waghe P, Pavithra BH, Jayaramu GM. Melatonin Ameliorates Neuropharmacological and Neurobiochemical Alterations Induced by Subchronic Exposure to Arsenic in Wistar Rats. Biol Trace Elem Res. 2019;190:124-139. DOI: https://doi.org/10.1007/s12011-018-1537-1.
11. Dutta S, Saha S, Mahalanobish S, Sadhukhan P, Sil PC. Melatonin attenuates arsenic induced nephropathy via the regulation of oxidative stress and inflammatory signaling cascades in mice. Food Chem Toxicol. 2018; 118: 303-316. DOI: 10.1016/j.fct.2018.05.032.
12. Haddadi GH, Fardid R. Oral administration of melatonin modulates the expression of tumor necrosis factor-α (TNF-α) gene in irradiated rat cervical spinal cord. Rep Pract Oncol Radiother. 2015; 20(2):123-7. DOI: 10.1016/j.rpor.2014.11.003.
13. Hirano T. Interleukin 6 and its Receptor: Ten Years Later. Int Rev Immunol. 1998; 16: 3-4. DOI: 10.3109/08830189809042997.
14. International Agency for Research on Cancer. Cadmium and cadmium compounds. In: Arsenic, metals, fibres and dusts. A review of human carcinogens. IARC Monographs 100C, pp 121–145. IARC, Lyon (2012), France.
15. Karabulut-Bulan O, Bolkent S, Yanardag R, Bilgin-Sokmen B. The role of vitamin C, vitamin E, and selenium on cadmium-induced renal toxicity of rats. Drug Chem Toxicol. 2008; 31(4): 413–26. DOI: 10.1080/01480540802383200.
16. Karbownik M, Lewinski A, Reiter RJ. Anticarcinogenic actions of melatonin which involve antioxidative processes: comparison with other antioxidants. Int J Biochem Cell Biol. 2001; 33: 735-53. DOI: 10.1016/s1357-2725(01)00059-0.
17. Kataranovski M, Kataranovski D, Savic D, Jovcic G, Bogdanovic Z, Jovanovic T. Granulocyte and plasma cytokine activity in acute cadmium intoxication in rats. Physiol Res. 1998; 47: 453.
18. Kim Y, Ahn Y, Kim J. Infuence of melatonin on immunotoxicity of cadmium. Int Immunopharmacol. 2000; 22: 275-284. DOI: 10.1016/s0192-0561(99)00082-x.
19. Kisadere I, Donmez N. The effects of quercetin on antioxidant system and some blood parameters in rats exposed to acute cadmium toxicity. Eurasian J Vet Sci. 2019; 35 (2): 66-70. DOI: 10.15312/EurasianJVetSci.2019.22.
20. Kisadere I, Donmez N, Donmez HH. The effects of quercetin on antioxidant and cytokine levels in rat hippocampus exposed to acute cadmium toxicity. J Cell Neurosci Oxid Stress. 2019; 11(0): 10-10. DOI: 10.37212/jcnos.584684.
21. Klassen CD, Liu J, Diwan BA. Metallothionein protection of cadmium toxicity. Toxicol Appl Pharmacol. 2009; 238: 215-220. DOI: 10.1016/j.taap.2009.03.026.
22. Krocova Z, Macela A, Kroca M, Hernychova L. The immunomodulatory effect(s) of lead and cadmium on the cells of immune system in vitro. Toxicol In Vitro. 2000; 14: 33. DOI: 10.1016/s0887-2333(99)00089-2.
23. Li R, Luo X, Li L, Peng Q, Yang Y, Zhao L, Ma M, Hou Z. The Protective Effects of Melatonin Against Oxidative Stress and Inflammation Induced by Acute Cadmium Exposure in Mice Testis. Biol Trace Elem Res. 2016; 170:152-164. DOI: 10.1007/s12011-015-0449-6.
24. Maestroni GJM. Therapeutic Potential of Melatonin in Immunodeficiency States, Viral Diseases, and Cancer. Adv Exp Med Biol. 1999; 467: 217-26. DOI: 10.1007/978-1-4615-4709-9_28.
25. Marth E, Jelovcan S, Kleinhappl B, Gutschi A, Barth S. The effect of heavy metals on the immune system at low concentrations. Int J Occup Med Environ Health. 2001; 14 (4): 375-386.
26. Moniuszko-Jakoniuk J, Jurczuk M, Gałażyn-Sidorczuk M. Evaluation of Some Immunoregulatory Cytokines in Serum of Rats Exposed to Cadmium and Ethanol. Polish J Environ Stud. 2009; 18 (4): 673-680.
27. Patra RC, Rautray AK, Swarup D. Oxidative Stress in Lead and Cadmium Toxicity and Its Amelioration. Vet Med Int. 2011; 2011: 457327. DOI: 10.4061/2011/457327.
28. Pourmorad F, Hosseinimehr SJ, Shahabimajd N. Antioxidant activity, phenol and flavonoid contents of some selected Iranian medicinal plants. Afr J Biotechnol. 2006; 5 (11): 1142–45. DOI:10.1055/s-2007-987042.
29. Predes FDS, Diamante MAS, Dolder H. Testis response to low doses of cadmium in Wistar rats. Int J Exp Path. 2010; 91: 125-131. DOI: 10.1111/j.1365-2613.2009.00692.x
30. Shin I, Shin N, Park J, Jeon C, Hong J, Kwon O, Kim J, Lee I, Kim J, Oh S, Ahn K. Melatonin Attenuates Neutrophil Inflammation and Mucus Secretion in Cigarette Smoke-Induced Chronic Obstructive Pulmonary Diseases via the Suppression of Erk-Sp1 Signaling. J Pineal Res. 2015; 58(1):50-60. DOI: 10.1111/jpi.12192. Epub 2014 Nov 29.
31. Srinivasan V, Maestroni GJM, Cardinali DP, Esquifino AI, Perumal SRP, Miller SC. Melatonin, Immune Function and Aging. Immun Ageing. 2005;29(2):17. DOI: 10.1186/1742-4933-2-17. DOI: 10.1186/1742-4933-2-17.
32. Szuster-Ciesielska A, Łokaj I, Kandefer-Szerszeń M. The influence of cadmium and zinc ions on the interferon and tumor necrosis factor production in bovine aorta endothelial cells. Toxicol. 2000; 145 (2-3): 135-145. DOI: 10.1016/s0300-483x(00)00147-5.
33. Taga T, Kishimoto T. GP130 and the Interleukin-6 family of cytokines. Annu Rev Immunol. 1997; 15: 797-819. DOI: 10.1146/annurev.immunol.15.1.797.
34. Turley AE, Zagorski JW, Kennedy RC, Freeborn RA, Bursley JK, Edwards JR, Rockwell CE. Chronic Low-Level Cadmium Exposure in Rats Affects Cytokine Production by Activated T Cells. Toxicol Res. 2019; 8(2):227-237. DOI: 10.1039/c8tx00194d.
35. Ware CF, VanArsdale S, VanArsdale TL. Apoptosis mediated by the TNF‐related cytokine and receptor families. J Cell Biochem. 1996; 60: 47-55. DOI: 10.1002/(SICI)1097-4644(19960101)60:1%3C47::AID-JCB8%3E3.0.CO;2-3.
36. Yucesoy B, Turhan A, Ure M, Imir T, Karakaya A. Effects of occupational lead and cadmium exposure on some immunoregulatory cytokine levels in man. Toxicol. 1997; 123: 143-147. DOI: 10.1016/s0300-483x(97)00107-8.
37. Zhang J, An J. Cytokines, Inflammation and Pain. Int Anesthesiol Clin. 2007; 45(2): 27-37. DOI:10.1097/AIA.0b013e318034194e.