Kitosan Oligosakkarit (COS) Tedavisinin Oksidatif Stres Üzerine Etkileri ve Kadmiyuma Maruz Kalan Sıçanlarda Bağırsak Mikroflorası ile İlişkisi

Öz

Bu çalışmanın amacı, kronik olarak Cd’a maruz kalan ratlarda kitosan oligosakkarit’in (COS) oksidatif stress ve bağırsak mikroflorası üzerine etkilerinin araştırılmasıdır. Hayvanlar rastgele olacak şekilde; kontrol (C; n=8), kadmiyum (Cd; n=8), kitosan oligosakkarit (COS; n=8) ve kadmiyum+kitosan oligosakkarit (Cd+COS; n=8) gruplarına ayrıldı. Daha sonra, kadmiyum klorid (CdCl2) (2mg/kg/day) Cd ve Cd+COS gruplarındaki hayvanlara haftada 3 kez 4 hafta boyunca oral yoldan verildi. Kitosan oligosakkarit de (200 mg/kg/day) COS ve Cd+COS grubundaki hayvanlara haftada 5 kez 4 hafta boyunca oral olarak uygulandı. Deneme sonunda, serum TAS, TOS seviyeleri, plasma ALT, AST, GGT, T.pro, Alb, Bil, Creat ve BUN değerleri ölçüldü. Enterobacteriaceae, Lactococcus spp. ve Lactobacillus spp. sayılarıda belirlendi. Serum TOS seviyeleri Cd grubundaki hayvanlarda COS grubundakilere oranla önemli derecede yüksek bulundu (p <0,05). Cd grubundaki hayvanların ince bağırsaklarında, kronik Cd uygulaması Lactococcus spp. sayısında 0.66 log’lık bir düşüşe sebep oldu. Sonuç olarak, her iki bileşiğin antimikrobiyel etkinliği şelat oluşumuna bağlı olarak (COS-Cd) Cd+COS grubundaki hayvanlarda azalma gösterdi.          

Anahtar Kelimeler

• Kadmiyum,Kitosan oligosakkarit,mikroflora,oksidatif stres,rat

The Effects of Chitosan Oligosaccharide (COS) Treatment on Oxidative Stress and Its Relation with Intestinal Microflora in Rats Exposed To Cadmium

Öz

The aim of the study was to investigate the effects of chitosan oligosaccharide (COS) treatment on oxidative stress and its relation with intestinal microflora in rats exposed to chronic cadmium toxicity. Animals were randomly divided into four groups as control (C; n=8), cadmium (Cd; n=8), chitosan oligosaccharide (COS; n=8), cadmium+chitosan oligosaccharide (Cd+COS; n = 8). After, cadmium chloride (CdCl2) (2mg /kg/ day) was orally administered to Cd and Cd+COS groups three times a week for 4 weeks. Chitosan oligosaccharide (200 mg/kg/day) was also orally administered to COS and Cd+COS groups five times a week for 4 weeks. After completion of the experiment, serum TAS, TOS levels, plasma ALT, AST, GGT, T.pro, Alb, Bil, Creat and BUN values were measured. Enterobacteriaceae, Lactococcus spp. and Lactobacillus spp. counts were also detected. Serum TOS values were detected extremely higher in Cd group animals when compared COS group (p <0,05). In the small intestine of the Cd group animals, Cd administration caused a 0.66 log decrease in the Lactococcus spp. count. In conclusion, it was found that the antimicrobial effect of both compounds decreased as a result of COS-Cd chelating in Cd + COS group.

Anahtar Kelimeler

• Cadmium,chitosan oligosaccarides,microflora,oxidative stress,rat

Kaynakça

1. Agency for Toxic Substances and Disease Registry (ATSDR). Toxicological Profile for Cadmium ATSDR, Atlanta, Georgia (2008), p. 454.
2. Amamou F, Nemmiche S, Meziane RK, Didi A, Yazit SM, Chabane-Sari D. Protective effect of olive oil and colocynth oil against cadmiuminduced oxidative stress in the liver of Wistar rats. Food Chem Toxicol.2015;78:177-84.DOI: 10.1016/j.fct.2015.01.001. Amato SM, Orman MA, Brynildsen MP. Metabolic control of persister formation in Escherichia coli. Mol Cell. 2013; 50(4): 475-487. DOİ: 10.1016/j.molcel.2013.04.002.
3. Baselt, RC, Cravey RH. Disposition of Toxic Drugs and Chemicals in Man. 4th Edn. Chicago,IL: Year Book Medical Publishers; 1995. pp. 105-107.
4. Bauer TM, Fernández J, Navasa M, Vila J, Rodés J. Failure of Lactobacillus spp. to prevent bacterial translocation in a rat model of experimental cirrhosis. J Hepatol, 2002; 36(4), 501-506. DOI:10.1016/S0168-8278(02)00003-X.
5. Bernhoft RA. Cadmium toxicity and treatment. Sci.World J.2013:394652. DOİ:10.1155/2013/394652.
6. Costello EK, Stagaman K, Dethlefsen L, Bohannan BJ, Relman DA. The application of ecological theory toward an understanding of the human microbiome. Science. 2012; 336(6086):1255-1262. DOİ: 10.1126/science.1224203.
7. Djurasevic S, Jama A, Jasnic N, Vujovic P, Jovanovic M, Mitic-Culafic D, Knezevic-Vukcevic J, Cakic-Milosevic M, Ilijevic K, Djordjevic J. The Protective Effects of Probiotic Bacteria on Cadmium Toxicity in Rats. J Med Food. 2017; 20(2):189-196. DOI: 10.1089/jmf.2016.0090.
8. El-Boshy ME, Risha EF, Abdelhamid FM, Mubarak MS, Hadda TB. Protective effects of selenium against cadmium induced hematological disturbances, immunosuppressive, oxidative stress and hepatorenal damage in rats. J Trace Elem Med Biol. 2014; 29: 104-10. DOİ:10.1016/j.jtemb.2014.05.009.

9. El-Demerdash FM, Yousef MI, Kedwany FS, Baghdadi HH. Cadmium-induced changes in lipid peroxidation, blood hematology, biochemical parameters and semen quality of male rats: protective role of vitamin E and beta-carotene. Food Chem Toxicol. 2004; 42(10):1563-1571. DOI: 10.1016/j.fct.2004.05.001
10. Erel O. A new automated colorimetric method for measuring total oxidant status. Clin biochem. 2005; 38(12): 1103-1111. DOI: 10.1016/j.clinbiochem.2005.08.008
11. Erel O. A novel automated direct measurement method for total antioxidant capacity using a new generation, more stable ABTS radical cation. Clin biochem. 2004; 37: 277-285. DOI: 10.1016/j.clinbiochem.2003.11.015.
12. Fang C. Characterization of Polyphenol Oxidase and Antioxidants From Pawpaw (Asimina Tribola) Fruit. 2007; University of Kentucky Master's Theses 477. https://uknowledge.uky.edu/gradschool_theses/477.
13. Fazeli M, Hassanzadeh P, Alaei S. Cadmium chloride exhibits a profound toxic effect on bacterial microflora of the mice gastrointestinal tract. Hum Exp Toxicol. 2011; 30(2): 152-159. DOI: 10.1177/096032711036982.
14. Fowler BA. Monitoring of human populations for early markers of cadmium toxicity: A review. Toxicol Applied Pharma. 2009; 238(3): 294–300. DOI: 10.1016/j.taap.2009.05.004.
15. Gao D, Xu Z, Kuang X, Qiao P, Liu S, Zhang L, He P, Jadwiga WS, Wang Y, Min W. Molecular characterization and expression analysis of the autophagic gene beclin 1 from the purse red common carp (Cyprinus carpio) exposed to cadmium. Comp Biochem Physiol C Toxicol Pharmacol. 2014; 160:15-22.
16. Guan G., Wang H., Chen S., Liu G., Xiong X., Tan B., Duraipandiyan V, Al-Dhabi NA, Fang J. Dietary chitosan supplementation increases microbial diversity and attenuates the severity of Citrobacter rodentium infection in mice. Mediat Inflamm. 2016:9236196. DOI:10.1155/2016/9236196.
17. Hamden K, Allouche N, Damak M, Elfeki A. Hypoglycemic and antioxidant effects of phenolic extracts and purified hydroxytyrosol from olive mill waste in vitro and in rats. Chem Biol Interact. 2009;180(3):421-32. DOİ: 10.1016/j.cbi.2009.04.002. Hammett-Stabler CA. Disposition of Toxic Drugs and Chemicals in Man, 5th ed. R.C. Baselt. Foster City, CA: Chemical Toxicology Institute, 1999, 900 pp., $119.00. ISBN 0-9626523-3-4. Published June 2000.
18. Hsueh PR, Badal RE, Hawser SP, Hoban DJ, Bouchillon SK, Ni Y, Paterson DL. Epidemiology and antimicrobial susceptibility profiles of aerobic and facultative gram-negative bacilli isolated from patients with intra-abdominal infections in the Asia-Pacific region: 2008 results from SMART (Study for Monitoring Antimicrobial Resistance Trends). Int J Antimicrob Agents. 2010:36(5):408–414. DOI: 10.1016/j.ijantimicag.2010.07.002.
19. Hussein SA, Abd-el-maksoud HA, Agag BI, El-nile MB. Effect of cadmium toxicity on some biochemical blood parameters and their modulation with certain natural antioxidants in rabbits. Benha Ras Surd. 2009; 338–62.
20. Ibiam AU, Ugwuja EI, Ejeogo C, Ugwu O. Cadmium-Induced Toxicity and the Hepatoprotective Potentials of Aqueous Extract of Jessiaea Nervosa Leaf. Adv Pharm Bull. 2013; 3(2), 309-313. DOİ: 10.5681/apb.2013.050
21. Inaba T1, Kobayashi E, Suwazono Y, Uetani M, Oishi M, Nakagawa H, Nogawa K. Estimation of cumulative cadmium intake causing Itai-itai disease. Toxicol Lett. 2005; 159: 192-201. DOI: 10.1016/j.toxlet.2005.05.011
22. Inglin RC, Stevens MJ, Meile L, Lacroix C, Meile L. High-throughput screening assays for antibacterial and antifungal activities of Lactobacillus species. J Microbiol Methods. 2015; 114:26-29. DOI: 10.1016/j.mimet.2015.04.011.
23. International Agency for Research on Cancer (IARC). Cadmium and cadmium compounds. IARC Monogr Eval Carcinog Risks Hum. 1993; 58: 119-237.
24. ISO 21528-2:2017. Microbiology of the food chain — Horizontal method for the detection and enumeration of Enterobacteriaceae — Part 2: Colony-count technique
25. Jean SS, Coombs G, Ling T, Balaji V, Rodrigues C, Mikamo H, Kim MJ, Rajasekaram DG, Mendoza M, Tan TY1, Kiratisin P1, Ni Y1, Weinman B, Xu Y, Hsueh PR. Epidemiology and antimicrobial susceptibility profiles of pathogens causing urinary tract infections in the Asia-Pacific region: results from the study for monitoring antimicrobial resistance trends (SMART), 2010-2013. Int J Antimicrob. Agents. 2016; 47(4):328-34. DOI: 10.1016/j.ijantimicag.2016.01.008.
26. 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
27. Kim KN, Joo ES, Kim KI, Kim, SK, Yang HP, Jeon YJ. Effect of chitosan oligosaccharides on cholesterol level and antioxidant enzyme activities in hypercholesterolemic rat. J Korean Soc Food Sci Nutr. 2005; 34(1):36-41. DOİ:10.3746/jkfn.2005.34.1.036.
28. Kim MY, Shon WJ, Park MN, Lee YS, Shin DM. Protective effect of dietary chitosan on cadmium accumulation in rats. Nutr Res Pract. 2016; 10(1):19-25. DOİ:10.4162/nrp.2016.10.1.19
29. Koçak M, Akçil E. The effects of chronic cadmium toxicity on the hemostatic system. Pathophysiol Haemost Thromb. 2006; 35(6): 411-416. DOI: 10.1159/000102047
30. Kumas M, Esrefoglu M, Bayindir N, Iraz M, Ayhan S, Meydan S. Protective Effects of Curcumin on Cadmium-Induced Renal Injury in Young and Aged Rats. Bezmialem Science. 2016; 3: 92-8. DOI: 10.14235/bs.2016.788
31. Lai CC, Chen CC, Huang HL, Chuang YC, Tang HJ. The role of doxycycline in the therapy of multidrug-resistant E. coli - an in vitro study. Sci. Rep. 2016; 6:31964. DOI: 10.1038/srep31964.
32. Lakshmi GD, Kumar PR, Bharavi K, Annapurna P, Rajendar B, Patel PT, Kumar CS, Rao GS. Protective effect of Tribulus terrestris linn on liver and kidney in cadmium intoxicated rats. Indian J Exp Biol. 2012; 50(2): 141-146.
33. Lee, K. C., Liu, C. F., Lin, T. H., and Pan, T. M. Safety and risk assessment of the genetically modified Lactococci on rats intestinal bacterial flora. Int J Food Microbiol. 2010; 142, 164–169. DOI: 10.1002/iub.1027
34. Li R, Zhou Y, Ji J, Wang L. Oxidative damages by cadmium and the protective effects of low-molecular-weight chitosan in the freshwater crab (Sinopotamon yangtsekiense Bott 1967). Aquac Res. 2011; 42(4):506-515. DOİ: 10.1111/j.1365-2109.2010.02646.x.
35. López E, Arce C, Oset-Gasque MJ, Cañadas S, González MP. Cadmium induces reactive oxygen species generation and lipid peroxidation in cortical neurons in culture. Free Radical Biol Med.2006;40(6):940-951. DOI: 10.1016/j.freeradbiomed.2005.10.062
36. Markiewicz-Górka I1, Zawadzki M, Januszewska L, Hombek-Urban K, Pawlas K. Influence of selenium and/or magnesium on alleviation alcohol induced oxidative stress in rats, normalization function of liver and changes in serum lipid parameters. Hum Exp Toxicol. 2011; 30(11): 1811-1827. DOI: 10.1177/0960327111401049.
37. Monachese M, Burton JP, Reid G. Bioremediation and tolerance of humans to heavy metals through microbial processes: a potential role for probiotics? Appl Environ Microbiol. 2012; 78 (18): 6397–6404. DOI: 10.1128/AEM.01665-12.
38. Monteiro MP, Batterham RL. The Importance of the Gastrointestinal Tract in Controlling Food Intake and Regulating Energy Balance. Gastroenterology. 2017; 52(7):1707-1717. DOİ: 10.1053/j.gastro.2017.01.053.
39. Naveed M, Phil L, Sohail M, Hasnat M, Baig MMFA, Ihsan AU, Shumzaid M, Kakar MU, Khan TM, Akabar MD, Hussainc MI, Zhou QG. Chitosan oligosaccharide (COS): An overview. Int J Biol Macromol. 2019; 129:827-843. DOI: 10.1016/j.ijbiomac.2019.01.192.
40. Oyinloye BE, Ajiboye BO, Ojo OA, Musa HM, Onikanni SA, Ojo AA. Ameliorative potential of Aframomum melegueta extract in cadmium- induced hepatic damage and oxidative stress in male Wistar rats. J Appl Pharm Sci. 2016; 6(7):94-99. DOİ: 10.7324/JAPS.2016.60714.
41. Paschal DC, Burt V, Caudill SP, Gunter EW, Pirkle JL, Sampson EJ, Miller DT, Jackson RJ. Exposure of the USA population aged 6 years and older to cadmium. 1988-1994. Arch Environ Contam Toxicol. 2000; 38(3):377-83. DOI: 10.1007/s002449910050.
42. 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.
43. Ralitsa G, Lyubomira Y, Lilia T, Galina Z, Nina S, Akseniya A, Antonia D, Gergana I, Nikolay K, Nevenka R, Elena K. Antimicrobial activity and antibiotic susceptibility of Lactobacillus and Bifidobacterium spp. intended for use as starter and probiotic cultures. Biotechnol Biotechnol Equip. 2015; 29(1): 84-91. DOİ:10.1080/13102818.2014.987450.
44. Renugadevi J, Milton prabu S. Quercetin protects against oxidative stress-related renal dysfunction by cadmium in rats. Exp Toxicol Pathol. 2010; 62(5): 471–81. DOİ:10.1016/j. etp.2009.06.006.
45. Salim SY, Jovel J, Wine E, Kaplan GG, Vincent R, Thiesen A, Barkema HW, Madsen KL. Exposure to ingested airborne pollutant particulate matter increases mucosal exposure to bacteria and induces early onset of inflammation in neonatal IL-10-deficient mice. Inflamm Bowel Dis. 2014;20(7):1129-38. DOİ: 10.1097/MIB.0000000000000066.
46. Satarug S, Baker JR, Urbenjapol S, Haswell-Elkins M, Reilly PE, Williams DJ, Moore MR. A global perspective on cadmium pollution and toxicity in non-occupationally exposed population. Toxicol Lett.2003;137(1-2):65-83. DOİ:10.1016/S0378-4274(02)00381-8.
47. Satarug S, Garrett SH, Sens MA, Sens DA. Cadmium, environmental exposure, and health outcomes. Cien Saude Colet. 2011;16(5): 2587-2602. DOI: 10.1289/ehp.0901234.
48. Smith GM, White CL. A molybdenum–sulfur–cadmium interaction in sheep. Aust. J. Agric. Res. 1997; 48(2): 147-154. DOI:10.1071/A96092.
49. Tannock IF. Methotrexate and mitomycin for patients with metastatic transitional cell carcinoma of the urinary tract. Cancer Treat Rep. 1983; 67 (5): 503-504.
50. Tchounwou PB, Yedjou CG, Patlolla AK, Sutton DJ. Heavy Metals Toxicity and the Environment. EXS. 2012; 101:133-164. DOİ:10.1007/978-3-7643-8340-4_6.
51. Toh HS1, Chuang YC, Huang CC, Lee YL, Liu YM, Ho CM, Lu PL, Liu CE, Chen YH, Wang JH, Ko WC, Yu KW, Liu YC, Chen YS, Tang HJ, Hsueh PR. Antimicrobial susceptibility profiles of gram-negative bacilli isolated from patients with hepatobiliary infections in Taiwan: results from the study for monitoring antimicrobial resistance trends (SMART), 2006-2010. Int J Antimicrob Agents. 2012; 40S1: S18–S23. DOI: 10.1016/S0924-8579(12)70005-5.
52. Toz H, Değer Y. The Effect of Chitosan on the Erythrocyte Antioxidant Potential of Lead Toxicity-Induced Rats. Biol Trace Elem Res. 2018; 184(1):114-118. DOI: 10.1007/s12011-017-1164-2
53. Upreti RK, Shrivastava R, Chaturvedi UC. Gut microflora & toxic metals: chromium as a model. Indian J Med Res. 2004; 119: 49–59.
54. Wang J, Zhang C, Guo C, Li X. Chitosan Ameliorates DSS-Induced Ulcerative Colitis Mice by Enhancing Intestinal Barrier Function and Improving Microflora. Int. J. Mol. Sci. 2019; 20(22): E5751. DOI: 10.3390/ijms20225751.
55. Woodmansey EJ. Intestinal bacteria and ageing. J Appl Microbiol. 2007; 102: 1178-1186. DOİ:10.1111/j.1365-2672.2007.03400.x
56. World Health Organization (WHO). Exposure to Cadmium: A Major Public Health Concern. World Health Organization, 2010; 3–6. http://www.who.int/ipcs/features/cadmium.pdf.
57. Yan Y, Wanshun L, Baoqin H, Bing L, Chenwei F. Protective effects of chitosan oligosaccharide and its derivatives against carbon tetrachloride-induced liver damage in mice. Hepatol Res. 2006; 35:178-184. DOI: 10.1016/j.hepres.2006.04.001.
58. Zhang P, Liu W, Peng Y, Han B, Yang Y. Toll like receptor 4 (TLR4) mediates the stimulating activities of chitosan oligosaccharide on macrophages. Int Immunopharmacol. 2014; 23(1): 254-261. DOI: 10.1016/j.intimp.2014.09.007.
59. Zhou Y, Gao B, Zimmerman AR, Fang J, Sun Y, Cao X. Sorption of heavy metals on chitosan-modified biochars and its biological effects. Chem Eng J. 2013; 231:512–518. DOI: 10.1016/j.cej.2013.07.036.
60. Zohouri A, Tekeli SK. Ratlarda Kadmiyumun Metabolizma Üzerindeki Etkilerinin Araştırılması. Istanbul Üniv Vet Fak Derg. 1999; 25(2): 261–71.