Kadmiyuma Maruz Kalan Ratlarda Oral Melatonin Uygulamasının Oksidatif Stres ve Bağırsak Mikroflorası Üzerine Etkisi

Year 2020, Volume: 31 Issue: 2, 111 - 116, 03.07.2020

Hakan Tavşanlı , İhsan Kısadere

https://doi.org/10.36483/vanvetj.685081

Abstract

Bu çalışmanın amacı, kronik kadmiyuma maruz kalan ratlarda oral melatonin uygulamasının, oksidatif stres ve bağırsak mikroflorasında bulunan bazı mikroorganizmalar üzerine etkilerini araştırmaktır. Sağlıklı 32 yetişkin erkek albino Wistar rat, kontrol (C; n=8), kadmiyum (Cd; n=8), melatonin (Mlt, n=8), kadmiyum + melatonin (Cd + Mlt; n=8) olarak rastgele dört gruba ayrılmıştır. Ratlara oral yolla Mlt (100 mg/kg), (Cd ve Cd + Mlt) haftada 5 kez (Mlt ve Cd + Mlt) ve CdCl2 (2 mg/gün) 3 kez olmak üzere 4 hafta boyunca uygulanmıştır. Uygulamadan sonra serum total antioksidan seviyeleri (TAS), total oksidan (TOS) düzeyleri ile plazma ALT, AST, GGT, T.pro, Alb ve BUN değerleri ölçülmüştür. Ayrıca ince ve kalın bağırsak içerikleri ayrı ayrı aseptik olarak alınarak bağırsak florasında Enterobacteriaceae, Lactococcus spp. ve Lactobacillus spp. sayımları yapılmıştır. Bulgu olarak, serum TOS düzeyleri Cd grubunda diğer gruplara göre daha yüksek olarak tanımlanmıştır (P <0,05). Cd grubunda ince bağırsak florasında Lactococcus spp. sayısı C grubuna göre 0,63 log azalırken, Cd + Mlt grubunda 1,15 log artmıştır. Sonuç olarak, Cd + Mlt şelatının Enterobacteriaceae üremesini baskılanması, Lactobacillus spp./Lactococcus spp. oranını düzenlemesi ve Cd’a bağlı gelişen oksidatif stresi azaltması nedeni ile intestinal mikroflora için faydalı olabilir.

Keywords

Kadmiyum, Melatonin, Mikroflora, Oksidatif Stres, Rat

Influence of oral melatonin administration on oxidative stress and intestinal microflora in rats exposed to cadmium

Abstract

The aim of the present study was to evaluate the effects of oral melatonin treatment on oxidative stress and intestinal microflora in rats exposed to chronic cadmium. Healthy 32 adult male albino Wistar rats were randomly divided into four groups as control (C; n=8), cadmium (Cd; n=8), melatonin (Mlt, n=8), cadmium + melatonin (Cd + Mlt; n=8). Mlt (100 mg/kg) was orally administered 5 times (Mlt and Cd + Mlt), and CdCl2 (2 mg/day) 3 times a week for 4 weeks to rats (Cd and Cd + Mlt). After the treatments, serum total antioxidant status (TAS), total oxidant (TOS) levels as well as plasma ALT, AST, GGT, T.pro, Alb and BUN values were measured. Intestinal contents were aseptically collected, and Enterobacteriaceae, Lactococcus spp. and Lactobacillus spp. counts were performed. As a result, serum TOS levels were defined higher in Cd group than other groups (P <0.05). Lactococcus spp. counts decreased as 0.63 log in Cd group compared to C in small intestine, however it increased as 1.15 log in Cd + Mlt group. In conclusion, Cd + Mlt chelate was found benefical for intestinal microflora due to suppressed the Enterobacteriaceae growth, however ameliorated the Cd induced oxidative stress and Lactobacillus spp./Lactococcus spp. rates in the different part of the intestine.

Keywords

cadmium, melatonin, microflora, oxidative stress

References

• Agency for Toxic Substances and Disease Registry (ATSDR) (1999). Toxicology profile for cadmium. Atlanta, GA: Department of Health and Human Services, Public Health Service; p. 258.
• Alabbassi MG, Hussain SA, Shatha HA (2008). Therapeutic effects of melatonin in lead-ınduced toxicity in rats. Iraqi J Pharm Sci, 17, 47-54.
• Andjelkovic M, Djordjevic AB, Antonijevic E, Antonijevic B, et al. (2019). Toxic effect of acute cadmium and lead exposure in rat blood, liver, and kidney. Int J Environ Res, 16(2), 274.
• Bauer TM, Fernández J, Navasa M, Vila J, et al. (2002). Failure of Lactobacillus spp. to prevent bacterial translocation in a rat model of experimental cirrhosis. J hepatol, 36(4), 501-506.
• Bengmark S (1998). Ecological control of the gastrointestinal tract. The role of probiotic flora. Gut 42, 2-7.
• Bu T, Mi Y, Zeng W, Zhang C (2013). Protective effect of quercetin on cadmium-induced oxidative toxicity on germ cells in male mice. Anat Rec, 294 (3), 520-26.
• Chweatiuk E, Wostowski T, Krasowska A, Bonda E (2006). The effect of orally administered melatonin on tissue accumulation and toxicity of cadmium in mice. J Trace Elem Med Biol 19, 259-265.
• Cook CM, Sgardelis SP, Pantis JD, Lanaras T (1994). Concentrations of Pb, Zn, and Cu in Taraxacum spp. in relation to urban pollution. Bull Environ Contam Toxicol, 53, 204-210. Zhu D, Ma Y, Ding S, Jiang H, (2018). Effects of melatonin on ıntestinal microbiota and oxidative stress in colitis mice. BioMed Res Int, Article ID 2607679, 6.
• Djurasevic S, Jama A, Jasnic N, et al (2016). The protective effects of probiotic bacteria on cadmium toxicity in rats. J Med Food, 00 (0), 1-8.
• Eckburg PB, Bik EM, Bernstein CN, et al. (2005). Diversity of the human intestinal microbial flora. Science, 308,1635-1638.
• El-boshy ME, Risha EF, Abdelhamid FM, et al. (2014). Protective effects of selenium against cadmium induced hematological disturbances, immunosuppressive, oxidative stress and hepatorenal damage in rats. J Trace Elem Med Biol, 29, 104-10.
• El-Sokkary GH, Nafady AA, Shabash EH (2009). Melatonin ameliorates cadmium-ınduced oxidative damage and morphological changes in the kidney of rat. The Open Neuroendocrin J, 2, 1-9 1.
• Erel O (2005). A new automated colorimetric method for measuring total oxidant status. Clin biochem, 38, 1103-1111.
• Erel O (2004). A novel automated direct measurement method for total antioxidant capacity using a new generation, more stable ABTS radical cation. Clin biochem, 37, 277-285.
• Eybl V, Kotyzova D, Koutensky J (2006). Comparative study of natural antioxidants - curcumin, resveratrol and melatonin- in cadmium-induced oxidative damage in mice. Toxicology, 225, 150-6.
• Fang C (2007). Characterization of polyphenol oxidase and antioxidants from pawpaw ( asimina tribola) fruit. University of Kentucky Master's Theses 477.
• Fazeli M, Hassanzadeh P, Alaei S (2011). Cadmium chloride exhibits a profound toxic effect on bacterial microflora of the mice gastrointestinal tract. Hum Exp Toxicol, 30, 152.
• Figueiredo-Pereira ME, Yakushin S, Cohen G (1998). Disruption of the Intracellular Sulfhydryl Homeostasis by Cadmium-induced Oxidative Stress Leads to Protein Thiolation and Ubiquitination in Neuronal Cells. J Biol Chem, 273 (21), 12703-12709.
• Fowler BA (2009). Monitoring of human populations for early markers of cadmium toxicity: A review. Toxicol Applied Pharma, 238, 294-300.
• Gerhardsson LLU, Englyst V, Lundstrom NG, et al. (2002). Cadmium, copper and zinc in tissues of deceased copper smelter workers. J Trace Elem Med Biol, 16(4), 261-66. Glombitza F (2001). Treatment of acid lignite mine flooding water by means of microbial sulfate reduction. Waste Manag, 21, 197-203.
• Goyer RA (1986). Toxic effects of metals. In: Klassen CD, Amdur MO, Doull J, editors. Casarett and Doull’stoxicology. Macmillan Publishing p.592–6. New York.
• Hooper LV, Wong MH, Thelin A et al. (2001). Molecular analysis of commensal hostmicrobial relationships in the intestine. Science 2: 881–884.
• Hussein SA, Abd-el-maksoud HA, Agag BI, El-nile MB (2009). Effect of cadmium toxicity on some biochemical blood parameters and their modulation with certain natural antioxidants in rabbits. Benha Ras Surd, 338-62.
• Hussein SA, Hassanein MRR, Ali AH (2014). Protective effects of alpha-lipoic acid against lead-induced oxidative stress in erythrocytes of rats. Benha Vet Med J, 27(2), 382-395. Inaba T, Kobayashi E, Suwazono Y et al. (2005). Estimation of cumulative cadmium intake causing Itai-itai disease. Toxicol Lett, 159, 192-201.
• Kanter M, Unsal C, Aktas C, Erboga M (2013). Neuroprotective effect of quercetin against oxidative damage and neuronal apoptosis caused by cadmium in hippocampus. Toxicol Ind Health 32(3), 541-50.
• Kaplan M, Atakan IH, Aydoğdu N, et al. (2008). Influence of N-acetylcysteine on renal toxicity of cadmium in rats. Pediatr Nephrol, 23, 233-41.
• Karabulut-bulan O, Bolkent S, Yanardag R (2008). The role of vitamin C, vitamin E, and selenium on cadmium-induced renal toxicity of rats. Drug Chem Toxicol, 31(4), 413-26.
• Karbownik M, Gitto E, Lewinski A, Reiter RJ (2001). Induction of lipid peroxidation in hamster organs by the carcinogen cadmium: melioration by melatonin. Cell Biol Toxicol, 17, 33-40.
• Kısadere I, Donmez N (2019). The effects of quercetin on antioxidant system and some blood parameters in rats exposed to acute cadmium toxicity. Eurasian J Vet Sci, 35 (2), 66-70.
• Kocak M, Akcil E (2006). The effects of chronic cadmium toxicity on the hemostatic system. Pathophysiol Haemost Thromb, 35(6), 411-16.
• Kostecka-Sochoń P, Onopiuk BM, Dąbrowska E (2018). Protective Effect of Increased Zinc Supply against Oxidative Damage of Sublingual Gland in Chronic Exposure to Cadmium: Experimental Study on Rats. Oxidative Medicine and Cellular Longevity Volume 2018; Article ID 3732842, 8 pages.
• Kumas M, Esrefoglu M, Bayindir N et al. (2016). Protective Effects of Curcumin on Cadmium-Induced Renal Injury in Young and Aged Rats. Bezmialem Science 3, 92-8.
• Lakshmi GD, Kumar PR, Bharavi K et al. (2012). Protective effect of Tribulus terrestris linn on liver and kidney in cadmium intoxicated rats. Indian J Exp Biol, 50, 141-146.
• Lee KC, Liu CF, Lin TH, Pan TM (2010). Safety and risk assessment of the genetically modified Lactococci on rats intestinal bacterial flora. Int J Food Microbiol, 142(1-2), 164-169.
• Marrero J, Gonza´lez LJ, Sa´nchez A et al. (2004). Effect of high concentration of Co (II) on Enterobacter liquefaciens strain C-1: a bacterium highly resistant to heavy metals with an unknown genome. Proteomics, 4, 1265-1279.
• Monachese M, Burton JP, Reid G (2012). Bioremediation and tolerance of humans to heavy metals through microbial processes: a potential role for probiotics? Appl Environ Microbiol, 78, 6397-6404.
• Osman N, Adawi D, Molin G et al. (2006). Bifidobacterium infantis strains with and without a combination of oligofructose and inulin (OFI) attenuate inflammation in DSS-induced colitis in rats. Bmc Gastroenterology 6(1): 31.
• Oyinloye BE, Ajiboye BO, Ojo OA et al. (2016). Ameliorative potential of Aframomum melegueta extract in cadmium- induced hepatic damage and oxidative stress in male Wistar rats. J Appl Pharm Sci, 6, 94-99.
• Pourmorad F, Hosseinimehr SJ, Shahabimajd N (2006). Antioxidant activity, phenol and flavonoid contents of some selected Iranian medicinal plants. Afr J Biotechnol, 5 (11), 1142-45.
• Reiter RJ, Tan DX, Osuna C, Gitto E (2000). Actions of melatonin in the reduction of oxidative stress. A review. J Biomed Sci, 7, 444-58.
• Renugadevi J, Milton prabu S (2010). Quercetin protects against oxidative stress-related renal dysfunction by cadmium in rats. Exp Toxicol Pathol 62(5), 471, 81.
• Satarug S, Baker JR, Urbenjapol S et al. (2003). A global perspective on cadmium pollution and toxicity in non-occupationally exposed population. Toxicol Lett, 137(1-2), 65-83.
• Satarug S, Garrett SH, Sens MA, Sens DA (2010). Cadmium, environmental exposure, and health outcomes. Environ Health Perspect, 118, 182-190.
• Shagirtha K, Muthumani M, Prabu SM (2011). Melatonin abrogates cadmium induced oxidative stress related neurotoxicity in rats. Eur Rev Med Pharmacol Sci, 15, 1039-1050.
• Tancrede C (1992). Role of human microflora in health and disease. Eur J Clin Microbiol Infect Dis, 11, 1012-1015.
• Upreti RK, Shrivastava R, Chaturvedi UC (2004). Gut microflora & toxic metals: chromium as a model. Indian J Med Res, 119, 49-59.
• WHO (World Health Organization) (1993). Evaluation of certain food additives and contaminants, Fortyfirst Report of the Joint FAO/WHO Expert Committee on Food Additives. Technical Report 837.
• Zohouri A, Tekeli SK (1999). Ratlarda Kadmiyumun Metabolizma Üzerindeki Etkilerinin Araştırılması. Istanbul Üniv Vet Fak Derg 25(2), 261-71.