Kadmiyum Uygulanan Farelerde Oluşturulan Oksidatif Strese Karşı Resveratrolün Koruyucu Etkisinin Araştırılması*

Year 2020, , 215 - 220, 01.12.2020

Canan Işık Bircan Oğuz Merhan

https://doi.org/10.32707/ercivet.828324

Cited By: 4

Abstract

Kadmiyum ve diğer ağır metaller hem çevresel hem de mesleki maruziyetlerle insan sağlığını tehdit etmekte ve sanayide yaygın olarak kullanılmaktadır. Resveratrol anti-inflamatuvar, antioksidan, antitümör ve immunomodulatör özellikleri olan doğal bir polifenolik bileşiktir. Bu nedenle yapılan çalışmada farelerin plazma, karaciğer, böbrek ve kalp dokusunda kadmiyum toksisitesine karşı resveratrolün koruyucu etkisi araştırılmıştır. Çalışmada 35 fare eşit olarak 5 gruba ayrılmıştır. Kontrol grubu, alkol grubu, kadmiyum grubu (CdCl2, 1 mg/kg/gün), resveratrol grubu (10 mg/kg/gün), kadmiyum+resveratrol grubu (1 mg/kg/gün+10 mg/kg/gün) olarak belirlenmiştir. Tüm uygulamalar 21 gün süreyle oral gavaj yoluyla uygulanmıştır. Uygulama süresi sonunda karaciğer, böbrek ve kalp dokusunda oksidatif stresin gösterge-si olarak malondialdehit (MDA) ve nitrik oksit (NO) miktarları, antioksidan savunmanın biyobelirteci olarak redükte glu-tatyon (GSH) miktarı, akut faz yanıtın bir göstergesi olan total siyalik asit (TSA) ve plazmada aspartat aminotransferaz (AST), alanin aminotransferaz (ALT), gamma glutamil transpeptidaz (GGT) aktiviteleri spektrofotometrik yöntemlerle belirlenmiştir. Kontrole göre, kadmiyum verilen grupta doku (karaciğer, böbrek ve kalp) MDA, NO, TSA düzeyleri ile plazma AST, ALT, GGT aktiviteleri önemli derecede artarken, doku GSH düzeyi ise önemli derecede azalmıştır. Kad-miyum+resveratrol verilen grupta ise doku MDA, NO, TSA düzeyleri ile plazma AST, ALT, GGT aktivitelerinin kadmi-yum verilen gruba göre istatistiksel olarak önemli derecede azalırken, doku GSH düzeyi ise önemli derecede artmıştır. Sonuç olarak kadmiyumun toksik etkisine karşı resveratrolün karaciğer, böbrek ve kalpte koruyucu etkisinin olabileceği kanısına varılmıştır.

Keywords

Kadmiyum, oksidatif stres, resveratrol, siyalik asit

The Investigation of the Protective Effect of Resveratrol on Oxidative Stress Levels in Mice Given Cadmium

Abstract

Cadmium and other heavy metals which are commonly used in industry could threaten human health with both environmental and occupational exposures. Resveratrol, a natural polyphenol, is thought to have some properties such as anti-inflammatory, antioxidant, antitumor and immunomodulatory. Therefore, the present study was designed to examine the protective effect of resveratrol on cadmium toxicity in plasma, liver, kidney and heart tissue of mice. In our study, thirty five mice were equally divided into five groups. Control group, alcohol group, cadmium group (CdCl2, 1 mg/kg/day), resveratrol group (10 mg/kg/day), cadmium+resveratrol group (1 mg/kg/day+10 mg/kg/day). All treatments were administered orally via gavage for 21 days. The amount of malondialdehyde (MDA) and nitric oxide (NO) as an indicator of oxidative stress in liver, kidney, and heart tissue at the end of the application period, the amount of reduced glutathione (GSH) as a biomarker of antioxidant defense, total sialic acid (TSA) as an indicator of acute phase respon-se and aspartate aminotransferase (AST), alanine aminotransferase (ALT), gamma glutamyl transpeptidase (GGT) activities in plasma were determined by spectrophotometric methods. In cadmium group, it was determined that tissue MDA, NO, TSA level and plasma AST, ALT, GGT activities increased significantly compared to control in the tissue (liver, kidney, and heart), while tissue GSH level decreased significantly compared to control. In cadmium+resveratrol group, it was determined that tissue MDA, NO, TSA level and plasma AST, ALT, GGT activities decreased, while tis-sue GSH level increased statistically significantly compared to cadmium groups. As a result, it was concluded that res-veratrol may have a protective effect on the liver, kidney and heart against the toxic effect of cadmium.

Keywords

Cadmium, oxidative stress, resveratrol, sialic acid

References

• Atakisi E, Merhan O. Nitric oxide synthase and nitric oxide involvement in different toxicities. Saravi SSS. ed. In: Nitric Oxide Synthase-Simple Enzy-me-Complex Roles. Croatia: In Tech 2017; pp. 197-214.
• Bagchi D, Bagchi M, Hassoun EA, Stohs SJ. Cad-mium-induced excretion of urinary lipid metaboli-tes, DNA damage, glutathione depletion, and he-patic lipid peroxidation in Sprague-Dawley rats. Biol Trace Elem Res 1996; 52(2): 143-54.
• Beutler E, Duron O, Kelly BM. Improved method for the determination of blood glutathione. J Lab Clin Med 1963; 61: 882-8.
• Coyle P, Niezing G, Shelton TL, Philcox JC, Rofe AM. Tolerance to cadmium hepatotoxicity by me-tallothionein and zinc: In vivo and in vitro studies with MT-null mice. Toxicol 2000; 150(1-3): 53-67.
• Das DK, Maulik N. Resveratrol in cardioprotection: a therapeutic promise of alternative medicine. Mol Interv 2006; 6(1): 36-47.
• El-Demerdash FM, Yousef MI, Kedwany FS, Baghda-di HH. Cadmium-induced changes in lipid peroxi-dation, blood hematology, biochemical parame-ters and semen quality of male rats: Protective role of vitamin E and beta-carotene. Food Chem Toxicol 2004; 42(10): 1563-71.
• El-Ebiary AA, El-Ghaiesh S, Hantash E, Alomar S. Mitigation of cadmium-induced lung injury by Nigella sativa oil. Environ Sci Poll Res 2016; 23(24): 25356-63.
• Giovannini L, Migliori M, Longoni BM, Das DK, Ber-telli AA, Panichi V, Filippi C, Bertelli A. Resverat-rol, a polyphenol found in wine, reduces ischemia reperfusion injury in rat kidneys. J Cardiovasc Pharmacol 2001; 37(3): 262-70.
• Gross SS, Wolin MS. Nitric oxide: Pathophysiological mechanisms. Annu Rev Physiol 1995; 57: 737-69.
• Kim BM, Lee SY, Jeong IH. Influence of squid liver powder on accumulation of cadmium in serum, kidney and liver of mice. Prev Nutr Food Sci 2013; 18(1): 1-10.
• Kishimoto T, Oguri T, Ohno M, Matsubara K, Yama-moto K, Tada M. Effect of cadmium (CdCl2) on cell proliferation and production EDRF (endothelium-derived relaxing factor) by cultured human umbilical arterial endothelial cells. Arch Toxicol 1994; 68(9): 555-9.
• Koyu A, Gökçimen A, Özgüner F, Bayram DS, Kocak A. Evaluation of the effects of cadmium on rat liver. Mol Cell Biochem 2006; 284(1-2): 81-5.
• Li Y, Cao Z, Zhu H. Upregulation of endogenous anti-oxidants and phase 2 enzymes by the red wine polyphenol, resveratrol in cultured aortic smooth muscle cells leads to cytoprotection against oxi-dative and electrophilic stres. Pharmacol Res 2006; 53(1): 6-15.
• Lindberg G, Eklund GA, Gullberg B, Rastam L. Se-rum sialic acid concentration and cardiovascular mortality. BMJ 1991; 302(6769): 143-6.
• Merhan O, Özcan A. Kazlarda serum seruloplazmin ve total sialik asit düzeylerinin araştırılması. Kafkas Univ Vet Fak Derg 2004; 10(2): 139-42.
• Miranda KM, Espey MG, Wink DA. A rapid, simple spectrophotometric method for simultaneous de-tection of nitrate and nitrite. Nitric Oxide 2001; 5(1): 62-71.
• Pratt DS, Kaplan MM. Evaluation of abnormal liver enzyme results in asymptomatic patients. N Engl J Med 2000; 342(17): 1266-71.
• Renugadevi J, Prabu SM. Naringenin protects aga-inst cadmium-induced oxidative renal dysfunction in rats. Toxicology 2009; 256(1-2): 128-34.
• Sarkar S, Yadav P, Trivedi R, Bansal AK, Bhatnagar D. Cadmium-induced lipid peroxidation and the status of the antioxidant system in rat tissues. J Trace Elem Med Biol 1995; 9(3): 144-9.
• Sener G, Toklu HZ, Sehirli AÖ, Velioglu-Ögünç A, Çetinel S, Gedik N. Protective effects of resverat-rol against acetaminophen-induced toxicity in mice. Hepatol Res 2006; 35(1): 62-8.
• Shiraishi N, Rehm S, Waalkes MP. Effect of chlorpro-mazine pretreatment on cadmium toxicity in the male wistar (WF/NCr) rat. J Toxicol Environ Health 1994; 42(2): 193-208.
• Skoczynska A, Martynowicz H. The impact of subch-ronic cadmium poisoning on the vascular effect of nitric oxide in rats. Hum Exp Toxicol 2005; 24(7): 353-61.
• Skowerski M, Jasik K, Konecki J. Effects of interac-tion between cadmium and selenium on heart metabolism in mice: the study of m RNA, protein, ANP synthesis activities and ultrastructure in mo-use heart. Med Sci Monit 2000; 6(2): 258-65.
• Sydow G. A simplifield quick method for determina-tion of sialic acid in serum. Biomed Biochim Acta 1985; 44(11-12): 1721-3.
• Tomera JF, Kukulka SP, Lilford K, Harakal C. Cad-mium accumulation in experimental hypertension. Corn Art Dis 1991; 2: 769-74.
• Tsuruoka S, Sugimoto KI, Muto S, Nomiyama K, Fujimura A, Imai M. Acut effect of cadmium-metallothionein on glucose and amino acid trans-port across the apical membrane of the rabbit proximal tubule perfused in vitro. J Pharmacol Exp Ther 2000; 292(2): 769-77.
• Vorobieva RS, Eremeeva EP. Cardiovascular fuction in workers exposed to cadmium. Gig Sanit 1980; 10: 22-5.
• Wang B, Du Y. Cadmium and its neurotoxic effects. Oxid Med Cell Longev 2013; 2013: 1-12.
• Yoshioka T, Kawada K, Shimada T, Mori M. Lipid peroxidation in maternal and cord blood and pro-tective mechanism against activated-oxygen toxicity in the blood. Am J Obstet Gynecol 1979; 135(3): 372-6.
• Yousef M, Vlachogiannis IA, Tsiani E. Effects of res-veratrol against lung cancer: In vitro an in vivo studies. Nutrients 2017; 9(11): 1-14.