Effect the some heavy metals on carbonic anhydrase enzymes activities from non-tumour and tumour human stomach

Year 2015, Volume: 1 Issue: 1, 25 - 28, 20.05.2015

Emrah Yerlikaya Ramazan Demirdağ , Ömer Küfrevioğlu , Cemal Gündoğdu

Abstract

In this study, in vitro effects of certain heavy metals on the human carbonic anhydrase enzyme were examined. Inhibitory effects of metal ions ( Pb²⁺, Cu²⁺, Fe²⁺,Cr²⁺, Al³⁺, Ni²⁺, Mn²⁺, Cd²⁺, Zn²⁺, and Mg²⁺) were observed in tumour and non-tumour tissue. IC₅₀ values were calculated for metals. The Cu²⁺, Zn²⁺, Ni²⁺, Cd²⁺ and Mg²⁺ IC₅₀ values of tumour tissue were calculated as 0.034mM, 0.426mM, 0.597mM, 0.878mM and 2.52mM respectively. The Cu²⁺, Zn²⁺, Ni²⁺, Cd²⁺ and Mg²⁺  IC₅₀ values of non-tumour tissue were calculated as 0.067mM, 0.991mM, 1.065mM, 1.724mM and 6.13mM respectively. Carbonic anhydrase activity was measured as described by Wilbur and Anderson. Hydratase activity was used to determine IC₅₀ values. In this study, tumour and non-tumour human stomach tissue was selected due to the fact that among the diseases, stomach cancer has one of the highest mortality rates. Stomach cancer, a type of cancer effecting the digestive system, is a fatal disease in living systems.  The effects of metals on the CA enzyme were investigated due to the extremely important role that CA enzymes play in living beings.

Keywords

-

References

• . Wang B, Xu D, Yu X, Ding T, Rao H, Zhan Y, Zheng L, Li L. Association of intra-tumoural infiltrating macrophages and regulatory T cells is an independent prognostic factor in gastric cancer after radical resection. Ann Surg Oncol. 2011; 18: 2585-2593.
• . Winaver SJ. Gastric cancer. Worldwide burden and prevention opportunities. Chinese journal of Digestive Disease. 2005; 6: 107-109.
• . Ekinci D, Cavdar H, Talaz O, Senturk M, Supuran CT. NO-releasing esters show carbonic anhydrase inhibitory action against human isoforms I and II. Bioorg Med Chem. 2010; 18:3559-63.
• . Hilvo M, Tolvanen M, Clark A, Shen BR, Shah GN, Waheed A, Halmi P, Hanninen M, Hamalainen JM, Vihinen M, Sly WS, Parkkila S. Characterization of CA XV, a new GPI anchored form of carbonic anhydrase. Biochem J. 2005; 392: 83-92.
• . Ekinci D, Beydemir S, Kufrevioglu OI. In vitro inhibitory effects of some heavy metals on human erythrocyte carbonic anhydrases. J Enzym Inhib Med Ch. 2007; 22: 745-50.
• . Ozensoy O, Supuran CT. Carbonic anhydrase IX as prognostic marker for tumor progression and as a target for novel antitumor drugs. Turk J Biochem. 2007; 32: 130-134.
• . Ceyhun SB, Senturk M, Yerlikaya E, Erdogan O, Kufrevioglu OI, Ekinci D. Purification and characterization of carbonic anhydrase from the teleost fish dicentrarchus labrax (european seabass) liver and toxicological effects of metals on enzyme activity. Environ Toxicol Pharm. 2011; 32: 69-74.
• . Hura C, Hura BA. Assessment of the heavy metals in the food from Romania, 2005. Toxicology Letters 2006; 164:270.
• . Arora M, Kiran B, Rani S, Rani A, Kaur B, Mittal N. Heavy metal accumulation in vegetables irrigated with water from different sources. Food Chemistry. 2008; 111: 811-815.
• . Demirdag R, Yerlikaya E, Kufrevioglu O.I and Gundogdu C. Purification of glutathione S-transferase isoenzymes from tumour and non-tumour human stomach and inhibitory effects of some heavy metals on enzymes activities. J Enzym Inhib Med Ch. 2012. DOI: 10.3109/14756366.2012.694878.
• . Wilbur KM, Anderson NG. Electrometric and colorimetric determination of carbonic anhydrase. J Biol Chem. 1948; 176: 147-154.
• . Demirdag R, Comakli V, Senturk M, Ekinci D, Kufrevioglu OI, Supuran CT. Purification and characterization of carbonic anhydrase from sheep kidney and influences of sulfonamides on enzyme activity. Bioorg Med Chem. 2012; http://dx.doi.org/10.1016/j.bmc.2012.08.018
• . Senturk M, Ekinci D, Goksu S, Supuran CT. Effects of dopaminergic compounds on carbonic anhydrase isozymes I, II, and VI. J Enzym Inhib Med Ch. 2012; 27: 365-69.
• . Ekinci D, Cavdar H, Durdagi S, Talaz O, Senturk M, Supuran CT. Structure–activity relationships for the interaction of 5,10-Dihydroindeno[1,2-b]indole derivatives with human and bovine carbonic anhydrase isoforms I, II, III, IV and VI . Eur J Med Ch. 2012; 49: 68-73.
• . Cavdar H, Ekinci D, Talaz O, Saracoglu N, Senturk M, Supuran CT. α-Carbonic anhydrases are sulfatases with cyclic diol monosulfate esters. J Enzym Inhib Med Ch. 2012; 27: 148-54.
• . Balaydin HT, Soyut H, Ekinci D, Goksu S, Beydemir S, Menzek A, Sahin E. Synthesis and carbonic anhydrase inhibitory properties of novel bromophenols including natural products. J Enzym Inhib Med Ch. 2012; 27:43-50.
• . Demirdag R, Yerlikaya E, Senturk M, Kufrevioglu OI, Ekinci D. Influence of pesticides on the pH regulatory enzyme, carbonic anhydrase, from European Seabass liver and bovine erythrocytes. Environ Toxicol Pharm. 2012; 34:218-22.
• . Ekinci D, al-Rashida M, Abbas G, Senturk M, Supuran CT. Chromone containing sulfonamides as potent carbonic anhydrase inhibitors. J Enzym Inhib Med Ch. 2012; 27:744-47.
• . Ekinci D, Kurbanoglu NI, Salamcı E, Senturk M, Supuran CT. Carbonic anhydrase inhibitors: inhibition of human and bovine isoenzymes by benzenesulfonamides, cyclitols and phenolic compounds. J Enzym Inhib Med Ch. 2012; doi: 10.3109/14756366.2011.621122
• . Ekinci D, Karagoz L, Ekinci D, Senturk M, Supuran CT. Carbonic anhydrase inhibitors: in vitro inhibition of α isoforms (hCA I, hCA II, bCA III, hCA IV) by flavonoids. J Enzym Inhib Med Ch. 2012; doi:10.3109/14756366.2011.643303
• . Ozdemir ZO, Senturk M, Ekinci D. Inhibition of mammalian carbonic anhydrase isoforms I, II and VI with thiamine and thiamine-like molecules. J Enzym Inhib Med Ch. 2012; doi:10.3109/14756366.2011.637200
• . Koz O, Ekinci D, Senturk M, Perrone A, Piacente S, Alankus-Caliskan O, Bedir E, Supuran CT. Analysis of saponins and phenolic compounds as inhibitors of α-carbonic anhydrase isoenzymes. J Enzym Inhib Med Ch. 2012; doi:10.3109/14756366.2011.651464
• . Ciftci M, Beydemir S¸ Yılmaz H, Bakan E. Effects of some drugs on rat erythrocyte 6-phosphogluconate dehydrogenase: An in vitro and in vivo study. Pol J Pharm. 2002; 54: 275-280.
• . Coban TA, Senturk M, Ciftci M, Kufrevioglu OI. Effects of some metal ions on human erythrocyte glutathione reductase: an in vitro study. Protein Peptide Lett. 2007; 14: 1027-1030.
• . Demirdag R, Yerlikaya E, Senturk M, Kufrevioglu OI, Supuran CT. Heavy metal ion inhibition studies of human, sheep and fish α-carbonic anhydrases. J Enzym Inhib Med Ch. 2012; (in press).
• . Lutz E, Lind B, Herin P et al (1996) Concentrations of mercury, cadmium, and lead in brain and kidney of second trimester foetuses and infants. J Trace Elem Med Bio 10:61–67.
• . Raspanti E, Cacciola S.O, Gotor C, Romero LC, Garcia I. Implications of cysteine metabolism in the heavy metals response in Trichoderma harzianum and in three Fusarium species. Chemosphere 2009; 76:48-54.
• . Demirdag R, Yerlikaya E, Kufrevioglu OI. Purification of carbonic anhydrase-II from sheep liver and inhibitory effects of some heavy metals on enzyme activity. J Enzym Inhib Med Ch. 2011. (doi:10.3109/14756366.2011.615744)
• . Ceyhun SB, Senturk M, Erdogan O, Kufrevioglu OI. In vitro and in vivo effects of some pesticides on carbonic anhydrase enzyme from rainbow trout (oncorhynchus mykiss) gills. Pesticide Biochem Physiol. 2010; 97: 177-181.
• . Senturk M, Kufrevioglu OI, Ciftci M. Effects of some analgesic and anestethic drugs on human erythrocyte glutathione reductase: an in vitro study. J Enzym Inhib Med Ch. 2009; 24: 420-424.
• . Coban TA, Beydemir S, Gucin I, Ekinci D, Innocenti A, Vullo D, Supuran CT. Sildenafil is a strong activator of mammalian carbonic anhydrase isoforms I-XIV. Bioorg Med Chem. 2012; 17: 5791-5795.