Protective Effect of Quercetin Against Renal Toxicity Induced by Cadmium in Rats

Year 2012, , 56 - 61, 01.01.2012

Tevfik Aktoz Mehmet Kanter Yeşim Hülya Uz Cevat Aktaş Mustafa Erboğa İrfan Hüseyin Atakan

https://doi.org/10.5152/balkanmedj.2011.014

Abstract

Objective: The aim of the present study was to examine the protective effect of quercetine (QE) against cadmium (Cd)-induced renal toxicity. Material and Methods: A total of 24 male Wistar albino rats were divided into three groups: control, Cd-treated and Cd-treated with QE; each group containing 8 animals. The Cd-treated group was injected subcutaneously with CdCl2 dissolved in saline in the dose of 2 ml/kg/day for 30 days, resulting in a dosage of 1 mg/kg Cd. The rats in the QE treated groups were given QE (15 mg/kg body weight) once a day intraperitoneally starting 2 days prior to Cd injection during the study period. Results: The renal histology in Cd-treated rats showed mesangial expansion, thickening of capsular basement membranes, glomerular basement membranes and tubular basement membranes, characterized by an increase in periodic acid Schiff (PAS)-positive areas as compared with control animals. With the QE treatment, despite the presence of only a few swollen glomeruli, we noticed a marked protection of renal structure when compared with the Cd-treated rats. Furthermore, QE pretreatment resulted in increased proliferating cell nuclear antigen (PCNA) immunoreactivity and decreased the activity of Terminal Transferase dUTP Nick End Labeling (TUNEL). Conclusion: These findings suggest that QE may attenuate Cd-induced renal toxicity. Turkish Başlık: Sıçanlarda Kadmiyumla Oluşturulan Böbrek Toksisitesine Karşı Quercetinin Koruyucu Etkisi Anahtar Kelimeler: Böbrek toksitesi, immünohistokimya, kadmiyum, quercetin, TUNEL Amaç: Çalışmamızda kadmiyumla (Cd) oluşturulan böbrek toksisitesine karşı quercetinin (QE) koruyucu etkinliğini göstermeyi amaçladık. Hastalar ve Yöntemler: Çalışmada 24 adet Wistar albino cinsi erişkin erkek sıçan kullanıldı. Sıçanlar her grupta 8 adet olmak üzere; kontrol, Cd ve Cd+QE olmak üzere 3 gruba ayrıldı. Cd grubuna her gün 1 mg/kg Cd, 2 ml/kg serum fizyolojik içerisinde çözündürüldükten sonra CdCl2 şeklinde 30 gün boyunca subkutan enjeksiyon olarak uygulandı. Cd ile birlikte QE tedavisi verilen gruba, Cd enjeksiyonundan 2 gün önce başlanarak 15 mg/kg QE, deney süresi boyunca intraperitoneal olarak uygulandı. Bulgular: Böbrek dokularının histolojik olarak değerlendirilmesi sonucu, kontrol grubuyla karşılaştırıldığında Cd verilen sıçanlarda mezengial hücrelerde artış, kapsüler, glomerüler ve tübüler basal membranlarda kalınlaşma ile birlikte periyodik asit Schiff (PAS)-pozitif alanların artışı gözlendi. Cd ile birlikte QE tedavisi verilen grupta sadece birkaç glomerüldeki genişleme dışında, Cd'ye bağlı böbrek yapısında oluşan değişikliklere karşı QE'nin belirgin koruyucu bir etkisinin olduğu saptandı. Bulgularımız, Cd ile birlikte QE tedavisi verilen grupta böbrek kortikal dokularında TdT-(terminal deoksinukleotidil transferaz)- aracılı deoksiuridin trifosfat işaretleme (TUNEL) aktivitesinde anlamlı bir azalma ile birlikte prolifere olmuş hücre nükleer antijeninin (PCNA) ekspresyonunda da artış olduğunu göstermiştir. Sonuç: Bu sonuçlar QE'nin Cd ile oluşturulan böbrek toksisitesini azaltabileceğini göstermiştir.

Keywords

Cadmium, immunohistochemistry, quercetin, renal toxicity, TUNEL

Protective Effect of Quercetin Against Renal Toxicity Induced by Cadmium in Rats

Abstract

References

• Waisberg M, Joseph P, Hale B, Beyersmann D. Molecular and cellular mechanisms of cadmium carcinogenesis. Toxicology 2003;192:95-117. [CrossRef]
• Koçak M, Akçil E. The effects of chronic cadmium toxicity on the hemostatic system. Pathophysiol Haemost Thromb 2006;35:411-6. [CrossRef]
• Kim SC, Cho MK, Kim SG. Cadmium-induced nonapoptotic cell death mediated by oxidative stress under the condition of sulfhy- dryl deficiency. Toxicol Lett 2003;144:325-36. [CrossRef]
• Ohta H, Yamauchi Y, Nakakita M, Tanaka H, Asami S, Seki Y, et al. Relationship between renal dysfunction and bone metabolism disorder in male rats after long-term oral quantitative cadmium administration. Industr Health 2000;38:339-55. [CrossRef]
• Washington B, Williams S, Armstrong P, Mtshali C, Robinson JT, Myles EL. Cadmium toxicity on arteriols vascular smooth muscle cells of spontaneously hypertensive rats. Int J Environ Res Public Health 2006;3:232-8. [CrossRef]
• Bernard A, Lauwerys R. Effects of cadmium exposure in humans. In Handbook of Experimental Pharmacology (E. C. Foulkes, Ed.), Springer-Verlag, Heidelberg 1986;135-77.
• Middleton E Jr. Effect of plant flavonoids on immune and inflamma- tory cell function. Adv Exp Med Biol 1998;439:175-82. [CrossRef]
• Inal ME, Akgun A, Kahraman A. Radioprotective effects of ex- ogenous glutathione against whole-body gamma-ray irradiation: age- and gender-related changes in malondialdehyde levels, su- peroxide dismutase and catalase activities in rat liver. Methods Find Exp Clin Pharmacol 2002;24:209-12. [CrossRef]
• Laughton MJ, Evans PJ, Moroney MA, Hoult JR, Halliwell B. In- hibition of mammalian 5-lipoxygenase and cyclo-oxygenase by flavonoids and phenolic dietary additives. Relationship to antioxi- dant activity and to iron ion-reducing ability. Biochem Pharmacol 1991;42:1673-81. [CrossRef]
• Afanas’ev IB, Dorozhko I, Brodskii AV, Korstyuk VA, Potapovitch A. Chelating and free radical scavenging mechanisms of inhibi- tory action of rutin and quercetin in lipid peroxidation. Biochem Pharmacol 1989;38:1763-9. [CrossRef]
• Scott R, Aughey E, Sinclair J. Histological and ultrastructural changes in rat kidney following cadmium injection. Urol Res 1977;5:15-20. [CrossRef]
• Hsu SM, Raine L, Fanger H. Use of avidinbiotin-peroxidase com- plex (ABC) in immunperoxidase techniques: a comparison be- tween ABC and unlabeled antibody (PAP) procedures. J Histo- chem Cytochem 1981;29:577-80. [CrossRef]
• Yiin SJ, Chern CL, Sheu JY, Lin TH. Cadmium-induced lipid per- oxidation in rat testes and protection by selenium. Biometals 1999;12:353-9. [CrossRef]
• Yiin SJ, Chern CL, Sheu JY, Tseng WC, Lin TH. Cadmium-induced renal lipid peroxidation in rats and protection by selenium. J Toxi- col Environ Health 1999;57:403-13. [CrossRef]
• Ohta H, Cherian MG. Gastrointestinal absorption of cadmium and metallothionein. Toxicol Appl Pharmacol 1991;107:63-72. [CrossRef]
• Nigam D, Shukla GS, Agarwal AK. Glutathione depletion and oxi- dative damage in mitochondria following exposure to cadmium in rat liver and kidney. Toxicol Lett 1999;106:151-7. [CrossRef]
• Newairy AA, El-Sharaky AS, Badreldeen MM, Eweda SM, She- weita SA. The hepatoprotective effects of selenium against cad- mium toxicity in rats. Toxicology 2007;242:23-30. [CrossRef]
• Asar M, Kayisli UA, Izgut-Uysal VN, Akkoyunlu G. Immunohisto- chemical and ultrastructural changes in the renal cortex of cadmi- um-treated rats. Biol Trace Elem Res 2004;97:249-63. [CrossRef]
• Takaki A, Jimi S, Segawa M, Hisano S, Takebayashi S, Iwasa- ki H. Longterm cadmium exposure accelerates age-related mitochondrial changes in renal epithelial cells. Toxicology 2004;203:145-54. [CrossRef]
• Griffin JL, Walker LA, Shore R, Nicholson JK. Metabolic profil- ing of chronic cadmium exposure in the rat. Chem Res Toxicol 2001;14:1428-34. [CrossRef]
• Gatta A, Bazzerla G, Amodio P, Menon F, Angeli P, Schiaffino E, et al. Detection of the early steps of cadmium nephropathy- comparison of light- and electron-microscopical patterns with the urinary enzymes excretion. An experimental study. Nephron 1989;51:20-4. [CrossRef]
• Goyer RA, Miller CR, Zhu S, Victery W. Non-metallothionein- bound cadmium in the pathogenesis of cadmium nephrotoxicity in the rat. Toxicol Appl Pharmacol 1989;101:232-44. [CrossRef]
• Shibutani M, Mitsumori K, Niho N, Satoh S, Hiratsuka H, Satoh M, et al. Assessment of renal toxicity by analysis of regeneration of tubular epithelium in rats given low-dose cadmium chloride or cadmium- polluted rice for 22 months. Arch Toxicol 2000;74:571-7. [CrossRef]
• Brzoska MM, Kaminski M, Supernak-Bobko D, Zwierz K, Moni- uszko-Jakoniuk J. Changes in the structure and function of the kidney of rats chronically exposed to cadmium. I. Biochemical and histopathological studies. Arch Toxicol 2003;77:344-52.
• Aoyagi T, Hayakawa K, Miyaji K, Ishikawa H, Hata M. Cadmium nephrotoxicity and evacuation from the body in a rat modeled subchronic intoxication. Int J Urol 2003;10:332-8. [CrossRef]
• Tanimoto A, Hamada T, Koide O. Cell death and regeneration of renal proximal tubular cells in rats with subchronic cadmium intoxication. Toxicol Pathol 1993;21:341-52. [CrossRef]
• Jacquillet G, Barbier O, Cougnon M, Tauc M, Namorado MC, Martin D, et al. Zinc protects renal function during cadmium intoxication in the rat. Am J Physiol Renal Physiol 2006;290:F127-37. [CrossRef]
• Prozialeck WC, Vaidya VS, Liu J, Waalkes MP, Edwards JR, Lamar PC, et al. Kidney injury molecule-1 (Kim-1) as an early biomarker of cadmium nephrotoxicity. Kidney Int 2007;72:985-93. [CrossRef]
• Iwai S, Matsuno K. An ultrastructual study on cadmium-induced damage of the renal proximal tubules of rats. J Med Soc Toho 1991;137:757-71.
• Walker NI, Harmon BV, Gobé GC, Kerr JF. Patterns of cell death. Meth Archiev Exp Pathol 1988;13:18-54.
• Prozialeck WC, Niewcnhuis RJ. Cadmium (Cd2+) disrupts inter- cellularjunctions and actin filaments in LLC-PKI cells. Toxicol Appl Pliarmacol 1991;107:81-97. [CrossRef]