Protective Effect of Chitosan Against Lead-Induced Oxidative Stress in Rat Kidney

Abstract

                        Chitosan is a natural polymer with antioxidant and chelating properties. This study investigated the effects of chitosan on lead (Pb), malondialdehyde (MDA), 8-hydroxydeoxyguanosine (8-OHdG), glutathione (GSH), ceruloplasmin concentrations and catalase (CAT) activity in the kidney tissue of the rats exposed to lead. 28 male Wistar albino rats were divided into four groups of eight each: control (C), lead group (Pb group), lead+ chitosan (Pb+CS group), and chitosan (CS group). The lead group was administered 50 mg/kg lead acetate intraperitoneally (ip) for 5 days, and the chitosan groups (CS+Pb and CS groups) were administered 200 mg/kg chitosan for 28 days via gavage. At the end of the study, Pb, MDA, 8-OHdG, ceruloplasmin, GSH concentrations and catalase activity were measured in the kidney tissue. In the Pb-treated groups when compared with the control group, Pb, MDA, 8-OHdG, ceruloplasmin concentrations were significantly increased, and GSH concentration and catalase activity were significantly decreased (p<0.05). Coadministration of chitosan with lead significantly decreased Pb, MDA, and ceruloplasmin levels and significantly increased CAT activity in the kidney tissue (p<0.05). There were no significant changes in GSH and 8-OHDG levels (p>0.05). The obtained results show that chitosan protects the kidney against lead-induced oxidative stress.

Keywords

• Chitosan,Lead,Kidney,Oxidative stress

Rat Böbrek Dokusunda Kurşunun Neden Olduğu Oksidatif Strese Karşı Kitosanın Koruyucu etkisi

Abstract

Kitosan antioksidan ve şelatör özelliğe sahip doğal bir polimerdir. Bu çalışmada kurşun toksikosyonu oluşturulmuş ratların böbrek dokusu kurşun (Pb), molandialdehit (MDA), 8-hidroksi deoksiguanozin (8-OHdG), glutatyon (GSH), seroloplazmin konsantrasyonu ve katalaz aktivitesi üzerine kitosanın etkisi araştırıldı. Her grupta sekiz adet olacak şekilde 28 adet erkek Wistar albino rat, kontrol (C), kurşun grubu (Pb grubu), kurşun+kitosan (Pb+CS grubu) ve kitosan (CS grubu) olmak üzere dört gruba ayrıldı. Kurşun grubuna 5 gün, 50 mg/kg kurşun asetat intraperitonel (ip) ve kitosan gruplarına (CS+Pb ve CS grupları) 28 gün boyunca 200 mg/kg kitosan gavaj yoluyla uygulandı. Çalışma sonunda, kurşun, MDA, 8-OHdG, seruloplazmin, GSH konsantrasyonu ve katalaz aktivitesi böbrek dokusunda ölçüldü. Kontrol grubu ile karşılaştırıldığında, Pb uygulanan gruplarda böbrek dokusunda Pb, MDA, 8-OHdG ve seruloplazmin seviyesi arttı, GSH seviyesi ile katalaz aktivitesi ise azaldı (p<0.05). Kurşun ile birlikte kitosan verilmesi böbrek dokusunda Pb, MDA ve seruloplazmin seviyelerini azalttı, CAT aktivitesini arttırdı (p<0.05). GSH ve 8-OHdG seviyelerinde önemli değişiklik olmadı (p>0.05). Elde edilen sonuçlar, kitosanın, kurşun uygulaması oluşan oksidatif streseten böbreği koruduğunu göstermektedir.Her grupta sekiz adet olacak şekilde 28 adet male Wistar albino rat control (C), lead group (Pb group), lead+ chitosan (Pb+CS group) ve chitosan (CS group) olmak üzere dört gruba ayrıldı. Lead group were administered 50 mg/kg lead acetate intraperitoneal (ip) for 5 days and chitosan groups (CS+Pb and CS groups) were adminestered 200 mg/kg chitosan for 28 days via gavage. At the end the study, lead, MDA, 8-OHdG, seruloplazmin, GSH konsantrasyonu ve katalaz aktivitesi böbrek dokusunda ölçüldü.

Kontrol grubu ile karşılaştırıldığında, Pb uygulanan gruplarda böbrek dokusunda Pb, MDA, 8-OHdG ve seruloplazmin seviyesi arttı, GSH seviyesi ile katalaz aktivitesi ise azaldı (p<0.05). Kurşun ile birlikte kitosan verilmesi böbrek dokusunda Pb, MDA ve seruloplazmin seviyelerini azalttı, CAT aktivitesini arttırdı (p<0.05). GSH ve 8-OHdG seviyelerinde önemli değişiklik olmadı (p>0.05).

Elde edilen sonuçlar, kitosanın, kurşun uygulaması oluşan oksidatif streseten böbreği koruduğunu göstermektedir.

Keywords

• Kitosan,Kurşun,Böbrek,Oksidatif stres

References

1. Abdel Moneim AE, Dkhil MA, Al-Quraishy S (2011). The protective effect of flaxseed oil on lead acetate-induced renal toxicity in rats. J Hazard Mater, 194, 250-255.
2. Aykin-Burns N, Laegeler A, Kellogg G, Ercal N (2003). Oxidative effects of lead in young and adult Fisher 344 rats. Arch Environ Contam Toxicol, 44, 0417-0420.
3. Aziz F, Maulood I, Chawsheen M (2012). Effects of melatonin, vitamin Cand E alone or in combination on lead-induced injury in liver and kidney organs of rats. IOSR J Pharm, 2 (5), 13-18.
4. Bas H, Kalender Y, Pandir D, Kalender S (2015) Effects of lead nitrate and sodium selenite on DNA damage and oxidative stress in diabetic and non-diabetic rat erythrocytes and leucocytes. Environ Toxicol Pharmacol, 39, 1019-1026.
5. Beutler E, Duron O, Kelly BM (1963). Improved method for the determination of blood glutathione. J Lab Clin Med, 61, 882-888.
6. Bokara KK, Brown E, McCormick R, Yallapragada PR, Rajanna S, Bettaiya R (2008). Lead-induced increase in antioxidant enzymes and lipid peroxidation products in developing rat brain. Biometals, 21, 9-16.
7. Chien PJ, Sheu F, Huang WT, Su MS (2007). Effect of molecular weight of chitosans on their antioxidative activities in apple juice. Food chemistry, 102, 1192-1198.
8. Ercal N, Treeratphan P, Hammond TC, Matthews RH, Grannemann NH, Spitz DR (1996). In vivo indices of oxidative stress in lead-exposed C57BL/6 mice are reduced by treatment with meso-2,3-dimercaptosuccinic acid or N-acetylcysteine. Free Radic Biol Med, 21, 157-161.

9. Farmand F, Ehdaie A, Roberts, C. K., Sindhu, R. K. (2005) Lead-induced dysregulation of superoxide dismutases, catalase, glutathione peroxidase, and guanylate cyclase. Environ Res, 98, 33-39.
10. Finkel T, Holbrook NJ (2000). Oxidants, oxidative stress and the biology of ageing. Nature, 408, 239-247.
11. Flora SJ (2009). Structural, chemical and biological aspects of antioxidants for strategies against metal and metalloid exposure. Oxid Med Cell Longev, 2, 191-206.
12. Flora SJ, Bhattacharya R, Vijayaraghavan R (1995). Combined therapeutic potential of meso-2,3-dimercaptosuccinic acid and calcium disodium edetate on the mobilization and distribution of lead in experimental lead intoxication in rats. Fundam Appl Toxicol, 25, 233-240.
13. Flora SJ, Pachauri V (2010). Chelation in metal intoxication. Int J Environ Res Public Health, 7, 2745-2788.
14. Flora S, Jeevaratnam K, Kumar D (1993). Preventive effects of sodium molybdate in lead intoxication in rats. Ecotoxicol Environ Saf, 26, 133-137.
15. Galazyn-Sidorczuk M, Brzoska MM, Jurczuk M, Moniuszko-Jakoniuk J (2009). Oxidative damage to proteins and DNA in rats exposed to cadmium and/or ethanol. Chem Biol Interact, 180, 31-38.
16. Guo Z, Liu H, Chen X, Ji X, Li P (2006). Hydroxyl radicals scavenging activity of N-substituted chitosan and quaternized chitosan. Bioorg Med Chem Lett, 16, 6348-6350.
17. Guo Z, Xing R, Liu S, Yu H, Wang P, Li C, Li P (2005). The synthesis and antioxidant activity of the Schiff bases of chitosan and carboxymethyl chitosan. Bioorg Med Chem Lett, 15, 4600-4603.
18. Guo Z, Xing R, Liu S, Zhong Z, Li P (2008). Synthesis and hydroxyl radicals scavenging activity of quaternized carboxymethyl chitosan. Carbohydr Polym, 73, 173-177.
19. Halliwell B, Gutteridge JM, Cross CE (1992). Free radicals, antioxidants, and human disease: where are we now? J Lab Clin Med, 119, 598-62.
20. Han S, Qiao X, Simpson S, Ameri P, Kemp FW, Bogden JD (1996). Weight loss alters organ concentrations and contents of lead and some essential divalent metals in rats previously exposed to lead. J Nutr, 126, 317-323.
21. Hsu PC, Guo YL (2002). Antioxidant nutrients and lead toxicity. Toxicology, 180, 33-44.Iqbal M, Okazaki Y, Okada S (2009). Curcumin attenuates oxidative damage in animals treated with a renal carcinogen, ferric nitrilotriacetate (Fe-NTA): implications for cancer prevention. Mol Cell Biochem, 324, 157-164.
22. Je JY, Kim SK (2006). Reactive oxygen species scavenging activity of aminoderivatized chitosan with different degree of deacetylation. Bioorg Med Chem, 14, 5989-5994.
23. Jeon TI, Hwang SG, Park NG, Jung YR, Im Shin S, Choi SD, Park DK (2003). Antioxidative effect of chitosan on chronic carbon tetrachloride induced hepatic injury in rats. Toxicology, 187, 67-73.
24. Jin X, Chan HM, Lok E et al. (2008). Dietary fats modulate methylmercury-mediated systemic oxidative stress and oxidative DNA damage in rats. Food Chem Toxicol, 46, 1706-1720.
25. Jurczuk M, Moniuszko-Jakoniuk J, Brzoska MM (2006). Involvement of some low-molecular thiols in the peroxidative mechanisms of lead and ethanol action on rat liver and kidney. Toxicology, 219, 11-21.
26. Kim KW, Thomas R (2007). Antioxidative activity of chitosans with varying molecular weights. Food chemistry, 101, 308-313.
27. Lakshmi BV, Sudhakar M, Aparna M (2013). Protective potential of Black grapes against lead induced oxidative stress in rats. Environ Toxicol Pharmacol, 35, 361-368.
28. Lartillot S, Kedziora P, Athias A (1988). Purification and characterization of a new fungal catalase. Prep Biochem, 18, 241-246.
29. Ledwozyw A, Michalak J, Stepien A, Kadziolka A (1986). The relationship between plasma triglycerides, cholesterol, total lipids and lipid peroxidation products during human atherosclerosis. Clinica chimica acta,155, 275-283.
30. Lee MJ, Jung CH, Kang YM et al. (2015). Serum Ceruloplasmin Level as a Predictor for the Progression of Diabetic Nephropathy in Korean Men with Type 2 Diabetes Mellitus. Diabetes Metab J, 39, 230-239.
31. Li Z, Piao F, Liu S, Wang Y, Qu S (2010). Subchronic exposure to arsenic trioxide-induced oxidative DNA damage in kidney tissue of mice. Exp Toxicol Pathol, 62, 543-547.
32. Liu CM, Ma JQ, Sun YZ (2010). Quercetin protects the rat kidney against oxidative stress-mediated DNA damage and apoptosis induced by lead. Environ Toxicol Pharmacol, 30, 264-271.
33. Liu CM, Zheng YL, Lu J et al. (2010). Quercetin protects rat liver against lead-induced oxidative stress and apoptosis. Environ Toxicol Pharmacol. 29, 158-166.
34. Liu J, Sun H, Dong F et al. (2009). The influence of the cation of quaternized chitosans on antioxidant activity. Carbohydr Polym, 78, 439-443.
35. Matos RC, Vieira C, Morais S, de Lourdes Pereira M, de Jesus JP (2009). Nephrotoxicity of CCA-treated wood: A comparative study with As(2)O(5) and CrO(3) on mice. Environ Toxicol Pharmacol. 27, 259-263.
36. Matovic V, Buha A, Ethukic-Cosic D, Bulat Z (2015). Insight into the oxidative stress induced by lead and/or cadmium in blood, liver and kidneys. Food Chem Toxicol, 78, 130-140.
37. Mongiat R, Gerli GC, Locatelli GF, Fortuna R, Petazzi A (1992). Erythrocyte antioxidant system and serum ceruloplasmin levels in welders. Int J Occup Environ Health, 64, 339-342.
38. Mutlu N, Ersan Y, Nur G, Koç E (2011). Protective effect of caffeic acid phenethyl ester against lead acetate-induced hepatotoxicity in mice. Kafkas Univ Vet Fak Derg, 17, 1-5.
39. Onsoyen E, Skaugrud O (1990). Metal recovery using chitosan. J Chem Technol Biotechnol, 49, 395-404.
40. Pande M, Flora SJ (2002). Lead induced oxidative damage and its response to combined administration of alpha-lipoic acid and succimers in rats. Toxicology, 177, 187-196.
41. Park PJ, Je JY, Kim SK (2004). Free radical scavenging activities of differently deacetylated chitosans using an ESR spectrometer. Carbohydr Polym, 55, 17-22.
42. Patrick L (2006). Lead toxicity, a review of the literature. Part 1: Exposure, evaluation, and treatment. Altern Med Rev, 11, 2-22.
43. Reyes H, Baez ME, Gonzalez MC et al. (2000). Selenium, zinc and copper plasma levels in intrahepatic cholestasis of pregnancy, in normal pregnancies and in healthy individuals, in Chile. J Hepatol, 32, 542-549.
44. Saxena G, Flora SJ (2004). Lead-induced oxidative stress and hematological alterations and their response to combined administration of calcium disodium EDTA with a thiol chelator in rats. J Biochem Mol Toxicol, 18, 221-233.
45. Sharma S, Singh B (2014). Effects of acute and chronic lead exposure on kidney lipid peroxidation and antioxidant enzyme activities in BALB-C mice (Mus musculus). Int J Sci Res, 3, 1564-1566.
46. Sharma V, Sharma A, Kansal L (2010). The effect of oral administration of Allium sativum extracts on lead nitrate induced toxicity in male mice. Food Chem Toxicol, 48, 928-936.
47. Shukla N, Maher J, Masters J, Angelini GD, Jeremy JY (2006). Does oxidative stress change ceruloplasmin from a protective to a vasculopathic factor? Atherosclerosis, 187, 238-250.
48. Sivaprasad R, Nagaraj M, Varalakshmi P (2004). Combined efficacies of lipoic acid and 2,3-dimercaptosuccinic acid against lead-induced lipid peroxidation in rat liver. J Nutr Biochem, 15, 18-23.
49. Sun T, Xie W, Xu P (2004). Superoxide anion scavenging activity of graft chitosan derivatives. Carbohydr Polym, 58, 379-382.
50. Sun T, Yao Q, Zhou D, Mao F (2008). Antioxidant activity of N-carboxymethyl chitosan oligosaccharides. Bioorg Med Chem Lett, 18, 5774-5776.
51. Sunderman, FWJr, Nomoto S (1970). Measurement of human serum ceruloplasmin by its p-phenylenediamine oxidase activity. Clin chem, 16, 903-910.
52. Tokar EJ, Diwan BA, Waalkes MP (2010). Early life inorganic lead exposure induces testicular teratoma and renal and urinary bladder preneoplasia in adult metallothionein-knockout mice but not in wild type mice. Toxicology 276, 5-10
53. Toz H, Deger Y (2017). The Effect of Chitosan on the Erythrocyte Antioxidant Potential of Lead Toxicity-Induced Rats. Biol Trace Elem Res, 184 (1), 114-118.
54. Wang J, Yang Z, Lin L, Zhao Z, Liu Z, Liu X (2012). Protective effect of naringenin against lead-induced oxidative stress in rats. Biol Trace Elem Res, 146, 354-359.
55. Wang Z. Yan Y, Yu X, Li W, Li B, Qin C (2016). Protective effects of chitosan and its water-soluble derivatives against lead-induced oxidative stress in mice. Int J Biol Macromol, 83, 442-449.
56. Xie W, Xu P, Liu Q (2001). Antioxidant activity of water-soluble chitosan derivatives. Bioorg. Med. Chem. Lett, 11, 1699-1701.
57. Xing R, Yu H, Liu S, et al. (2005). Antioxidant activity of differently regioselective chitosan sulfates in vitro. Bioorg Med Chem, 13, 1387-1392.
58. Yahaya MI, Ogunfowokan AO, Orji EO (2011). Elemental profile in amniotic fluid of some Nigerian pregnant women. East Afr J Public Health, 8, 92-97.
59. Yang S, Guo Z, Miao F, Xue Q, Qin S (2010). The hydroxyl radical scavenging activity of chitosan, hyaluronan, starch and their O-carboxymethylated derivatives. Carbohydr Polym, 82, 1043-1045.