题名

Antioxidant Effects of Melatonin and Coenzyme Q10 on Oxidative Damage Caused by Single-Dose Ochratoxin A in Rat Kidney

DOI

10.4077/CJP.2010.AMK073

作者

Aydin Yenilmez;Burhanettin Isikli;Erinc Aral;Irfan Degirmenci;Emine Sutken;Cengiz Baycu

关键词

coenzyme Q10 ; melatonin ; mitotic index ; ochratoxin A ; oxidative stress

期刊名称

The Chinese Journal of Physiology

卷期/出版年月

53卷5期(2010 / 10 / 31)

页次

310 - 317

内容语文

英文

英文摘要

In the study, the effects of relatively high single-dose of Ochratoxin A (OTA) and the antioxidant effects of Melatonin (Mel) and Coenzyme Q10 (CoQ10) on OTA-induced oxidative damages in rats were investigated. A total of 28 male Sprague-Dawley rats were divided into four groups of 7 rats each: Control, OTA, Mel+OTA and CoQ10+OTA groups. Malondialdehyde (MDA) levels in the plasma and glutathione (GSH) levels in whole blood were measured; kidneys (for histological inspection and for apoptosis detection by TUNEL method) and bone marrow samples (for chromosome aberration and mitotic index) were taken. The rats in the OTA group showed limited degeneration of tubular cells. In some tubules karyomegaly, desquamated cells and vacuolization were observed by light microscopy. Mel and CoQ10 treatment significantly reduced the severity of the lesions. MDA levels of the OTA group were significantly higher than the control, OTA+Mel and OTA+CoQ10 groups, while GSH levels were significantly lower than the control, OTA+Mel and OTA+CoQ10 groups. Higher incidences of apoptotic bodies were observed in the kidneys of the OTA group although OTA administration did not significantly change the incidence of apoptotic bodies when compared to the control and antioxidant administrated groups. Although the percentage of the mitotic index was lowest in the OTA group, no statistical difference was found among the groups. Additionally, OTA had no numerical and structural significant effects on chromosomes. It was observed that single-dose OTA administration caused oxidative damages in rat kidney and Mel or CoQ10 treatment appeared to ameliorate the OTA-induced tissue injuries.

主题分类 醫藥衛生 > 基礎醫學
参考文献
  1. Abdel-Wahhab, M. A.,Abdel-Galil, M. M.,El-Lithey, M.(2005).Melatonin counteracts oxidative stress in rats fed an ochratoxin A contaminated diet.J. Pineal Res.,38,130-135.
  2. Albassam, M. A.,Yong, S. I.,Bhatnagar, R.,Sharma, A. K.,Prior, M. G.(1987).Histopathologic and electron microscopic studies on the acute toxicity of ochratoxin A in rats.Vet. Pathol.,24,427-435.
  3. Atroshi, F.,Biese, I.,Saloniemi, H.,Ali-Vehmas, T.,Saari, S.,Rizzo, A.,Veijalainen, P.(2000).Significance of apoptosis and its relationship to antioxidants after ochratoxin A administration in mice.J. Pharm. Pharm. Sci.,3,281-291.
  4. Aydin, G.,Ozcelik, N.,Cicek, E.,Soyoz, M.(2003).Histopathologic changes in liver and renal tissues induced by Ochratoxin A and melatonin in rats.Hum. Exp. Toxicol.,22,383-391.
  5. Beutler, E.(1957).The glutathione instability of drug-sensitive red cells: a new method for the in vitro detection of drug sensitivity.J. Lab. Clin. Med.,49,84-95.
  6. Boorman, G. A.,McDonald, M. R.,Imoto, S.,Persing, R.(1992).Renal lesions induced by ochratoxin A exposure in the F344 rat.Toxicol. Pathol.,20,236-245.
  7. Dirheimer, G.,Creppy, E. E.(1991).Mechanism of action of ochratoxin A.IARC. Sci. Publ.,115,171-186.
  8. Gautier, J. C.,Holzhaeuser, D.,Markovic, J.,Gremaud, E.,Schilter, B.,Turesky, R. J.(2001).Oxidative damage and stress response from ochratoxin A exposure in rats.Free Radic. Biol. Med.,30,1089-1098.
  9. Gekle, M.,Schwerdt, G.,Freudinger, R.,Mildenberger, S.,Wilflingseder, D.,Pollack, V.,Dander, M.,Schramek, H.(2000).Ochratoxin A induces JNK activation and apoptosis in MDCK-C7 cells at nanomolar concentrations.J. Pharmacol. Exp. Ther.,293,837-844.
  10. Gekle, M.,Silbernagl, S.(1994).The role of the proximal tubule in ochratoxin A nephrotoxicity in vivo: toxodynamic and toxokinetic aspects.Ren. Physiol. Biochem.,17,40-49.
  11. Gekle, M.,Silbernagl, S.(1996).Renal toxicodynamics of ochratoxin A: a pathophysiological approach.Kidney Blood Press. Res.,19,225-235.
  12. Kamp, H. G.,Eisenbrand, G.,Janzowski, C.,Kiossev, J.,Latendresse, J. R.,Schlatter, J.,Turesky, R. J.(2005).Ochratoxin A induces oxidative DNA damage in liver and kidney after oral dosing to rats.Mol. Nutr. Food Res.,49,1160-1167.
  13. Kanisawa, M.,Suzuki, S.,Kozuka, Y.,Yamazaki, M.(1977).Histopathological studies on the toxicity of ochratoxin A in rats.I. Acute oral toxicity. Toxicol. Appl. Pharmacol.,42,55-64.
  14. Krogh, P.(1978).Causal association of mycotoxic nephropathy.Acta Pathol. Microbiol. Scand. Suppl.,269,1-28.
  15. Kuiper-Goodman, T.,Scott, P. M.(1989).Risk assessment of the mycotoxin ochratoxin A.Biomed. Environ. Sci.,2,179-248.
  16. Li, S.,Marquardt, R. R.,Frohlich, A. A.(2000).Identification of ochratoxins and some of their metabolites in bile and urine of rats.Food Chem. Toxicol.,38,141-152.
  17. Linnane, A. W.,Marzuki, S.,Ozawa, T.,Tanaka, M.(1989).Mitochondrial DNA mutations as an important contributor to ageing and degenerative diseases.Lancet,1(8639),642-645.
  18. Lioi, M. B.,Santoro, A.,Barbieri, R.,Salzano, S.,Ursini, M. V.(2004).Ochratoxin A and zearalenone: a comperative study on genotoxic effects and cell death induced in bovine lymphoytes.Mutat. Res.,557,19-27.
  19. Manolova, Y.,Manolov, G.,Parvanova, L.,Petkova-Bocharova, T.,Castegnaro, M.,Chernozemsky, I. N.(1990).Induction of characteristic chromosomal aberrations, particularly X-trisomy, in cultured human lymphocytes treated by ochratoxin A, a myotoxin implicated in Balkan endemic nephropathy.Mutat. Res.,231,143-149.
  20. Meki, A. R.,Hussein, A. A.(2001).Melatonin reduces oxidative stress induced by ochratoxin A in rat liver and kidney.Comp. Biochem. Physiol. C. Toxicol. Pharmacol.,130,305-313.
  21. Obrecht-Pflumio, S.,Dirheimer, G.(2000).In vitro DNA and dGMP adducts formation caused by ochratoxin A.Chem. Biol. Interact.,127,29-44.
  22. Ohkawa, H.,Ohishi, N.,Yagi, K.(1979).Assay for lipid peroxides in animal tissues by thiobarbituric acid reaction.Anal. Biochem.,95,351-358.
  23. Ozcelik, N.,Soyoz, M.,Kilinc, I.(2004).Effects of ochratoxin A on oxidative damage in rat kidney: protective role of melatonin.J. Appl. Toxicol.,24,211-215.
  24. Petrik, J.,Zanic-Grubisic, T.,Barisic, K.,Pepeljnjak, S.,Radic, B.,Ferencic, Z.,Cephelac I.(2003).Apoptosis and oxidative stress induced by ochratoxin A in rat kidney.Arch. Toxicol.,77,685-693.
  25. Pfohl-Leszkowicz, A.,Chakor, K.,Creppy, E. E.,Dirheimer, G.(1991).DNA adduct formation in mice treated with ochratoxin A.IARC Sci. Publ.,115,245-253.
  26. Pieri, C.,Marra, M.,Moroni, F.,Recchioni, R.,Marcheselli, F.(1994).Melatonin: a peroxyl radical scavenger more effective than vitamin E.Life Sci.,55,PL271-PL276.
  27. Poeggeler, B.,Reiter, R. J.,Tan, D. X.,Chen, L. D.,Manchester, L. C.(1993).Melatonin, hydroxyl radical-mediated oxidative damage, and aging: a hypothesis.J. Pineal Res.,14,151-168.
  28. Quiles, J. L.,Ochoa, J. J.,Huertas, J. R.,Mataix, J.(2004).Coenzym Q supplementation protects from age-related DNA double-strand breaks and increases lifespan in rats fed on a PUFA-rich diet.Exp. Gerontol.,39,189-194.
  29. Rahimtula, A. D.,Bereziat, J. C.,Bussacchini-Griot, V.,Bartsch, H.(1988).Lipid peroxidation as a possible cause of ochratoxin A toxicity.Biochem. Pharmacol.,37,4469-4477.
  30. Reiter, R. J.(1996).Antioxidant actions of melatonin.Adv. Pharmacol.,38,103-117.
  31. Reiter, R. J.,Melchiorri, D.,Sewerynek, E.,Poeggeler B.,Barlow-Walden, L.,Chuang, J.,Ortiz, G. G.,Acuna-Castroviejo, D.(1995).A review of the evidence supporting melatonin's role as an antioxidant.J. Pineal Res.,18,1-11.
  32. Robbiano, L.,Baroni, D.,Carrozzino, R.,Mereto, E.,Brambilla, G.(2004).DNA damage and micronuclei induced in rat and human kidney cells by six chemicals carcinogenic to the rat kidney.Toxicology,204,187-195.
  33. Schaaf, G. J.,Nijmeijer, S. M,Maas, R. F.,Roestenberg, P.,de Groene, E. M.,Fink-Gremmels, J.(2002).The role of oxidative stress in the ochratoxin A-mediated toxicity in proximal tubular cells.Biochim. Biophys. Acta,1588,149-158.
  34. Schwerdt, G.,Freudinger, R.,Mildenberger, S.,Silbernagl, S.,Gekle, M.(1999).The nephrotoxin ochratoxin A induces apoptosis in cultured human proximal tubule cells.Cell. Biol. Toxicol.,15,405-415.
  35. Seegers, J. C.,Bohmer, L. H.,Kruger, M. C.,Lottering, M. L.,de Kock, M.(1994).A comparative study of ochratoxin A-induced apoptosis in hamster kidney and HeLa cells.Toxicol. Appl. Pharmacol.,129,1-11.
  36. Sutken, E.,Aral, A.,Ozdemir, F.,Uslu, S.,Alatas, O.,Colak, O.(2007).Protective role of melatonin and coenzyme Q10 in ochratoxin A toxicity in rat liver and kidney.Int. J. Toxicol.,26,81-87.
被引用次数
  1. Zivkovic, Vladimir,Vuletic, Milena,Stojimirovic, Biljana,Pesic, Snezana,Milinkovic, Marija,Jakovljevic, Vladimir,Djuric, Dragan,Barudzic, Nevena(2015).Assessment of Oxidative Status in Patients with Acute Kidney Injury: A Pilot Study.中國生理學雜誌,58(2),124-133.