Hostname: page-component-cd9895bd7-hc48f Total loading time: 0 Render date: 2024-12-27T14:31:23.242Z Has data issue: false hasContentIssue false
  • English
  • Français

Histochemistry evaluation of the oxidative stress and the antioxidant status in Cu-supplemented cattle

Published online by Cambridge University Press:  09 March 2012

M. García-Vaquero ,
J. L. Benedito ,
M. López-Alonso  and
M. Miranda
M. García-Vaquero*
Affiliation:
Departamento de Patoloxía Animal, Facultade de Veterinaria, Universidade de Santiago de Compostela, 27002 Lugo, Spain
J. L. Benedito
Affiliation:
Departamento de Patoloxía Animal, Facultade de Veterinaria, Universidade de Santiago de Compostela, 27002 Lugo, Spain
M. López-Alonso
Affiliation:
Departamento de Patoloxía Animal, Facultade de Veterinaria, Universidade de Santiago de Compostela, 27002 Lugo, Spain
M. Miranda
Affiliation:
Departamento de Ciencias Clínicas Veterinarias, Facultade de Veterinaria, Universidade de Santiago de Compostela, 27002 Lugo, Spain
*
†E-mail: garcia.vaquero@usc.es
Get access

Abstract

The aim of this paper is to evaluate at a histopathological level the effect of the most commonly used copper (Cu) supplementation (15 mg/kg dry matter (DM)) in the liver of intensively reared beef cattle. This was done by a histochemistry evaluation of (i) the antioxidant capacity in the liver – by the determination of metallothioneins (MT) and superoxide dismutase (SOD) expression – as well as (ii) the possible induction of oxidative damage – by the determination of inducible nitric oxide synthase (iNOS), nitrotyrosine (NITT), malondialdehyde (MDA) and 8-oxoguanine (8-oxo) – that (iii) could increase apoptotic cell death – determined by cytochrome-c (cyto-c), caspase 1 (casp1) and terminal deoxynucleotidyl transferase dUTP nick end labeling (TUNEL). Liver samples from Cu-supplemented (15 mg Cu sulphate/kg DM, n = 5) and non-supplemented calves (n = 5) that form part of other experiments to evaluate Cu status were collected at slaughter and processed for immunohistochemistry and TUNEL. MT expression was diffuse and SOD showed slight changes although without statistical significance. iNOS and NITT positive (+) cells significantly increased, mainly around the central veins in the animals from the Cu-supplemented group, whereas no differences were appreciated for the rest of the oxidative stress and apoptosis markers. Under the conditions of this study, which are the conditions of the cattle raised in intensive systems in NW Spain and also many European countries, routinely Cu supplementation increased the risk of the animals to undergo subclinical Cu toxicity, with no significant changes in the Cu storage capacity and the antioxidant defensive system evaluated by MT and SOD expression, but with a significant and important increase of oxidative damage measured by iNOS and NITT. The results of this study indicated that iNOS and NITT could be used as early markers of initial pathological changes in the liver caused by Cu supplementation in cattle, although more studies in cattle under different levels of Cu supplementation are needed.

Keywords

cattlecoppersubclinical toxicityoxidative stressantioxidant defense
Type
Full Paper
Information
animal , Volume 6 , Issue 9 , September 2012 , pp. 1435 - 1443
Copyright
Copyright © The Animal Consortium 2012

Access options

Get access to the full version of this content by using one of the access options below. (Log in options will check for institutional or personal access. Content may require purchase if you do not have access.)

References

Abd Ellah, MR, Okada, K, Goryo, M, Oishi, A, Yasuda, J 2009. Superoxide dismutase activity as a measure of hepatic oxidative stress in cattle following ethionine administration. The Veterinary Journal 182, 336–341.CrossRefGoogle ScholarPubMed
Alexandrova, A, Kebis, A, Mislanova, C, Kukan, M 2007. Copper impairs biliary epithelial cells and induces protein oxidation and oxidative DNA damage in the isolated perfused rat liver. Experimental and Toxicologic Pathology 58, 255–261.Google Scholar
Alexandrova, A, Petrov, L, Georgieva, A, Kessiova, M, Tzvetanova, E, Kirkova, M, Kukan, M 2008. Effect of copper intoxication on rat liver proteasome activity: relationship with oxidative stress. Journal of Biochemical and Molecular Toxicology 22, 354–362.CrossRefGoogle ScholarPubMed
Banasik, A, Lankoff, A, Piskulak, A, Adamowska, K, Lisowska, H, Wojcik, A 2005. Aluminum-induced micronuclei and apoptosis in human peripheral-blood lymphocytes treated during different phases of the cell cycle. Environmental Toxicology 20, 402–406.CrossRefGoogle ScholarPubMed
Bidewell, CA, David, GP, Livesey, CT 2000. Copper toxicity in cattle. Veterinary Record 147, 399–400.Google Scholar
Bremner, I, Beattie, JH 1990. Metallothionein and trace minerals. Annual Review of Nutrition 10, 63–83.CrossRefGoogle ScholarPubMed
Bremner, I, Beattie, JH 1995. Copper and zinc metabolism in health and disease: speciation and interactions. The Proceedings of the Nutrition Society 54, 489–499.CrossRefGoogle ScholarPubMed
Britton, RS 1996. Metal-induced hepatotoxicity. Seminar in Liver Diseases 16, 3–12.Google Scholar
Cerone, SI, Sansinanea, AS, Streitenberg, SA, García, MC, Auza, NJ 2000. Cytochrome c-oxidase, Cu,Zn-superoxide dismutase and caeruloplasmin activities in copper-deficient bovines. Biological Trace Element Research 73, 269–278.CrossRefGoogle ScholarPubMed
Commission Regulation 1334/2003/EC on amending the conditions for authorisation of a number of additives in feedingstuffs belonging to the group of trace elements. Official Journal of the European Union 187, 11–15.Google Scholar
Druzhyna, NM, Musiyenko, SI, Wilson, GL, LeDoux, SP 2005. Cytokines induce nitric oxide-mediated mtDNA damage and apoptosis in oligodendrocytes. Protective role of targeting 8-oxoguanine glycosylase to mitochondria. Journal of Chemical Biology 280, 21673–21679.CrossRefGoogle ScholarPubMed
Formigari, A, Irato, P, Santon, A 2007. Zinc, antioxidant systems and metallothionein in metal mediated-apoptosis: biochemical and cytochemical aspects. Comparative biochemistry and physiology. Toxicology & Pharmacology 146, 443–459.Google Scholar
Gaetke, LM, Chow, CK 2003. Copper toxicity, oxidative stress, and antioxidant nutrients. Toxicology 189, 147–163.CrossRefGoogle ScholarPubMed
García-Vaquero, M, Miranda, M, López-Alonso, M, Castillo, C, Benedito, JL 2011. Evaluation of the need of copper supplementation in intensively reared beef cattle. Livestock Science 137, 273–277.CrossRefGoogle Scholar
Gengelbach, GP, Spears, JW 1998. Effects of dietary copper and molybdenum on copper status, cytokine production and humoral immune response of calves. Journal of Dairy Science 81, 3286–3292.CrossRefGoogle ScholarPubMed
Gooneratne, SR, Howell, JMcC, Gawthorne, J 1979. Intracellular distribution of copper in the liver of normal and copper loaded sheep. Research in Veterinary Science 27, 30–37.CrossRefGoogle ScholarPubMed
Grune, T, Reinheckel, T, Joshi, M, Davies, KJ 1995. Proteolysis in cultured liver epithelial cells during oxidative stress. Role of the multicatalytic proteinase complex, proteasome. Journal of Chemical Biology 270, 2344–2351.CrossRefGoogle ScholarPubMed
Gummow, B 1996. Experimentally induced chronic copper toxicity in cattle. Onderstepoort Journal of Veterinary Research 63, 277–288.Google Scholar
Heijnen, HF, van Donselaar, E, Slot, JW, Fries, DM, Blachard-Fillion, B, Hodara, R, Lightfoot, R, Polydoro, M, Spielberg, D, Thomson, L, Regan, EA, Crapo, J, Ischiropoulos, H 2006. Subcellular localization of tyrosine-nitrated proteins is dictated by reactive oxygen species generating enzymes and by proximity to nitric oxide synthase. Free Radical Biology & Medicine 40, 1903–1913.Google Scholar
Kakkar, P, Jaffery, FN 2005. Biological markers for metal toxicity. Environmental Toxicology and Pharmacology 19, 335–349.CrossRefGoogle ScholarPubMed
Kendall, NR, Illingworth, DV, Telfer, SB 2001. Copper responsive infertility in British cattle: the use of a blood caeruloplasmin to copper ratio in determining a requirement for copper supplementation. In Fertility in the high-producing dairy cow (ed. MG Diskin) British Society of Animal Science, Edinburgh.Google Scholar
Kumaratilake, JS, Howell, JM 1987. Histochemical study of the accumulation of copper in the liver of sheep. Research in Veterinary Science 42, 73–81.Google Scholar
Kwon, OJ, Lee, SM, Floyd, RA, Park, JW 1998. Thiol-dependent metal-catalyzed oxidation of copper, zinc superoxide dismutase. Biochimica et Biophysica Acta Protein Structure and Molecular Enzymology 1387, 249–256.Google Scholar
Laven, RA, Livesey, CT, Offer, NW, Fountain, D 2004. Apparent subclinical hepatopathy due to excess copper intake in lactating Holstein cattle. Veterinary Record 155, 120–121.CrossRefGoogle ScholarPubMed
López-Alonso, M, Prieto, F, Miranda, M, Castillo, C, Hernández, J, Benedito, JL 2005. The role of metallothionein and zinc in hepatic copper accumulation in cattle. The Veterinary Journal 169, 262–267.CrossRefGoogle ScholarPubMed
Luza, SC, Speisky, HC 1996. Liver copper storage and transport during development: implications for cytotoxicity. The American Journal of Clinical Nutrition 63, 812S–820S, http://www.ajcn.org/content/63/5/812S.full.pdf+html Google Scholar
Mauriz, JL, Molpeceres, V, García-Mediavilla, MV, González, P, Barrio, JP, González, JG 2007. Melatonin prevents oxidative stress and changes in antioxidant enzyme expression and activity in the liver of aging rats. Journal of Pineal Research 42, 222–230.Google Scholar
Mercer, JFB 1997. Gene regulation by copper and the basis for copper homeostasis. Nutrition 13, 48–49.Google Scholar
National Research Council (NRC) 2000. Nutrient requirements of beef cattle, 7th edition. National Academy Press, Washington, USA.Google Scholar
Ogihara, H, Ogihara, T, Miki, M, Yasuda, H, Mino, M 1995. Plasma copper and antioxidant status in Wilson's disease. Pediatric Research 37, 219–226.CrossRefGoogle ScholarPubMed
Ozcelik, D, Uzun, H 2009. Copper intoxication; antioxidant defenses and oxidative damage in rat brain. Biological Trace Element Research 127, 45–52.Google Scholar
Pan, YJ, Loo, G 2000. Effect of copper deficiency on oxidative DNA damage in Jurkat T-lymphocytes. Free Radical Biology & Medicine 28, 824–830.CrossRefGoogle ScholarPubMed
Perrin, DJ, Schiefer, B, Blakley, BR 1990. Chronic copper toxicity in a dairy herd. The Canadian Veterinary Journal 31, 629–632.Google Scholar
Puls, R 1994. Mineral levels in animal health, 2nd edition. Clearbook, Sherpa International, British Columbia.Google Scholar
Raisbeck, MF, Siemion, RS, Smith, MA 2006. Modest copper supplementation blocks molybdenosis in cattle. Journal of Veterinary Diagnosis Investigation 18, 566–572.Google Scholar
Ramirez, CE, Mattioli, GA, Tittarelli, CM, Giuliodori, MJ, Yano, H 1998. Cattle hypocuprosis in Argentina associated with periodically flooded soils. Livestock Production Science 55, 47–52.Google Scholar
Rana, SV 2008. Metals and apoptosis: recent developments. Journal of Trace Elements in Medicine and Biology 22, 262–284.CrossRefGoogle ScholarPubMed
Ross, MH, Pawlina, W 2006. Histology. A text and atlas with correlated cell and molecular biology, 5th edition. Lippincott & Wilkins, Inc., EEUU.Google Scholar
Roy, DN, Mandal, S, Sen, G, Biswas, T 2009. Superoxide anion mediated mitochondrial dysfunction leads to hepatocyte apoptosis preferentially in the periportal region during copper toxicity in rats. Chemico-Biological Interactions 182, 136–147.Google Scholar
Suttle, NF 2010. Mineral nutrition of livestock, 4th edition. CABI Publishing, UK.Google Scholar
Uauy, R, Olivares, M, Gonzalez, M 1998. Essentiality of copper in humans. The American Journal of Clinical Nutrition 67 (Suppl. 5), 952S–959S.CrossRefGoogle ScholarPubMed
VLA Surveillance Report 2001. July sees an increased incidence of copper poisoning in cattle. Veterinary Record 149, 257–260.Google Scholar
Walker, CH 1998. Biomarker strategies to evaluate the environmental effects of chemicals. Environmental Health Perspectives 106, 613–620.Google Scholar
Ward, JD, Spears, J 1997. Long-term effects of consumption of low-copper diets with or without supplemental molybdenum on copper status, performance and carcass characteristics of cattle. Journal of Animal Science 75, 3057–3065.CrossRefGoogle ScholarPubMed
Wätjen, W, Beyersmann, D 2004. Cadmium-induced apoptosis in C6 glioma cells: influence of oxidative stress. BioMetals 17, 65–78.Google Scholar
Woo, M, Hakem, A, Elia, AJ, Hakem, R, Duncan, G, Patterson, BJ, Mak, TW 1999. In vivo evidence that caspase-3 is required for Fas-mediated apoptosis of hepatocytes. Journal of Immunology 163, 4909–4916.CrossRefGoogle ScholarPubMed
Xu, J, Ji, LD, Xu, H 2006. Lead-induced apoptosis in PC 12 cells: involvement of p53, Bcl-2 family and caspase-3. Toxicology Letters 166, 160–167.CrossRefGoogle ScholarPubMed
Yamada, T, Sogawa, K, Suzuki, Y, Izumi, K, Agui, T, Matsumoto, K 1992. Elevation of the level of lipid peroxidation associated with hepatic injury in LEC mutant rat. Research Communications in Chemical Pathology and Pharmacology 77, 121–124.Google ScholarPubMed
Yoshida, M, Saegusa, Y, Fukuda, A, Akama, Y, Owada, S 2005. Measurement of radical-scavenging ability in hepatic metallothionein of rat using in vivo electron spins resonance spectroscopy. Toxicology 213, 74–80.Google Scholar
Yu, DY, Li, WF, Deng, B, Mao, XF 2008. Effects of lead on hepatic antioxidant status and transcription of superoxide dismutase gene in pigs. Biological Trace Element Research 126, 121–128.Google Scholar
Zhang, SS, Noordin, MM, Rahman, SO, Haron, J 2000. Effects of copper overload on hepatic lipid peroxidation and antioxidant defense in rats. Veterinary and Human Toxicology 42, 261–264.Google Scholar