Abstract
The European rabbit (Oryctolagus cuniculus) is one of the most important vertebrate species in the Mediterranean Basin ecosystem. Over the last 60 years, the arrival of two viral diseases, myxomatosis and rabbit haemorrhagic disease, have led to dramatic declines in wild rabbit populations across the Iberian Peninsula. These diseases are currently endemic. Periodic outbreaks occur and have significant impacts on wild populations. Both infection types have diverse physiological effects on their hosts that are rooted in aerobic metabolic processes. To fight off these viruses, rabbits activate their immune systems. However, the production of immune defences generates reactive oxygen species that may consequently damage host tissues. Hypothesising that immune responses increase oxidative stress, we examined whether wild rabbits naturally infected with myxoma virus (MV) and rabbit haemorrhagic disease virus (RHDV) had high oxidative stress. Using blood samples, we measured anti-MV and anti-RHDV antibody concentrations and different oxidative stress markers (i.e., glutathione peroxidase, glutathione reductase, superoxide dismutase, catalase, and malondialdehyde). Our results show that rabbits that were seropositive for both MV and RHDV had high concentrations of malondialdehyde. Age and body condition were also positively related to dual seropositivity. No significant relationships were observed between serostatus and the concentrations of the other oxidative stress markers. Although we expected infection with MV and RHDV to be correlated with oxidative stress, the influence of external sources of oxidative stress (e.g., climatic conditions) likely made it more difficult to detect such relationships in wild rabbits.
Similar content being viewed by others
Abbreviations
- ROS:
-
Reactive oxygen species
- OS:
-
Oxidative stress
- AOX:
-
Antioxidant
- MV:
-
Myxoma virus
- RHD:
-
Rabbit haemorrhagic disease
- RHDV:
-
Rabbit haemorrhagic disease virus
- GPX:
-
Glutathione peroxidase
- GR:
-
Glutathione reductase
- SOD:
-
Superoxide dismutase
- CAT:
-
Catalase
- MDA:
-
Malondialdehyde
References
Alves P, Moreno S (1996) Estudo da reprodução do coelho-bravo (Oryctolagus cuniculus) em Portugal. Rev Florestal 9:149–166
Apel K, Hirt H (2004) Reactive oxygen species: metabolism, oxidative stress, and signal transduction. Annu Rev Plant Biol 55:373–399
Beckman KB, Ames BN (1998) The free radical theory of aging matures. Physiol Rev 78:547–581
Bertó-Moran A, Pacios I, Serrano E, Moreno S, Rouco C (2013) Coccidian and nematode infections influence prevalence of antibody to myxoma and rabbit hemorrhagic disease viruses in European rabbits. J Wildl Dis 49:10–17
Buege JA, Aust SD (1978) Microsomal lipid peroxidation. Methods Enzymol 52:302–310
Calvete C, Estrada R, Villafuerte R, Osácar JJ, Lucientes J (2002) Epidemiology of viral haemorrhagic disease and myxomatosis in a free-living population of wild rabbits. Vet Rec 150:776–781
Cameron CM, Barrett JW, Liu L, Lucas AR, McFadden G (2005a) Myxoma virus M141R expresses a viral CD200 (vOX-2) that is responsible for down-regulation of macrophage and T-cell activation in vivo. J Virol 79:6052–6067
Cameron CM, Barrett JW, Mann M, Lucas A, McFadden G (2005b) Myxoma virus M128L is expressed as a cell surface CD47-like virulence factor that contributes to the downregulation of macrophage activation in vivo. Virology 337:55–67
Carmagnol F, Sinet PM, Jerome H (1983) Selenium-dependent and non-selenium-dependent glutathione peroxidases in human tissue extracts. Biochim Biophys Acta 759:49–57
Christensen LL, Selman C, Blount JD, Pilkington JG, Watt KA, Pemberton JM, Reid JM, Nussey DH (2015) Plasma markers of oxidative stress are uncorrelated in a wild mammal. Ecol Evol 5:5096–5108
Clarkson PM, Thompson HS (2000) Antioxidants: what role do they play in physical activity and health? Am J Clin Nutr 72:637s–646s
Cohen AA, McGraw KJ (2009) No simple measures for antioxidant status in birds: complexity in inter-and intraspecific correlations among circulating antioxidant types. Funct Ecol 23:310–320
Cohen G, Somerson NL (1969) Glucose-dependent secretion and destruction of hydrogen peroxide by mycoplasma pneumoniae. J Bacteriol 98:547–551
Costantini D (2008) Oxidative stress in ecology and evolution: lessons from avian studies. Ecol Lett 11:1238–1251
Costantini D, Dell’Omo G, De Filippis PS, Marquez C, Snell H, Snell H, Tapia W, Brambilla G, Gentile G, (2009) Temporal and spatial covariation of gender and oxidative stress in the Galápagos land iguana Conolophus subcristatus. Physiol Biochem Zool 82:430–437
Costantini D (2014) Oxidative stress and hormesis in evolutionary ecology and physiology. A marriage between mechanistic and evolutionary approaches. Springer, Berlin
Costantini D, Møller AP (2009) Does immune response cause oxidative stress in birds? A meta-analysis. Comp Biochem Physiol A 153:339–344
Costantini D, Verhulst S (2009) Does high antioxidant capacity indicate low oxidative stress? Funct Ecol 23:506–509
Cribb AE, Leeder JS, Spielberg SP (1989) Use of a microplate reader in an assay of glutathione reductase using 5, 50-dithiobis (2-nitrobenzoic acid). Anal Biochem 183:195–196
Dowling DK, Simmons LW (2009) Reactive oxygen species as universal constraints in life-history evolution. Proc R Soc Lond B Biol Sci 276:1737–1745
Evans GO (2008) Animal hematotoxicology: a practical guide for toxicologists and biomedical researchers. CRC Press
Foyer CH, Noctor G (2005) Oxidant and antioxidant signalling in plants: a re-evaluation of the concept of oxidative stress in a physiological context. Plant Cell Environ 28:1056–1071
García-Bocanegra I, Astorga RJ, Napp S, Casal J, Huerta B, Borge C, Arenas A (2010) Myxomatosis in wild rabbit: design of control programs in Mediterranean ecosystems. Prev Vet Med 93:42–50
Gassó D, Vicente J, Mentaberre G, Soriguer R, Rodríguez RJ, Navarro-González N, Tvarijonaviciute A, Lavín S, Fernández-Llario P, Segalés J, Serrano E (2016) Oxidative stress in wild boars naturally and experimentally infected with Mycobacterium bovis. PLoS One 11:e0163971
Gechev TS, Van Breusegem F, Stone JM, Denev I, Laloi C (2006) Reactive oxygen species as signals that modulate plant stress responses and programmed cell death. BioEssays 28:1091–1101
Gibbs HL, Chiucchi JE (2012) Inbreeding, body condition, and heterozygosity-fitness correlations in isolated populations of the endangered eastern massasauga rattlesnake (Sistrurus c. Catenatus). Conserv Genet 13:1133–1143
Halliwell B, Gutteridge JMC (1999) The chemistry of free radicals and related ‘reactive species’. Free Radic Biol Med 3:1–7
Halliwell BH, Gutteridge JMC (2007) Free radicals in biology and medicine, 4th edn. Oxford University Press, Oxford
Harman E (1956) Protein oxidation in aging and age-related diseases. Gerontology 11:298–300
Hulbert AJ, Pamplona R, Buffenstein R, Buttemer WA (2007) Life and death: metabolic rate, membrane composition, and life span of animals. Physiol Rev 87:1175–1213
Johnston JB, Barrett JW, Chang W, Chung C-S, Zeng W, Masters J, Mann M, Wang F, Cao J, McFadden G (2003) Role of the serine-threonine kinase PAK-1 in myxoma virus replication. J Virol 77:5877–5888
Kerr PJ (2012) Myxomatosis in Australia and Europe: a model for emerging infectious diseases. Antivir Res 93:387–415
Kerr PJ, McFadden G (2002) Immune responses to myxoma virus. Viral Immunol 15:229–246
Lastra RG (2009) Mecanismos moleculares implicados en la fisiopatología de la enfermedad hemorrágica del conejo, un modelo animal de fallo hepático fulminante. Doctoral dissertation, Universidad de León
Legendre P (2008) lmodel2: Model II Regression. R package version 1.6–3
Lochmiller RL, Deerenberg C (2000) Trade-offs in evolutionary immunology: just what is the cost of immunity? Oikos 88:87–98
Maceda-Veiga A, Figuerola J, Martínez-Silvestre A, Viscor G, Ferrari N, Pacheco M (2015) Inside the Redbox: applications of haematology in wildlife monitoring and ecosystem health assessment. Sci Total Environ 514:322–332
Marri V, Richner H (2015) Immune response, oxidative stress and dietary antioxidants in great tit nestlings. Comp Biochem Physiol A 179:192–196
Masters J, Hinek AA, Uddin S, Platanias LC, Zeng W, McFadden G, Fish EN (2001) Poxvirus infection rapidly activates tyrosine kinase signal transduction. J Biol Chem 276:48371–48375
McCord JM, Fridovich I (1969) Superoxide dismutase. An enzymic function for erythrocuprein (hemocuprein). J Biol Chem 244:6049–6055
Monaghan P, Metcalfe NB, Torres R (2009) Oxidative stress as a mediator of life history trade-offs: mechanisms, measurements and interpretation. Ecol Lett 12:75–92
Norte AC, Ramos JA, Sousa JP, Sheldon BC (2009) Variation of adult great tit Parus major body condition and blood parameters in relation to sex, age, year and season. J Ornithol 150:651–660
Nussey DH, Pemberton JM, Pilkington JG, Blount JD (2009) Life history correlates of oxidative damage in a free-living mammal population. Funct Ecol 23:809–817
Pacios-Palma I, Santoro S, Bertó-Moran A, Moreno S, Rouco C (2016) Effects of myxoma virus and rabbit hemorrhagic disease virus on the physiological condition of wild European rabbits: is blood biochemistry a useful monitoring tool? Res Vet Sci 109:129–134
Pap PL, Sesarman A, Vágási CI, Buehler DM, Pătraş L, Versteegh MA, Banciu M (2014) No evidence for parasitism-linked changes in immune function or oxidative physiology over the annual cycle of an avian species. Physiol Biochem Zool 87:729–739
Peig J, Green AJ (2009) New perspectives for estimating body condition from mass/length data: the scaled mass index as an alternative method. Oikos 118:1883–1891
Prior RL, Cao G (1999) In vivo total antioxidant capacity: comparison of different analytical methods 1. Free Radic Biol Med 27:1173–1181
R Core Team (2016) R: a language and environment for statistical computing. R Foundation for Statistical Computing, Vienna URL https://www.R-project.org/
Raja-aho S, Kanerva M, Eeva T, Lehikoinen E, Suorsa P, Gao K, Vosloo D, Nikinmaa M (2012) Seasonal variation in the regulation of redox state and some biotransformation enzyme activities in the barn swallow (Hirundo rustica L.). Physiol Biochem Zool 85:148–158
Rouco C, Ferreras P, Castro F, Villafuerte R (2008) The effect of exclusion of terrestrial predators on short-term survival of translocated European wild rabbits. Wildl Res 35:625–632
Rouco C, Villafuerte R, Castro F, Ferreras P (2011) Effect of artificial warren size on a restocked European wild rabbit population. Anim Conserv 14:117–123
Rubolini D, Colombo G, Ambrosini R, Caprioli M, Clerici M, Colombo R, Dalle-Donne I, Milzani A, Romano A, Romano M, Saino N (2012) Sex-related effects of reproduction on biomarkers of oxidative damage in free-living barn swallows (Hirundo rustica). PLoS One 7:e48955
Sanchez-Campos S, Alvarez M, Culebras JM, Gonzalez-Gallego J, Tunon MJ (2004) Pathogenic molecular mechanisms in an animal model of fulminant hepatic failure: rabbit hemorrhagic viral disease. J Lab Clin Med 144:215–222
Schneeberger K, Czirják GÁ, Voigt CC (2013) Inflammatory challenge increases measures of oxidative stress in a free-ranging, long-lived mammal. J Exp Biol 216:4514–4519
Selman C, Blount JD, Nussey DH, Speakman JR (2012) Oxidative damage, ageing, and life-history evolution: where now? Trends Ecol Evol 27:570–577
Sies H (1991) Oxidative stress: from basic research to clinical application. Am J Med 91:S31–S38
Sorci G, Faivre B (2009) Inflammation and oxidative stress in vertebrate host-parasite systems. Philos Trans R Soc B 364:71–83
Tanchev S, Gadjeva V, Stanilova S (2003) Influence of antigen stimulation on the oxidative stress parameters in outbred and inbred rabbits. Arch Physiol Biochem 111:437–442
Tunon MJ, Sanchez-Campos S, Garcia-Ferreras J, Alvarez M, Jorquera F, Gonzalez-Gallego J (2003) Rabbit hemorrhagic viral disease: characterization of a new animal model of fulminant liver failure. J Lab Clin Med 141:272–278
Vallejo D, Crespo I, San-Miguel B, Álvarez M, Prieto J, Tuñón MJ, González-Gallego J (2014) Autophagic response in the rabbit hemorrhagic disease, an animal model of virally-induced fulminant hepatic failure. Vet Res 45:15
van de Crommenacker J, Horrocks NP, Versteegh MA, Komdeur J, Tieleman BI, Matson KD (2010) Effects of immune supplementation and immune challenge on oxidative status and physiology in a model bird: implications for ecologists. J Exp Biol 213:3527–3535
Villafuerte R (1994) Riesgo de predación y estrategias defensivas del conejo en el Parque Nacional de Doñana. Doctoral dissertation. Universidad de Córdoba
Villafuerte R, Castro F, Ramírez E, Cotilla I, Parra F, Delibes-Mateos M, Recuerda P, Rouco C (2017) Large-scale assessment of myxomatosis prevalence in European wild rabbits (Oryctolagus cuniculus) 60 years after first outbreak in Spain. Res Vet Sci 114:281–286
von Schantz T, Bensch S, Grahn M, Hasselquist D, Wittzell H (2016) Good genes, oxidative stress and condition-dependent sexual signals. Proc R Soc Lond Ser B Biol Sci 266:1–12
Acknowledgements
Isabel Pacios Palma was supported by a predoctoral Severo Ochoa grant from the Spanish Ministry of Economy and Competitiveness, through the Severo Ochoa Program for Centers of Excellence in R+D+I (SEV-2012-0262). Carlos Rouco was funded by XXII Propio de Investigación of the University of Córdoba and “Programa Operativo de fondos FEDER Andalucía”. Special thanks to J. Pearce (www.englishservicesforscientists.com) for her language editing services and to Dr. Alberto Maceda-Veiga and Laura Rios Pena for their helpful comments, which improved the manuscript. Finally, thanks to V. Morlanes, C. Marfil, G. Macías, and A. Bertó for their assistance in the field.
Author information
Authors and Affiliations
Corresponding author
Ethics declarations
All animal experimentation was carried out in accordance with Spanish and European regulations (Law 32/2007, Council Directive 2010/63/EU, R.D. 53/2013, ECC/566/2015).
Electronic supplementary material
ESM 1
(DOCX 21 kb)
Rights and permissions
About this article
Cite this article
Pacios-Palma, I., Moreno, S., Selman, C. et al. Oxidative stress in wild European rabbits naturally infected with myxoma virus and rabbit haemorrhagic disease virus. Eur J Wildl Res 64, 47 (2018). https://doi.org/10.1007/s10344-018-1203-0
Received:
Revised:
Accepted:
Published:
DOI: https://doi.org/10.1007/s10344-018-1203-0