The effect of patulin on femoral bone structure in male rabbits


  • Veronika Kováčová Constantine the Philosopher University, Faculty of Natural Sciences, Department of Zoology and Anthropology, 949 74 Nitra
  • Hana Ďúranová Constantine the Philosopher University, Faculty of Natural Sciences, Department of Zoology and Anthropology, 949 74 Nitra
  • Ramona Babosová Constantine the Philosopher University, Faculty of Natural Sciences, Department of Zoology and Anthropology, 949 74 Nitra
  • Radoslav Omelka Constantine the Philosopher University, Faculty of Natural Sciences, Department of Botany and Genetics, 949 74 Nitra
  • Vladimí­ra Krajčovičová Constantine the Philosopher University, Faculty of Natural Sciences, Department of Botany and Genetics, 949 74 Nitra
  • Robert Stawarz Robert Stawarz, Krakow Pedagogical University, Institute of Biology, 31 054 Krakow
  • Marcela Capcarová Slovak University of Agriculture, Department of Animal Physiology, 949 76 Nitra
  • Monika Martiniaková Constantine the Philosopher University, Faculty of Natural Sciences, Department of Zoology and Anthropology, 949 74 Nitra



patulin, femoral bone, rabbit, histomorphometry


A lot of kinds of crops are susceptible to fungal attack, leading to considerable financial losses and damage the health of humans and animals. Patulin, a toxic fungal metabolite, can be found mainly in apple and apple products, with much less frequent contamination in other food products. Because of its high incidence and harmful health effects, patulin belongs to a class of mycotoxins, which are strictly monitored. However, its effect on bone structure is still unknown. This study was designed to investigate the impact of patulin on femoral bone structure in adult male rabbits. Four month-old male rabbits were randomly divided into two groups of three animals each. Rabbits from the experimental group (group A, n=3) were intramuscularly administered with patulin at dose 10 μ body weight (b.w.) twice a week for 4 weeks. The second group without patulin administration served as a control (group B, n=3). At the end of the experiment, body weight, femoral weight and length, cortical bone thickness and histological structure of femoral bones from all rabbits were determined. The results did not show any significant differences in body weight, femoral weight and length between experimental and control groups of rabbits. On the other hand, intramuscular application of patulin induced a significant increase in cortical bone thickness (<0.05) and considerable changes in qualitative histological characteristics of compact bone in adult male rabbits. In patulin-intoxicated males, the primary vascular longitudinal bone tissue was absent near endosteal border. On the other hand, this tissue occurred near periosteum and also in the middle part of the femoral bone in these rabbits. The values for the primary osteons' vascular canals were significantly lower (<0.05) in males exposed to patulin as compared to the control group. Based on these findings we can conclude that intramuscular patulin administration demonstrably influences cortical bone thickness and histological structure of femoral bone in adult male rabbits.


Download data is not yet available.


Akishita, M., Yu, J. 2012. Hormonal effects on blood vessels. Hypertens Res., vol. 35, no. 4, p. 363-369. PMid: 22297478

Al-Hazmi, M. A. 2012. Patulin in apple juice and its risk assessments on albino mice. Toxicol Ind Health, vol. 25, no. 30, p. 534-545. PMid:23012343

Alexa, E., Dehelean, C. A., Poiana, M. A., Radulov, I., Cimpean, A. M., Bordean, D. M., Tulcan, C., Pop, G. 2013. The occurrence of mycotoxins in wheat from western Romania and histopathological impact as effect of feed intake. Chemistry Central Journal, vol. 7, p. 1-11. PMid:23759114

Baek, K. H., Oh, K. W., Lee, W. Y., Lee, S. S., Kim, M. K., Kwon, H. S., Rhee, E. J., Han, J. H., Song, K. H., Cha, B. Y., Lee, K. W., Kang, M. I. 2010. Association of oxidative stress with postmenopausal osteoporosis and the effects of hydrogen peroxide on osteoclast formation in human bone marrow cell cultures. Calcif Tissue Int., vol. 87, p. 226-235. PMid: 20614110

Becci, P. J., Hess, F. G., Johnson, W. D., Gallo, M. A., Babish, J. G., Dailey, R. E., Parent, R. A. 1981. Long-term carcinogenicity and toxicity studies of patulin in the rat. J. Appl. Toxicol., vol. 1, no. 5, p. 256-261. PMid: 6821081

Beltrán, E., Ibáñez, M., Sancho, J. V., Hernández, F. 2014. Determination of patulin in apple and derived products by UHPLC-MS/MS. Study of matrix effects with atmospheric pressure ionisation sources. Food Chem., vol. 142, p. 400-407. PMid: 24001858

Bennett, J. W., Klich, M. 2003. Mycotoxins. Clin. Microbiol. Rev., vol. 16, no. 3, p. 497-516. PMC: 164220

Braverman, L. E., Werner, S. C., Ingbar, S. H., Utiger, R. D. 2005. Werner & Ingbar's the Thyroid: A Fundamental and Clinical Text. USA: Lippincott Williams & Wilkins, 1100 p., ISBN 0-7817-5047-4.

Broom, W. A., Bülbring, E., Chapman, C. J., Hampton, J. W. F., Thomson, A. M., Ungar, J., Wien, R., Woolfe, G. 1944. The Pharmacology of patulin. Br. J. Exp. Pathol, vol. 25, no. 6, p. 195-207. PMC: 2065635

Bryden, W. L. 2007. Mycotoxins in the food chain: human health implications. Asia Pac. J. Clin. Nutr., vol. 16, p. 95-101. PMid: 17392084

Burr, D. B., Guillot, G. M. 2012. Almost invisible, often ignored: periosteum, the living place of bone. Medicographia, vol. 34, p. 221-227. [cit. 2014-02-13] Available at:

Callewaert, F., Boonen, S., Vanderschueren, D. 2010. Sex steroids and the male skeleton: a tale of two hormones. Trends Endocrinol. Metab., vol. 21, no. 2, p. 89-95. PMid: 19837603

Cilotti, A., Falchetti, A. 2009. Male osteoporosis and androgenic therapy: from testosterone to SARMs. Clin Cases Miner Bone Metab., vol. 6, no. 3, p. 229-233. PMC: 2811355

Dempster, D. W., Cosman, F., Kurland, E. S., Zhou, H., Nieves, J., Woelfert, L., Shane, E., Plavetić, K., Müller, R., Bilezikian, J., Lindsay, R. 2001. Effects of daily treatment with parathyroid hormone on bone microarchitecture and turnover in patients with osteoporosis: a paired biopsy study. J. Bone Miner. Res., vol. 16, no. 10, p. 1846-1853. PMid: 11585349

Devegowda, G., Ravikiran, D. 2008. Mycotoxins and eggshell quality: cracking the problem. World

Mycotoxin J, vol. 1, no. 2, 203-208.

Enlow, D. H., Brown, S. O. 1956. A comparative histological study of fossil and recent bone tissues. Part I.

Tex. J. Sci., vol. 8, p. 405-412.

Fernández-Cruz, M. L., Mansilla, M. L., Tadeo, J. L. 2010. Mycotoxins in fruits and their processed products: Analysis, occurrence and health implications. J. Adv. Res., vol. 1, no. 2, p. 113-122.

Food and Agriculture Organization (FAO): Worldwide Regulation for Mycotoxins in Food and Feed in 2003. FAO Food and Nutrition Papers 81. Rome: FAO; 2004.

Gimeno, A., Martins, M. L. 2006. Mycotoxins and Mycotoxicosis in Animals and Humans. USA: Special Nutrients, Inc., 127 p.

Glahn, R. P., Beers, K. W., Bottje, W. G., Widerman R. F. Jr., Huff, W. E., Thomas, W. 1991. Aflatoxicosis alters avian renal function, calcium, and vitamin D metabolism. J. Toxicol. Environ. Health., vol. 34, no. 3, p. 309-321. PMid: 1942121

Glaser, N., Stopper, H. 2012. Patulin: Mechanism of genotoxicity. Food Chem. Toxicol., vol. 50, no. 5, p. 1796-1801. PMid: 22425938

González-Osnaya, L., Soriano, J. M., Moltó, J. C., Mañez, J. 2007. Exposure assessment to patulin from the consumption of apple-based products. Food Addit. Contam., vol. 24, no. 11, p. 1-21.

Gorton, R. N., Buth, J., Spade, D. 2005. Medical Therapy and Health Maintenance for Transgender Men: A Guide For Health Care Providers. San Francisco, CA: Lyon-Martin Women's Health Services. p. 98, ISBN 0-9773250-0-8.

Greenlee, D. M., Dunnell, R. C. 2010. Identification of fragmentary bone from the Pacific. J. Archaeol. Sci., vol. 37, no. 5, p. 957-970.

Hopmans, E. C. 1997. Patulin: a mycotoxin in apples. Perishables Handling Quarterly, no. 91, p. 5-6.

Hosseini, S. S., Bagheri, R. 2012. Some major mycotoxin and their mycotoxicoses in nuts and dried fruits. Intl. J. Agron. Plant. Prod., vol. 3, no. 5, p. 179-184. [cit. 2014-02-7] Available at:

Chrenek, P., Bátorová, A., Bauer, M., Bauerová, M., Bulla, J., Dragin, S., Fabiš, M., Foltýs, V., Gažovičová, Z., Grosskopf, B., Hanusová, E., Hetényi, L., Chrastinová, Ľ., Jurčík, R., Kačmárik, J., Kirchnerová, K., Kubovičová, E., Kuklová, Ž., Lukáč, N., Makarevič, A., Martiniaková, M., Massányi, P., Novotná, K., Omelka, R., Paleyanda, R., Parkányi, V., Peškovičová, D., Pivko, J., Popelková, M., Rafay, J., Ryban, L., Sirotkin, A., Süvegová, K., Trandžík, J., Vondráková, M., Žilka, N. 2006. Produkcia a analýza transgénnych králikov. (The production and analysis of transgenic rabbits) 1st ed. Nitra: SCPV v Garmond, 237 p., ISBN 80-88872-54-5.

Ionescu, V., Catana, M., Catana, L., Negoita, M., Iorga, E., Balea, A., Campeanu, G. 2010. Evaluation of patulin contamination of apple juice, using high performance liquid chromatography. Chem Bull „POLITEHNICA" Univ. (Timisoara), vol. 55, no. 69, p. 186-188.

[cit. 2014-02-13] Available at:

Jay, J. M. 2000. Modern Food Microbiology - Sixth Edition. USA: Aspen Publishers, Inc., p. 720 ISBN 0-8342-1671-X.

Jilka, R. L., Weinstein, R. S., Bellido, T., Roberson, P., Parfitt, A. M., Manolagas, S. C. 1999. Increased bone formation by prevention of osteoblast apoptosis with parathyroid hormone. J. Clin. Invest., vol. 104, no. 4,

p. 439-446.

Kung, A. W. C. 2003. Androgen and bone mass in men. Asian J. Androl., vol. 5, p. 148-154. PMid: 12778327

Lieberman, J. R., Friedlaender, G. E. 2005. Bone Regeneration and Repair: Biology and Clinical Applications. USA: New Jersey: Humana Press Inc., 398 p. ISBN 0-89603-847-5.

Lips, P. 2001. Vitamin D deficiency and secondary hyperparathyroidism in the elderly: consequences for bone loss and fractures and therapeutic implications. Endocr. Rev., vol. 22, no. 4, p. 477-501. PMid: 11493580

Liu, B. H., Wu, T. S., Yu, F. Y., Su, C. C. 2007. Induction of oxidative stress response by the mycotoxin patulin in mammalian cells. Toxicol. Sci., vol. 95, no. 2, p. 340-347. PMid: 17090621

Llewellyn, G. C., McCay, J. A., Brown, R. D., Musgrove, D. L., Butterworth, L. F., Munson, A. E., White, K. L. jr. 1998. Immunological evaluation of the mycotoxin patulin in female B6C3F1 mice. Food Chem. Toxicol., vol. 36, no. 12, p. 1107-1015. PMid: 9862653

Magan, N., Olsen, M., Kuiper-Goodman, T., Arcella, D., Leclercq, C., Van Egmond, H. P., Jonker, M. A., Whitaker, T. B., Patel, P., Nicholson, P. - Aldred, D., Sanchis, V., Shapira, R., Scudamore, K. A., Battilani, P., Pietri, A., Pettersson, H., Aish, J. L., Rippon, E. H., Barlow, T., Hattersley, S. J . 2004. Mycotoxins in Food: Detection and Control. England: Woodhead Publishing Limited, 488 p. ISBN 0-8493-2557-9.

Martiniaková, M., Vondráková, M., Fabiš, M. 2003. Investigation of the microscopic structure of rabbit compact bone tissue. Scripta medica (Brno), vol. 76, no. 4, p. 215-220.

Martiniaková, M., Omelka, R., Grosskopf, B., Sirotkin, A. V., Chrenek, P. 2008. Sex-related variation in compact bone microstructure of the femoral diaphysis in juvenile rabbits. Acta Veterinaria Scandinavica, vol. 50, p. 15. PMid:18522730

Martiniaková, M., Omelka, R., Jančová, A., Stawarz, R., Formicki, G. 2010. Heavy metal content in the femora of yellow-necked mouse (Apodemus flavicollis) and wood mouse (Apodemus sylvaticus) from different types of polluted environment in Slovakia. Environ. Monit. Assess., vol. 171, no. 1-4, p. 651-660. PMid: 20135219

Martiniaková, M., Chovancová, H., Boboňová, I., Omelka, R. 2013. Účinky rizikových látok na štruktúru kostného tkaniva potkanov. (The effects of risk substances on the bone tissue structure in rats) Nitra: Faculty of Natural Sciences, UKF, 187 p. ISBN 978-80-558-0295-4.

Moake, M. M., Padilla-Zakour, O. I., Worobo, R. W. 2005. Comprehensive Review of Patulin Control Methods in Foods. Compr. Rev. Food Sci. F., vol. 1, p. 8-21.

Özsoy, N., Selmanoğlu, G., Koçkaya, E. A., Gül, N., Cebesoy, S. 2008. Effect of patulin on the interdigitating dendritic cells (IDCs) of rat thymus. Cell Biochem Funct, vol. 26, no. 2, p. 192-196. PMid: 17702051

Notelovitz, M. 2002. Androgen effects on bone and muscle. Fertil Steril., vol. 77, suppl. 4, p. 34-41. PMid: 12007900

Peraica, M., Radić, B., Lucić, A., Pavlović, M. 1999. Toxic effects of mycotoxins in humans. B World Health Organ, vol. 77, p. 754-766. PMC2557730

Piqué, E., Vargas-Murga, L., Gómez-Catalán, J., Llobet, J. M. 2013. Occurrence of patulin in organic and conventional apple juice. Risk assessment. Recent Advances in Pharmaceutical Sciences III, Transworld Research Network, p. 131-144 ISBN: 978-81-7895-605-3.

Puel, O., Galtier, P., Oswald, I. P. 2010. Biosynthesis and toxicological effects of patulin. Toxins (Basel), vol. 2, no. 4, p. 613-631.

Rhee, Y., Allen, M. R., Condon, K., Lezcano, V., Ronda, A. C., Galli, C., Olivos, N., Passeri, G., O'Brien, C. A., Bivi, N, Plotkin L. I., Bellido, T. 2011. PTH receptor signaling in osteocytes governs periosteal bone formation and intracortical remodeling. J. Bone Miner. Res., vol. 26, no. 5, p. 1035-1046. PMid: 21140374

Ricqlès, A. J., Meunier, F. J., Castanet, J., Francillon-Vieillot, H. 1991. Comparative microstructure of bone. Bone 3, Bone Matrix and Bone Specific Products. Hall BK. Boca Raton: CRC Press; p. 1-78. ISBN 0-8493-8823-6.

Riggs, B. L., Melton III, L. J., Robb, R. A., Camp, J. J., Atkinson, E. J., Peterson, J. M., Rouleau, P. A., McCollough, C. H., Bouxsein, M. L., Khosla, S. 2004. Population-based study of age and sex differences in bone volumetric density, size, geometry, and structure at different skeletal sites. J. Bone Miner. Res., vol. 19, no. 12, p. 1945-1954. PMid: 15537436

Sato, M., Vahle, J., Schmidt, A., Westmore, M., Smith, S., Rowley, E., Ma, L. Y. 2002. Abnormal bone architecture and biomechanical properties with near-lifetime treatment of rats with PTH. Endocrinology, vol. 143, no. 9, p. 3230-3242. PMid: 12193534

Seeman, E. 2003. Periosteal bone formation - a neglected determinant of bone strenght. N. Engl. J. Med., vol. 349, no. 4, p. 320-323. PMid: 12878736

Selmanoğlu, G. 2006. Evaluation of the reproductive toxicity of patulin in growing male rats. Food Chem. Toxicol., vol. 44, no. 12, p. 2019-2024. PMid: 16905234

Selmanoglu, G., Koçkaya, E. A. 2004. Investigation of the effects of patulin on thyroid and testis, and hormone levels in growing male rats. Food Chem. Toxicol., vol. 42, no. 5, p. 721-727. PMid: 15046817

Sergeev, I. N., Arkhapchev I. u. P., Kravchenko, L. V., Kodentsova V. M., Piliia, N. M. 1988. Effect of mycotoxins aflatoxin B1 and T-2 toxin on the vitamin D3 metabolism and binding of its hormonal form 1,25-dihydroxyvitamin D3 in rats. Vopr. Med. Khim., vol. 34, no. 4, p. 51-57. PMid: 2848363

Szulc, P., Seeman, E., Duboeuf, F., Sornay-Rendu, E., Delmas, P. D. 2006. Bone fragility: failure of periosteal apposition to compensate for increased endocortical resorption in postmenopausal women. J. Bone Miner. Res., vol. 21, no. 12, p. 1856-1863. PMid: 17002580

Teiltelbaum, S. L. 2000. Bone resorption by osteoclasts. Science, vol. 289, no. 5484, p. 1504-1508. PMid: 10968780

Tuck, S. P. Francis, R. M. 2009. Testosterone, bone and osteoporosis. In: Jones, T. H. Advances in the Management of Testosterone Deficiency. Switzerland: Reinhardt Druck, Basel, Karger, p. 210. ISBN 978-3-8055-8622-1.

Yoopan, N., Watcharasit, P., Wongsawatkul, O., Piyachaturawat, P., Satayavivad, J. 2008. Attenuation of eNOS expression in cadmium-induced hypertensive rats. Toxicol Lett., vol. 176, no. 2, p. 157-161. PMid: 18155860

Zbynovská, K., Emrichová, J., Kalafová, A., Petruška, P., Ondruška, Ľ., Jurčík, R., Chrastinová, Ľ., Kováčik, A., Schneidgenová, M., Tusimová, E., Capcarová, M. 2013. Haematological changes in rabbit's blood after two weeks exposure of patulin. RFFCH Gödöllő, p. 1-5. [cit. 2014-02-19] Available at:




How to Cite

Kováčová, V. ., Ďúranová, H. ., Babosová, R. ., Omelka, R. ., Krajčovičová, V. ., Stawarz, R. ., Capcarová, M. ., & Martiniaková, M. . (2015). The effect of patulin on femoral bone structure in male rabbits. Potravinarstvo Slovak Journal of Food Sciences, 9(1), 112–118.

Most read articles by the same author(s)