Oral and intramuscular application of cyanogenic glycoside amygdalin did not induce changes in haematological profile of male rabbits
Abstract
Amygdalin is a cyanogenic glycoside initially obtained from the seeds of bitter almonds. It is composed of one molecule of benzaldehyde, two molecules of glucose and one molecule of hydrocyanic acid. Various ways of amygdalin application play a different role in recipient organism. Intravenous infusion of amygdalin produced neither cyanidemia nor signs of toxicity, but oral administration resulted in significant blood cyanide levels. The present in vivo study was designed to reveal whether amygdalin is able to cause changes in the haematological profile and thus alter the physiological functions, using rabbits as a biological model. Adult male rabbits (n = 20) were randomly divided into five groups: the control group without any amygdalin administration, two experimental groups received a daily intramuscular injection of amygdalin at a dose 0.6 and 3.0 mg.kg-1 b.w. and other two groups were fed by crushed apricot seeds at dose 60 and 300 mg. kg-1 b.w., mixed with commercial feed over the period of 14 days. After two weeks, haematological parameters in whole blood were analysed (WBC - total white blood cell count, LYM - lymphocytes count, MID - medium size cell count, GRA - granulocytes count, RBC - red blood cell count, HGB - haemoglobin, HCT - haematocrit, MCV - mean corpuscular volume, MCH - mean corpuscular hemoglobin, MCHC - mean corpuscular hemoglobin concentration, RDWc - red cell distribution width, PLT - platelet count, PCT - platelet percentage, MPV - mean platelet volume, PDWc - platelet distribution width) using haematology analyser Abacus junior VET. Our findings indicate that intramuscular and oral application of amygdalin for two weeks did not significantly affect the haematology parameters in experimental animals. In this study, no obvious beneficial or negative effects of amygdalin administration on the blood of male rabbits were observed.
References
Andrew, F., Roscoe, O. B., Anrew, E. G. 1980. A β-glucosidase in feline kidney that hydrolyzes amydalin (Laetrile). Archives of Biochemistry and Biophysics, vol. 201, no. 2, p. 363-368.
Baroni, A., Paolett,i I., Greco, R., Satriano, R. A., Ruocco, E., Tufano, M. A., Perez, J. J. 2005. Immunomodulatory effects of a set of amygdalin analogues in human keratinocyte cells. Experimental Dermatology, vol. 14, no. 11, p. 854-859. https://doi.org/10.1111/j.1600-0625.2005.00368.x PMid:16232308
Calson, I. J. S. 1998. Ethnomedical field research, medicinal plants and tropical public health. Rainforest Med. Bulletin, vol. 5, no. 1, p. 8-15.
CoE, 2000. Council of Europe Committee of Experts on Flavouring Substances 46th meeting-RD 4.13/1-46 data sheet on HCN.
Coles, E. H. 1974. Veterinary clinical pathology. St. LOUIS, USA : W.B. Saunders Company. 615 p. ISBN: 0721626416.
Du, Q., Jerz, G., He, Y., Li, L., Xu, Y., Zhang, Q., Zheng, Q., Winterhalter, P., Ito, Y. 2005. Semi-industrial isolation of salicin and amygdalin from plant extracts using slow rotary counter-current chromatography. Journal of Chromatography A, vol. 107, no. 1-3, p. 43-46. https://doi.org/10.1016/j.chroma.2005.03.064
FAO/WHO (Food and Agricultural Organization/World Health Organization), 2012. Safety evaluation of certain food additives and contaminants prepared by the seventy-fourth meeting of the joint FAO/WHO expert committee.
Fukuda, T., Ito, H., Mukainaka, T., Tokuda, H., Nishino, H., Yoshida, T. 2003. Anti-tumor promoting effect of glycosides from Prunus persica seeds. Biological and Pharmaceutical Bulletin, vol. 26, no. 2, p. 271-273. https://doi.org/10.1248/bpb.26.271 PMid:12576693
Gomez, G., Aparicio, M. A., Wilolhite, C. C. 1988. Relationship between dietary cassava cyanide levels and Brailer performance. Nutrition Reports International, vol. 37, p. 63-75.
Grover, J. K., Yadav, S., Vats, V. 2002. Medicinal plants of India with antidiabetic potential. Journal of Ethnopharmacology, vol. 81, no. 1, p. 81-100. https://doi.org/10.1016/S0378-8741(02)00059-4
Hayes, W. J. 1967. The 90 day LD50 and chronicity factors as a measure of toxicity. Toxicology and Applied Pharmacology, vol. 11, no. 2, p. 327-335. https://doi.org/10.1016/0041-008X(67)90076-2
Henneberg, W., Stohmann, F. 1860-1864. Beiträge zur Begründung einer rationellen Fütterung der Wiederkäuer I & II. Braunschweig. German : Braunschweig.
Cerebral function improver. Patent owner Hiromi, S. Patent no. JP 7,165,589.
Hwang, H. J., Lee, H. J., Kim, Ch. J., Shim, I., Hahm, D. H. 2008. Inhibitory effect of amygdalin on lipopolyccharide-inducible TNF-α and IL-1β mRNA expression and carrageenan-induced rats arthritis. Journal of Microbiology and Biotechnology, vol. 18, no. 10, p. 1641-1647. PMid:18955812
Chang, H. K., Shin, M. S., Yang, H. Y., Lee, J. W., Kim, Y. S., Lee, M. H., Kim, J., Kim, K. H., Kim, C. J. 2006. Amygdalin Induces Apoptosis through Regulation of Bax and Bcl-2 Expressions in Human DU145 and LNCaP Prostate Cancer Cells. Biological and Pharmaceutical Bulletin, vol. 29, no. 8, p. 1597-1602. https://doi.org/10.1248/bpb.29.1597 PMid:16880611
Chang, J., Zhang, Y. 2012. Catalytic degradation of amygdalin by extracellular enzymes from Aspergillus niger. Process Biochemistry, vol. 47, no. 2, p. 195-200. https://doi.org/10.1016/j.procbio.2011.10.030
Ihedioha, J. T., Okafor, C., Ihedioha, T. E. 2004. The haematological profile of the Sprague Dawley out bred albino rat in Nsukka. Animal Research International, vol. 1, no. 2, p. 125-132.
Jakubcova, Z., Zeman, L., Mares, P., Mlcek, J., Jurikova T., Dostalova, L., Mrazkova, E., Mrkvicova, E., Balla, S., Sochor, J. 2014. Effect of chamomile supplements to feeding doses on antimicrobial parameters in poultry. Potravinarstvo, vol. 8, no. 1, p. 228-232. https://doi.org/10.5219/383
Jiagang, D., Li, C., Wang, H., Hao, E., Du, Z., Bao, C., Jianzhen, L., Wang, Y. 2011. Amygdalin mediates relieved atherosclerosis in apolipoprotein E deficient mice through the induction of regulatory T cells. Biochemical and Biophysical Research Comunication, vol. 411, no. 3, p. 523-529. https://doi.org/10.1016/j.bbrc.2011.06.162 PMid:21756879
Kjeldahl, J. 1883. New method for the determination of nitrogen in organic substances. Zeitschrift für analytische Chemie, vol. 22, no. 1, p. 366-383. https://doi.org/10.1007/BF01338151
Kovacova, V., Omelka, R., Sarocka, A., Sranko, P., Adamkovicova, M., Toman, R., Halenar, M., Kolesarova, A., Martiniakova, M. 2016. Histological analysis of femoral bones in rabbits administered by amygdalin. Potravinarstvo, vol. 10, no. 1, p. 393-399. https://dx.doi.org/10.5219/625
Liu, L., Duan, J., Tang, Y.m Guo, J., Yang, N., Ma, H., Shi, X. 2012. Taoren-Honghua herb pair and its main components promoting blood circulation through influencing on hemorheology, plasma coagulation and platelet aggregation. Journal of Ethnopharmacology, vol. 139, no. 2, p. 381-387. https://doi.org/10.1016/j.jep.2011.11.016 PMid:22123200
Makarević, J., Rutz, J., Juengel, E., Kaulfuss, S., Reiter, M., Tsaur, I., Bartsch, G., Haferkamp, A., Blaheta, R. A. 2014. Amygdalin blocks bladder cancer cell growth in vitro by diminishing cyklin A and cdk2. PLoS ONE, vol. 9, no. 8, p. 1-9. https://doi.org/10.1371/journal.pone.0105590 PMid:25136960
Mbanasor, U. U., Anene, B. M., Chiniezie, A. B., Nnaji, T. O., Eze, J. I., Ezekwe, A. G. 2003. Haematology of normal trypanosome infected muturu cattle in South-Eastern Nigeria. Nigerian Journal of Animal Production, vol. 30, no. 2, p. 236-241. https://doi.org/10.4314/njap.v30i2.3300
Melillo, A. 2007. Rabbit clinical pathology. Journal of Exotic Pet Medicine, vol. 16, no. 3, p. 135-145. https://doi.org/10.1053/j.jepm.2007.06.002
Mendelová, A., Mendel, L., Czako, P., Mareček, J. 2016. Evaluation of carotenoids, polyphenols content and antioxidant aktivity in the sea buckthorn fruit juice. Potravinarstvo, vol. 10, no. 1, p. 59-64. https://doi.org/10.5219/551
Milazzo, S., Lejeune, S., Ernst, E. 2007. Laetrile for cancer: a systematic review of the clinical evidence. Support Care Cancer, vol. 15, no. 6, p. 583-595. https://doi.org/10.1007/s00520-006-0168-9 PMid:17106659
Moertel, C. G., Ames, M. M., Kovach, J. S., Moyer, T. P., Rubin, J. R., Tinker, J. H. 1981. A pharmacologic and toxicological study of amygdalin. JAMA, vol. 245, no. 6, p. 591-594. https://doi.org/10.1001/jama.1981.03310310033018 PMid:7005480
Nabavizadeh, F., Alizadeh, A. M., Sadroleslami, Z., Adeli, S. 2011. Gastroprotective effects of amygdalin on experimental gastric ulcer: Role of NO and TNF-α. Journal of Medical Plants Research, vol. 5, no. 14, p. 3122-3127.
Newton, G. W., Schmidt, E. S., Lewis, J. P., Conn, E., Lawrence, L. 1981. Amygdalin toxicity studies in rats predict chronic cyanide poisoning in humans. The western Journal of Medicine, vol. 134, no. 2, p. 97-103. PMid:7222669
Nwosu, C. C. 1979. Characteristics of local chicken of Nigeria and its potential for egg and meat production. In Poultry Production in Nigeria, 1st National Seminar on Poultry Production. Nigeria, Zaria.
Olafedehan, C. O., Obun, A. M., Yusuf, M. K., Adewumi, O. O. Olafedehan, A. O., Awofolaji, A. O., Adeniji, A. A. 2010. Effects of residual cyanide in processed cassava peel meals on haematological and biochemical indices of growing rabbits. In 35th Annual Conference of the Nigerian Society for Animal Production. Nigeria : University of Ibadan, p. 212.
Onyeyili, P. A., Egwu, G. O., Jibike, G. I., Pepple, O. J., Gbaegbulan, J. O. 1991. Seasonal variation in haematological indices in the grey breasted guinea fowl (Numida mealagris Gallata pallatas). Nigerian Journal of Animal Production, vol. 18, no. 2, p. 108-111.
Oyewole, O. I., Olayinka, E. T. 2009. Hydroxocobalamin (vit b12a) effectively reduced extent of cyanide poisoning arising from oral amygdalin ingestion in rats. Journal of Toxicology Environmental Health Science, vol. 1, no. 1, p. 8-11.
Perrez, J. J. 2013. Amygdalin analogs for the treatment of psoriasis. Future Medicinalk Chemistry, vol. 5, no. 7, p. 799-808. https://doi.org/10.4155/fmc.13.27 PMid:23651093
Rauws, A. G., Olling, M., Timmerman, A. 1982. The pharmacokinetics of amygdalin. Archive of Toxicology, vol. 49, no. 3, p. 311-312. https://doi.org/10.1007/BF00347879 PMid:7092570
Ryu, K. H., Han, H. Y., Lee, S. Y.,Jeon, S. D., Im, G. J., Lee, B. Y., Kim, K., Lim, K. M.,Chung, J. H., 2009. Ginkgo biloba extract enhances antiplatelet and antithrombotic effects of cilostazol without prolongation of bleeding time. Thrombosis Research, vol. 124, no. 3, p. 328-334. https://doi.org/10.1016/j.thromres.2009.02.010 PMid:19349067
Samy, R. P., Gopalakrishnakone, P. 2007. Current status of herbals and their future perspective. Nature Preceeding, vol. 7, no. 28, p. 1-13.
Schalm, O. W., Jain, N. C., Caroll, E. J. 1975. Veterinary haemtology. Philadelphia, USA : Lea and Fabiger. 368p. ISBN 9781437701739.
Soxhlet, F. 1879. Die gewichtsanalytische Bestimmung des Milchfettes. Dinglers Polytechnisches Journal, vol. 232, p. 461-465.
Suchard, J. R., Wallace, K. L., Gerkin, R. D. 1998. Acute cyanide toxicity caused by apricot kernel ingestion. Annals of emergency medicine, vol. 32, no. 6, p. 742-744. https://doi.org/10.1016/S0196-0644(98)70077-0
Togun, V. A., Oseni, B. S. A., Ogundipe, J. A., Arewa, T. R., Hammed, A. A., Ajonijebu, D. C., Oyeniran, A., Nwosisi, I. Mustapha, F. 2007. Effects of chronic lead administration on the haematological parameters of rabbit - a preliminary study. In 41st Conference af the Agriculture Society of Nigeria, Abeokuta, Ogun State, p. 341.
Tušimová, E., Kováčik, A., Halenár, M., Zbyňovská, K., Chrastinová, Ľ., Ondruška, Ľ., Jurčík, R., Kolesár, E., Kolesárová, A. 2016a. Energetic profile of rabbits after amygdalin administration. Journal of Microbiology, Biotechnology and Food Sciences, vol. 5, special no. 1, p. 50-52.
Tušimová, E., Kováčik, A., Halenár, M., Zbyňovská, K., Tomková, M., Tirpák, F., Chrastinová, Ľ., Ondruška, Ľ., Jurčík, R., Kolesár, E., Kolesárová, A. 2016b. Hepatic profile of female rabbits after amygdalin administration. In 12th International Scientific Conference Animal Physiolog. Bořetice : Mendel University in Brno, p. 253-259. ISBN 978-80-7509-416-2.
US EPA (US Environmental Protection Agency), 2010. Toxicological review of hydrogen cyanide and cyanide salts (CAS No. various) in support of summary information on the Integrated Risk Information System (IRIS). Washington, DC, USA : Environmental Protection Agency.
Vetter. V. 2000. Plant cyanogenic glycosides. Review. Toxicon: Oficial Journal of the International Society on Toxinology, vol 38, no. 1, p. 11-36. https://doi.org/10.1016/S0041-0101(99)00128-2
Vrzgula, L. 1990. Poruchy látkového metabolizmu hospodárskych zvierat a ich prevencia (Animal metabolism disorders and their prevention). Bratislava, Slovakia : Príroda. 503 p. ISBN 80-07-00256-1.
Yan, J., Tong, S., Li, J., Lou, J. 2006. Preparative Isolation and Purification of Amygdalin from Prunusarmeniaca L. with High Recovery by High-Speed Countercurrent Chromatography. Journal of Liquid Chromatography & Related Technologies, vol. 29, no. 9, p. 1271-1279. https://doi.org/10.1080/10826070600598985
Yildirim, F. A., Askin, M. A. 2010.Variability of amygdalin content in seeds of sweet or bitter apricot cultivars in Turkey. African Journal of Biotechnology, vol. 9, no. 39, p. 6522-6524.
Zhou, C. G., Qian, L., Ma, H., Yu, X., Zhang, Y., Qu, W., Zhang, X., Xia, W. 2012. Enhancement of amygdalin activated with β-D-glucosidase on HepG2 cells proliferation and apoptosis. Carbohydrate Polymers, vol. 90, no. 1, p. 516-523. https://doi.org/10.1016/j.carbpol.2012.05.073 PMid:24751072
- Authors retain copyright and grant the journal right of first publication with the work simultaneously licensed under a Creative Commons Attribution License that allows others to share the work with an acknowledgement of the work's authorship and initial publication in this journal.
- Authors are able to enter into separate, additional contractual arrangements for the non-exclusive distribution of the journal's published version of the work (e.g., post it to an institutional repository or publish it in a book), with an acknowledgement of its initial publication in this journal.
- Authors are permitted and encouraged to post their work online (e.g., in institutional repositories or on their website) prior to and during the submission process, as it can lead to productive exchanges, as well as earlier and greater citation of published work (See The Effect of Open Access).
