Skip to main content Accessibility help

Bee (Apis mellifera) Venom Produced Toxic Effects of Higher Amplitude in Rat Thoracic Aorta than in Skeletal Muscle—An Ultrastructural Study

  • Adrian Florea (a1) and Constantin Crăciun (a2)


In this study, changes produced in aorta and triceps surae muscle of Wistar rats as response to bee venom (BV) envenomation were analyzed by transmission electron microscopy and morphometry. A subchronic treatment of 30 days with daily doses of 700 μg BV/kg and an acute-lethal treatment with a single dose of 62 mg BV/kg were performed. The subchronic treatment resulted in endothelial cell retraction, a thicker subendothelial layer, and thinner elastic laminae and musculoelastic layers in aorta, and thicker endothelium and basal laminae in skeletal muscle. In both tissues polymorphous, swollen mitochondria with disrupted cristae were observed. The acute treatment produced extensive endothelial lesions, breakdown of the collagen layer and migration of muscle cells toward the intima in the aorta, and dilatation of endoplasmic reticulum in the skeletal muscle cells. Mitochondria were almost devoid of cristae or with few circular cristae in the smooth muscle cells while most of the mitochondria presented abnormal circular cristae in the skeletal muscle cells. Degenerative alterations in the aorta were of higher intensity in our experiments—both the intima and media strongly responded to BV, in contrast to those found at the level of the skeletal muscle cells where a moderate degenerative myopathy was recorded.


Corresponding author

Corresponding author. E-mail:


Hide All
Adam, S.K., Das, S. & Jaarin, K. (2009). A detailed microscopic study of the changes in the aorta of experimental model of postmenopausal rats fed with repeatedly heated palm oil. Int J Exp Pathol 90, 321327.
Allaire, E. & Clowes, A.W. (1997). Endothelial cell injury in cardiovascular surgery: The intimal hyperplastic response. Ann Thorac Surg 63, 582591.
Arroyo, O., Rosso, J.P., Vargas, O., Gutiérrez, J.M. & Cerdas, L. (1987). Skeletal muscle necrosis induced by a phospholipase A2 isolated from the venom of the coral snake Micrurus nigrocinctus nigrocinctus. Comp Biochem Physiol B 87, 949952.
Azevedo-Marques, M.M., Cupo, P., Hering, S.E., Costa, R. & Ferreira, D.B. (2001). Clinical-laboratory and therapeutic aspects of envenomation caused by africanized bees. J Venom Anim Toxins 5, 154171.
Betten, D.P., Richardson, W.H., Tong, T.C. & Clark, R.F. (2006). Massive honey bee envenomation-induced rhabdomyolysis in an adolescent. Pediatrics 117, 231235.
Budin, S.B., Othman, F., Louis, S.R., Abu Bakar, M., Radzi, M., Osman, K., Das, S. & Mohamed, J. (2009). Effect of alpha lipoic acid on oxidative stress and vascular wall of diabetic rats. Rom J Morphol Embryol 50, 2330.
Cliff, W.J. (1970). The aortic tunica media in aging rats. Exp Mol Pathol 13, 172189.
Congiu, T., Schembri, L., Tozzi, M., Guasti, L., Maio, R.C., Cosentino, M. & Marino, F. (2010). Scanning electron microscopy examination of endothelium morphology in human carotid plaques. Micron 41, 532536.
Connat, J.L., Busseuil, D., Gambert, S., Ody, M., Tébaldini, M., Gamboni, S., Faivre, B., Quiquerez, A.L., Millet, M., Michaut, P. & Rochette, L. (2001). Modification of the rat aortic wall during ageing; possible relation with decrease of peptidergic innervation. Anat Embryol 204, 455468.
Dawson, C.R. (1978). The interaction of bee melittin with lipid bilayer membranes. Biochim Biophys Acta 510, 7586.
Dejana, E., Corada, M. & Lampugnani, M.G. (1995). Endothelial cell-to-cell junctions. FASEB J 9, 910918.
Dempsey, C.E. (1990). The action of melittin on membranes. Biochim Biophys Acta 1031, 143161.
Ejerblad, S. & Ericsson, J.L. (1979). Ultrastructure of the aorta in experimental uraemia. Acta Chir Scand 145, 331343.
Fitzgerald, K.T. & Flood, A.A. (2006). Hymenoptera stings. Clin Tech Small Anim Pract 21, 194204.
Florea, A. (2004). Veninul de Albine—Compus Complex cu Multiple Efecte. Bucharest, Romania: Apimondia.
Florea, A. & Crăciun, C. (2011). Abnormal mitochondrial cristae were experimentally generated by high doses of Apis mellifera venom in the rat adrenal cortex. Micron 42, 434442.
Florea, A., Crăciun, C., Puică, C., Gherghel, P. & Oprea, M.C. (2003a). Hepatotoxicitatea veninului de albine. Studiu histologic şi ultrastructural. Studia Univ Babeş-Bolyai Biol 48, 4966.
Florea, A., Oprea, M.C., Puică, C., Gherghel, P. & Crăciun, C. (2003b). Efecte structurale şi ultrastructurale determinate de veninul de albine în miocard. Studia Univ Babeş-Bolyai Biol 48, 89101.
Florea, A., Puică, C. & Crăciun, C. (2009). Reactions of rat hypothalamus to very high doses of bee venom, an histologic and ultrastructural study. Ann Rom Soc Cell Biol 14, 109117.
Florea, A., Puică, C., Crăciun, C., Gherghel, P. & Oprea, M.C. (2002). Modificări histologice şi ultrastructurale induse experimental la nivelul rinichiului prin administrarea veninului de albine în diferite doze. Ann Soc Nat Biol Cel 7, 327341.
Florea, A., Puică, C., Vințan, M., Benga, I. & Crăciun, C. (2011). Electrophysiological and structural aspects in the frontal cortex after the bee (Apis mellifera) venom experimental treatment. Cell Mol Neurobiol 31, 701714.
Forstermann, U., Mulsch, A., Bohme, E. & Busse, R. (1986). Stimulation of soluble guanylate cyclase by an acetylcholine-induced endothelium-derived factor from rabbit and canine arteries. Circ Res 58, 531538.
Forstermann, U. & Neufang, B. (1985). Endothelium-dependent vasodilation by melittin: Are lipoxygenase products involved? Am J Physiol 249, H14H19.
França, F.O.S., Benvenuti, L.A., Fan, H.W., Dos Santos, D.R., Hain, S.H., Picchi-Martins, F.R., Cardoso, J.L.C., Kamiguti, A.S., Theakston, R.D.G. & Warrell, D.A. (1994). Severe and fatal mass attacks by “killer” bees (Africanized honey bees—Apis mellifera scutellata) in Brazil: Clinicopathological studies with measurement of serum venom concentration. Q J Med 87, 269282.
Göktürk, C., Nilsson, J., Nordquist, J., Kristensson, M., Svensson, K., Söderberg, C., Israelson, M., Garpenstrand, H., Sjöquist, M., Oreland, L. & Forsberg-Nilsson, K. (2003). Overexpression of semicarbazide-sensitive amine oxidase in smooth muscle cells leads to an abnormal structure of the aortic elastic laminas. Am J Pathol 163, 19211928.
Guo, M., Breslin, J.W., Wu, M.H., Gottardi, C.J. & Yuan, S.Y. (2008). VE-cadherin and β-catenin binding dynamics during histamine-induced endothelial hyperpermeability. Am J Physiol Cell Physiol 294, C977C984.
Gupta, S.D., Gupta, S.K., Pal, D.K., Sarawagi, R. & Gupta, P. (2011). Microscopic study of aorta in relation of different age groups: An observational study. Int J Biol Med Res 2, 398403.
Gutiérrez, J.M., Núñez, J., Díaz, C., Cintra, A.C., Homsi-Brandeburgo, M.I. & Giglio, J.R. (1991). Skeletal muscle degeneration and regeneration after injection of bothropstoxin-II, a phospholipase A2 isolated from the venom of the snake Bothrops jararacussu. Exp Mol Pathol 55, 217229.
Gutiérrez, J.M. & Ownby, C.L. (2003). Skeletal muscle degeneration induced by venom phospholipases A2: Insights into the mechanisms of local and systemic myotoxicity. Toxicon 42, 915931.
Guyton, J.R., Lindsay, K.L. & Dao, D.T. (1983). Comparison of aortic intima and inner media in young adult versus aging rats. Am J Pathol 111, 234246.
Habermann, E. (1972). Bee and wasp venoms. The biochemistry and pharmacology of their peptides and enzymes are reviewed. Science 177, 314322.
Haschek, W.M., Rousseaux, C.G. & Wallig, M.A. (2009). Fundamentals of Toxicologic Pathology. Waltham, MA: Academic Press.
Hutcheson, I.R. & Griffith, T. M. (2000). Role of phospholipase A and myoendothelial gap junctions in melittin-induced arterial relaxation. Eur J Pharmacol 406, 239245.
Kjeldsen, K., Astrup, P. & Wanstrup, J. (1972). Ultrastructural intimal changes in the rabbit aorta after a moderate carbon monoxide exposure. Atherosclerosis 16, 6782.
Lee, W.R., Kim, S.J., Park, J.H., Kim, K.H., Chang, Y.C., Park, Y.Y., Lee, K.G., Han, S.M., Yeo, J.H., Pak, S.C. & Park, K.K. (2010). Bee venom reduces atherosclerotic lesion formation via anti-inflammatory mechanism. Am J Chin Med 38, 10771092.
LoVecchio, F., Cannon, R.D., Algier, J., Ruha, A.M., Curry, S.C., Wallace, K.L. & Graeme, K.A. (2007). Bee swarmings in children. Am J Emerg Med 25, 931933.
Lowenstein, C.J., Morrell, C.N. & Yamakuchi, M. (2005). Regulation of Weibel–Palade body exocytosis. Trends Cardiovasc Med 15, 302308.
Montecucco, C., Gutiérrez, J.M. & Lomonte, B. (2008). Cellular pathology induced by snake venom phospholipase A2 myotoxins and neurotoxins: Common aspects of their mechanisms of action. Cell Mol Life Sci 65, 28972912.
Ownby, C.L., Powell, J.R., Jiang, M.S. & Fletcher, J.E. (1997). Melittin and phospholipase A2 from bee (Apis mellifera) venom cause necrosis of murine skeletal muscle in vivo. Toxicon 35, 6780.
Pulido-Méndez, M., Rodriguez-Acosta, A. & Finol, H.J. (2002). Adrenal cortex ultrastructural alterations caused by zootoxins. Microsc Microanal 8, 926CD927CD.
Rapoport, R.M., Ashraf, M. & Murad, F. (1989). Effects of melittin on endothelium-dependent relaxation and cyclic GMP levels in rat aorta. Circ Res 64, 463473.
Rodríguez-Acosta, A., Peña, L., Finol, H.J. & Pulido-Méndez, M. (2004). Cellular and subcellular changes in muscle, neuromuscular junctions and nerves caused by bee (Apis mellifera) venom. J Submicrosc Cytol Pathol 36, 9196.
Schmidt, J.O. (1986). Allergy to hymenoptera venoms. In Venoms of the Hymenoptera. Biochemical, Pharmacological and Behavioural Aspects, Piek, T. (Ed.), pp. 509546. Orlando, FL: Academic Press.
Serrano, A.L. & Muñoz-Cánoves, P. (2010). Regulation and dysregulation of fibrosis in skeletal muscle. Exp Cell Res 316, 30503058.
Sitprijaa, V. & Suteparak, S. (2008). Animal toxins: An overview. Asian Biomed 2, 451457.
Son, D.J., Kang, J., Kim, T.J., Song, H.S., Sung, K.J., Yun do, Y. & Hong, J.T. (2007). Melittin, a major bioactive component of bee venom toxin, inhibits PDGF receptor beta-tyrosine phosphorylation and downstream intracellular signal transduction in rat aortic vascular smooth muscle cells. J Toxicol Environ Health A 70, 13501355.
Tanimura, A., Cho, T. & Tanaka, S. (1986). Aortic changes induced by hypercholesterolemia and hypercalcemia in rats. Exp Mol Pathol 44, 297306.
Valentin, E. & Lambeau, G. (2000). What can venom phospholipases A2 tell us about the functional diversity of mammalian secreted phospholipases A2? Biochimie 82, 815831.
Vetter, R.S. & Visscher, P.K. (1998). Bites and stings of medically important venomous arthropods. Int J Dermatol 37, 481496.
Vetter, R.S., Visscher, P.K. & Camazine, S. (1999). Mass envenomations by honey bees and wasps. West J Med 170, 223227.
Voss, J.C., Mahaney, J.E. & Thomas, D.D. (1995). Mechanism of Ca2+-ATPase inhibition by melittin in skeletal sarcoplasmic reticulum. Biochemistry 34, 930939.
Watt, I.M. (2003). The Principles and Practice of Electron Microscopy. Cambridge, UK: Cambridge University Press.
Woywodt, A., Streiber, F., De Groot, K., Regelsberger, H., Haller, H. & Aubitz, M. (2003). Circulating endothelial cells as markers for ANCA-associated small-vessel vasculitis. Lancet 361, 206210.
Yonamine, C.M., Costa, H., Silva, J.A.A., Muramoto, E., Rogero, J.R., Troncone, L.R.P. & Camillo, M.A.P. (2005). Biodistribution studies of bee venom and spider toxin using radiotracers. J Venom Anim Toxins Trop Dis 11, 3950.
Yoshizuka, M., Hara, K., Doi, Y., Mori, N., Yokoyama, M., Ono, E. & Fujimoto, S. (1992). The toxic effects of bis (tributyltin) oxide on the rat thoracic aorta. Histol Histopathol 7, 445449.


Bee (Apis mellifera) Venom Produced Toxic Effects of Higher Amplitude in Rat Thoracic Aorta than in Skeletal Muscle—An Ultrastructural Study

  • Adrian Florea (a1) and Constantin Crăciun (a2)


Full text views

Total number of HTML views: 0
Total number of PDF views: 0 *
Loading metrics...

Abstract views

Total abstract views: 0 *
Loading metrics...

* Views captured on Cambridge Core between <date>. This data will be updated every 24 hours.

Usage data cannot currently be displayed