See discussions, stats, and author profiles for this publication at: https://www.researchgate.

net/publication/228625069

Animal toxins: An overview

Article  in  Asian biomedicine · December 2008

CITATIONS READS
4 2,278

2 authors, including:

Visith Sitprija

300 PUBLICATIONS   3,997 CITATIONS   

SEE PROFILE

All content following this page was uploaded by Visith Sitprija on 13 March 2014.

The user has requested enhancement of the downloaded file.

Asian Biomedicine Vol. 2 No. 6 December 2008;451-457

Review article

Animal toxins: an overview

Visith Sitprijaa, Suchai Suteparakb

a
Queen Saovabha Memorial Institute, The Thai Red Cross Society, Bangkok 10330,
b
Department of Medicine, Faculty of Medicine, Chulalongkorn University, Bangkok 10330, Thailand

Toxins in the environment, derived from animals, water and food, are a worldwide problem but much more
prevalent in tropical and less developed regions. There, they also present a greater potential hazard to humans.
We present a brief review of what has been the subject of classical and more recent studies from the Southeast
Asia region.

Keywords: Animal toxins, cell injury, hemodynamics, membrane.

Animal toxins are a complex mixture of
polypeptides, enzymes and chemicals which can cause
cellular injury. Several mechanisms are involved in
pathophysiology of venom poisoning. Direct injury can
be induced by chemicals, enzymes and polypeptides.
Polypeptides exert their effect through action on
ion channels and receptors on the cell membrane.
The action of polypeptides upon ion channels and
receptor sites of excitable membranes through
signal transduction causes the release of
neurotransmitters which results in neuromuscular
effects. Enzymes can cause membrane lysis, pore
formation, cytoskeletal destruction, release
inflammatory and vasoactive mediators with action
on the coagulation pathway at various levels.
Proteolytic enzymes and phospholipase A 2 are
important causes of cellular injury and coagulopathy.
Indirectly, animal enzymes, especially phospholipase
A2 and metalloproteases, can induce the release of
vasoactive mediators and proinflammatory cytokines
which can lead to hemodynamic alterations and cause
organ injury. Cardiovascular symptoms are therefore
common. They can also trigger the inflammatory
process with generation of adhesion molecules,
complement activation, acute phase proteins, free
radicals, increased vascular permeability and increased
blood viscosity. Local reactions include pain, swelling
and redness. Hemodynamic changes may result if
Correspondence to: Professor Visith Sitprija, Queen Saovabha
Memorial Institute, The Thai Red Cross Society, 1871 Rama IV
Rd., Bangkok 10330, Thailand. E-mail: visithstprj@yahoo.com
the process is severe. Immunologic reaction usually
manifests in the form of allergic response such as
skin rashes and edema. In the severe form,
anaphylaxis with respiratory and cardiovascular
symptoms may occur.
Ion transport and neurotransmitters
Several animal toxins act on ion channels causing
either polarization or depolarization of excitable
membranes which affects the action potential and
neuromuscular function [1]. Intracellular calcium
regulated by Ca channels controls neurotransmitter
secretion and release. Opening of Ca channels by
depolarization or ligand stimulation increases
intracellular Ca and releases neurotransmitters.
On the contrary, closing of Ca channels by toxins or
hyperpolarization decreases neurotransmitter
secretion. Activation of Na channels and closing of K
and chloride channels cause depolarization. Opening
of K and chloride channels and closing of Na channels
result in hyperpolarization. A number of marine animal
toxins, arthropod toxins and some snake venoms cause
neuromuscular symptoms through effects on ion
channels [2-5]. Several toxins act on Na channels at
different sites [6]. Site 1 binds tetrodotoxin, saxitoxin
and μ conotoxin blocking channel conductance. Site
2 binds lipophilic toxins such as batrachotoxin opening
the channel. Sea anemone toxins and alpha scorpion
toxins bind site 3 and slow down inactivation. βeta
scorpion toxins bind site 4 and activate the channel.
In some epithelial cells, increased intracellular Ca
enhances enzyme or hormone secretion. Inhibition of
452 V. Sitprija, S. Suteparak

some transport mechanism can result in serum
electrolyte changes. Hyperkalemia and hyponatremia
in toad and coelenterate venom poisoning are the result
of inhibition of Na-K-ATPase [7-9] with Na influx
and K outflux. Some toxins form pores on the
membrane resulting in influx and outflux of ions
[10, 11]. Na influx predominates causing swelling
of the cells. Massive Ca influx can cause cell death.
Table 1 shows effects of animal toxins on cell
membranes through action of ion channels and pore
formation.
Several snake venoms block nicotinic
acetylcholine receptors at the neuromuscular junction
resulting in muscular weakness and paralysis. The
action is post-synaptic. Muscarinic toxins from mamba
snakes inhibit the binding of quinuclidinyl benzilate
to muscarinic acetylcholine receptors. Mamba
fasciculins inhibit acetylcholinesterase, thus enhancing
the action of acetylcholine [3, 12]. Some venoms
have pre-synaptic action through inhibition of
neurotransmitter release from the nerve ending. Other
receptors for neurotransmission are catecholamine,
serotonin, glutamate, opioid, NO, and γ-aminobutyric
acid (GABA) receptors. Neurotransmission can be
affected by animal toxins through effects on ion
channels and receptors.

Table 1. Animal toxin effects on ion channels and pore formation

Na channel K channel Ca channel Cl channel Pore formation

Jellyfish +

Sea anemone +

μ conotoxin

δ conotoxin

ω conotoxin

Ciguatoxin

Tetrodotoxin

Saxitoxin

Gonyautoxin

Palytoxin +

Maitotoxin

Stonustoxin

Annelid

Brevetoxin

Spider

Scorpion +

Bratachotoxin

Dendrotoxin

Bee +

* = activation or slow inactivation; = inactivation

Vol. 2 No. 6
Animal toxins
December 2008
Enzymes and inflammatory mediators
Cellular injury can be induced by enzymes
especially phospholipase A2 (PLA2) and proteases on
the cell membrane. Phospholipases A2 are enzymes
that catalyze the hydrolysis of the 2-acylester bond
of phosphoglycerides. Extracellular forms of PLA2
are abundant in the secretions of exocrine glands
such as pancreas and venom glands as well as at
inflammatory sites. Phospholipases A2 are categorized
into three classes (13). Class I consists of PLA2 from
the mammalian pancreas and from elapid and
hydrophid venoms. Class II comprises mammalian
PLA2 from inflammatory sites or secreted by blood
platelets and from viperid and crotalid venoms. Class
III includes PLA2 (Ca dependent) from venoms of
bees (Apis mellifera) and Gila monster (Heloderma)
with preference for phosphatidyl glycerol. Cellular
injury caused by PLA 2 results in hemolysis,
rhabdomyolysis, endothelial necrosis, renal tubular, and
neuronal damage. PLA2 and proteases can cause a
cascade effect at various levels of blood coagulation
causing bleeding diathesis. Metalloproteases can
cause cytoskeleton destruction, disrupting cellular
adhesion, cell damage and apoptosis [14, 15]. Habu
snake venom has a direct effect on the mesangial
cells and vascular endothelial cells. Continuous
incubation of these cells with the venom decreases
cell viability and increases the number of apoptotic
cells [16, 17]. In the Madin-Darby canine kidney
(MDCK) cell culture, Bothrops moojeni crude venom
decreases transepithelial electrical resistance across
the cellular monolayers, decreases neutral red uptake
of vero cells, causes disarray of the cytoskeleton, and
impairs cell to matrix adhesion (18). Cytotoxic
proteins and peptides of equinatoxin, palytoxin, melittin,
scorpion and jellyfish venoms can cause cellular
injury by pore formation on the cell membrane [10,
11, 19-21]. A number of proinflammatory cytokines
and mediators are released in toxin poisoning by
enzymes. PLA2 stimulates hypothalamus pituitary
axis to increase adrenocorticotrophic hormone,
corticosteroid, arginine vasopressin and acute phase
response [22]. Histamine, kinins, eicosanoids, platelet
activating factor, catecholamines and endothelins
are released. PLA2 is considered as a starter in the
formation of prostaglandins [23]. Zinc metalloprotease
cleaves gluthathione-D-transferase-tumor necrosis
factor-alpha-fusion protein (GST-TNFα) to generate
biologically active TNFα [24]. Elevations of serum
TNFα, IL-1, IL-6, IL-10, IFN-γ and NO are observed
453
in snake envenomation [25, 26]. Vasoactive mediators
including catecholamines, dopamine, thromboxanes,
angiotensin II, endothelins and prostaglandins are
released [27]. Involvement of cytokines and vasoactive
mediators in snake envenoming is therefore similar to
that observed in sepsis. Other inflammatory mediators
include complements, free radicals and adhesion
molecules. Spider and scorpion venoms also cause
elevation of serum proinflammatory cytokines and
mediators [28, 29]. Although the data are not available,
other envenomations with toxin enzymes are deemed
to cause the release of inflammatory cytokines and
mediators in a similar fashion.
Hemodynamic alterations
Hemodynamic alterations can be induced by either
toxins or endogenous vasoactive mediators from the
host. Sarafotoxin from burrow or mole vipers has
direct vascular effects similar to endothelin. Bothrops
jararaca venom inhibits angiotensin converting enzyme
and decreases blood pressure. Angiotensin II-like
peptide, kinins and vasoactive intestinal peptide
in amphibian skin can affect vascular resistance
and blood flow [30, 31]. Transient changes in
hemodynamics can be due to neurotransmitters such
as catecholamines or acetylcholine released from the
host. Catecholamine, thromboxane A2, serotonin and
histamine can cause pulmonary arterial constriction
and hypotension. Hypotension can be observed, and
transient hypertension can occur in jellyfish sting,
spider bite, scorpion sting and snake bite. In most
instances, hemodynamic changes are caused by
proinflammatory cytokines and vasoactive mediators
which can be severe with changes in cardiac output,
systemic and renal vascular resistance [32, 33].
Hemodynamic changes characterized by decreased
systemic vascular resistance and increased renal
vascular resistance parallel those observed in sepsis
involving similar proinflammatory cytokines and
vasoactive mediators. The renal blood flow and
glomerular filtration rate are decreased. Hypotension
is common in severe poisoning. Hemodynamic
alterations are therefore observed in poisoning by
toxins that are rich in enzymes such as snake and bee
or wasp venoms. Both protease and phospholipase
A2 can cause hemodynamics changes with decreased
renal blood flow [34]. Intravascular hemolysis,
hemorrhage, disseminated intravascular coagulation,
myonecrosis, complement activation and free radicals
further contribute to hemodynamic changes.
454 V. Sitprija, S. Suteparak
General clinical manifestations
Several natural toxins act on ion channels.
Neuromuscular symptoms are meant to paralyse the
prey for predation and for protection. In most natural
toxin envenoming, especially from the invertebrates,
neuromuscular symptoms including numbness,
cramps, ataxia and paralysis are common.
Besides the local reactions which consist of pain,
swelling, erythema, vesiculation and necrosis, systemic
reactions induced by cytokines and vasoactive
mediators can be observed. Cardiovascular symptoms
are frequently seen not only from the vasoactive
mediators but also from the specific effect of the
venom itself and of certain venoms which induce
rapidly increased cytosolic Ca such as box jellyfish
venom. Venoms as enzymes, in addition to causing
cellular injury, can exert effects on the coagulation
cascade causing bleeding diathesis. With inflammatory
reactions, hemodynamic changes and hematologic
perturbation, specific organ injury can occur. Renal
involvement is common. Immunologic reaction
revealed by anaphylaxis or hypersensitivity is another
clinical manifestation. Figure 1 shows pathophysiology
of animal toxin poisoning. Snake venom with large
quantity and several toxin components can produce
greater morbidity than other animal venoms.
Neuromuscular involvement
Through the actions on ion channels, neuro-
muscular receptors and inhibition of membrane
Figure 1. Pathophysiology of animal toxin poisoning and envenoming
ATPase neuromuscular symptoms are common in
animal toxin poisoning. Neuromuscular manifestations
include dizziness, fainting, numbness, blurred vision,
muscle cramps, ataxia, paralysis, muscular pain,
hypersalivation, nausea, vomiting and priapism [2-5].
Most marine toxins acting on ion channels cause
neuromuscular symptoms. Scorpion sting, spider
bite, bee and wasp stings and snake bite cause
neuromuscular symptoms through both action on ion
channels and muscle cell membrane by PLA2 causing
rhabdomyolysis.
Hematological involvement
Erythrocyte membrane injury induced by PLA2 can
cause intravascular hemolysis. Pore information on
the membrane and inhibition of Na-K ATPase can
cause cell swelling further contributing to hemolysis.
Intravascular hemolysis is commonly observed in snake
and arthropod envenomings. Some coelenterate toxins
can also cause hemolysis.
Snake venom enzymes, through their effects on
the blood coagulation cascade, platelets and vascular
endothelium, result in hemorrhagic diathesis and
disseminated intravascular coagulation. Bee stings and
spider bite can also cause disseminated intravascular
coagulation [35-38].
Pulmonary involvement
Pulmonary involvements in animal toxin
envenoming are manifested in several forms.
Vol. 2 No. 6
Animal toxins
December 2008
Respiratory paralysis can occur as the result of
neurotoxins acting on acetylcholine receptors or ion
channels either through activation or inactivation. The
effect on muscle of respiration can cause respiratory
failure. Marine toxins from coelenterates, sea urchin,
cone snail, certain fish, and several snake neurotoxins
can cause respiratory paralysis. The second form of
pulmonary involvement is pulmonary edema
secondary to hemodynamic changes and increased
vascular permeability induced by cytokines and
inflammatory mediators. This has been observed
in box jellyfish sting, scorpion sting and bee or wasp
sting [39-41]. The third form is pulmonary hemorrhage
due to pulmonary capillary injury caused by
metalloproteases and coagulopathy. Envenomation by
viperid or crotalid snakes is an important cause of
pulmonary hemorrhage which can be life threatening.
Finally, pulmonary hypertension causing syncope can
be due to catecholamine, thromboxane A2, serotonin
and histamine.
Gastrointestinal involvement
Nausea, vomiting and diarrhea are common in
marine toxin envenomation. Hepatitis with jaundice
has been described following Hymenoptera, scorpion
and spider envenomation [36, 39, 42-44]. Multiple
stings by bees, wasps and hornets can cause severe
hepatocellular injury. Pancreatitis can occur following
wasp and bee stings.
Renal involvement
As a highly vascularized and excretory organ,
the kidney is vulnerable to toxin poisoning. Release
of proinflammatory cytokines and vasoactive
mediators by toxins leading to decreased renal
blood flow is fundamental in the development of
nephropathy [45]. Renal injury can also be induced
by toxin enzymes especially phospholipases
and metalloproteases. Other factors associated
with inflammation from cellular injury including
hemorrhage, hypovolemia, intravascular coagulation,
intravascular hemolysis, rhabdomyolysis, complements
and free radicals are additional and important insults
for the kidney injury. The severity of inflammatory
reaction is critical for the development of renal injury.
In this respect, a large amount of toxin inducing a
great degree of enzymatic and inflammatory reaction
is likely to cause renal damage. Snake bite and
multiple insect stings are therefore common causes
of renal injury, and tubular necrosis is an important
455
pathological change leading to acute renal failure.
Glomerulonephritis, vasculitis and interstitial nephritis
in animal toxin poisoning are less common, but have
been reported in viper bite and insect stings, and have
been attributed to the direct toxicity of the venoms.
Hypersensitivity to venoms can play some role in
interstitial nephritis. Nephrotic syndrome has been
described in snake bite and insect stings.
Hyperkalemia, acidosis and bradycardia have been
reported following ingestion of aphrodisiac pills
containing toad venom with large quantities of cardiac
glycosides that inhibit Na-K ATPase [7, 8]. A number
of toxins exert effects on ion transport in the renal
tubules. Melittin from bee venom inhibits Na and
phosphate reabsorption but increases Ca reabsorption
in proximal tubules [46]. The venom from the green
mamba snake decreases Na resorption in the distal
nephron [47]. Charybdotoxin and iberiotoxin from
scorpions (Leiurus quinquestriatus hebraeus and
Buthus tamulus) close Ca-activated K channels [3].
In the kidney, these channels are flow dependent for
K excretion in the distal nephron [48]. The relevance
of these toxins in the clinical renal setting is not
understood.
Poisoning and envenoming by animal toxins are
of among the important problems in the tropics. Except
for snake bites, the data are usually underestimated
due to the lack of records. During the past few decades
much progress has been made in the physiology,
pharmacology and biochemistry of toxins. Toxins are
used as tools for probing biochemical pathways and
mechanisms. Toxin research toward new drug
discovery is exciting and challenging.
References
1. Catterall WA, Cestele S, Yarov-Yarovoy V, Yu FH,
Konoki K, Scheuer T. Voltage-gated ion channels and
gating modifier toxins. Toxicon. 2007;49:124-41.
2. Fletcher JE, Jiang MS. Possible mechanism of action
of cobra snake venom cardiotoxin and bee venom
melittin. Toxicon 1993;31:669-95.
3. Harvey AL, Rowan EG, Vatanpour H, Fatehi M,
Castaneda O, Karlsson E. Potassium channel toxins
and transmitter release. Ann NY Acad Sci. 1994;710:
1-10.
4. Hung YM, Hung SY, Chou KJ, Huang NC, Tung CN,
Hwang DF, et al. Persistent bradycardia caused by
ciguatoxin poisoning after barracuda fish eggs
ingestion in southern Taiwan. Am J Trop Med Hyg.
2005;73:1026-27.
456 V. Sitprija, S. Suteparak
5. Newcomb R, Gaur S, Bell JR, Cruz L. Structural and
biosynthetic properties of peptides in cone snail
venoms. Peptides. 1995;16:1007-17.
6. Gray WR, Olivera BM, Cruz LJ. Peptide toxins from
venomous Conus snails. Ann. Rev Biochem. 1988;57:
665-700.
7. Brubacher JR, Lachmanen D, Ravikumar PR, Hoffman
RS. Efficacy of diagoxin specific Fab fragments
(Digibind) in the treatment of toad venom poisoning.
Toxicon. 1999;37:931-42.
8. Gowda RM, Cohen RA, Khan IA. Toad venom
poisoning: resemblance to digoxin toxicity and
therapeutic implications. Heart. 2003;89:e14.
9. Habermann E. Palytoxin acts through Na+, K+-ATPase.
Toxicon. 1989; 27:1171-87.
10. Brinkman D, Burnell J. Identification, cloning and
sequencing of two major venom proteins from box
jellyfish, Chironex fleckeri. Toxicon. 2007;50: 850-60.
11. Honma T, Minagawa S, Nagai H, Ishida M, Nagashima
Y, Shiomi K. Novel peptide toxins from acrorhagi,
aggressive organs of the sea anemone Actinia equina.
Toxicon 2005;46:768-74.
12. Karlsson E. Chemistry of protein toxins in snake
venoms. In: Snake Venoms, Handbook of Experimental
Pharmacology. Vol. 52, Lee CY (ed), Berlin:Springer
Verlag, 1979, p. 159-212.
13. Bon C, Choumet V, Delot E, Faure G, Robbe-Vincent A,
Saliou B. Different evolution of phospholipase A2
neurotoxins (B-neurotoxins) from Elapidae and
Viperidae snakes. Ann NY Acad Sci. 1994;710:142-8.
14. Fernandes CM, Zamuner SR, Zullani JP, Rucavado
A, Gutierrez JM, Teixeira Cde F. Inflammatory effects
of Ba P1 a metalloproteaes isolated from Bothrops
asper snake venom: leukocyte recruitment and release
of cytokines. Toxicon. 2006;47:549-59.
15. Kamaguti AS, Hay CRM, Theakston RDG, Zuzel M.
Insights into the mechanism of hemorrhage caused
by snake venom metalloproteinases. Toxicon 1996;
34:627-42.
16. Kubo A, Iwano M, Kobayahsi Y, Kyoda Y, Isumi Y,
Maruyama N et al. In vitro effects of Habu snake
venom on cultured mesangial cells. Nephron. 2002;
92:665-72.
17. Matsumoto K, Hiraiwa N, Yoshiki A, Ohnishi M,
Kusakabe M, et al. Tenascin-C expression and
splice variant in Habu snake venom-induced
glomerulonephritis. Exp Mol Pathol. 2002;72:186-95.
18. Boer-Lima PA, JA Gontijo, MA Cruz-Hofling. Bothrops
moojeni snake venom-induced renal glomeruli changes
in rats. Am J Trop Med Hyg. 2002;67:217-22.
19. Cajal Y, Jain MK. Synergism between mellitin and
phospholipase A 2 from bee venom: Apparent
activation by intervesicle exchange of phospholipids.
Biochemistry. 1997;36:3882-93.
20. Elgar D, Verdonek F, Grobler A, Fourie C, du Plessis J.
Ion selectivity of scorpion toxin-induced pores in
cardiac myocytes. Peptides 2006; 27: 55-61
21. Mebs D, Hucho F. Toxins acting on ion channels and
synapses. In: Handbook of Toxinology, Shier T,
Mebs D (eds), New York:Marcel Dekker, 1990,
p. 493-600.
22. Chisari A, Spinedi E, Voirol MJ, Giovambattista A,
Gaillard RC. A phospholipase A2-related snake venom
(from Crotalus durissus terrificus) stimulates
neuroendocrine and immune function determination
of different sites of action. Endocrinol.1998;139:
617-25.
23. Huang HC. Effects of phospholipase A2 from Vipera
russelli snake venom on blood pressure, plasma
prostacyclin level and renin activity in rats. Toxicon.
1984;22:253-64.
24. Moura-da-silva AM, Laing GD, Paine MJ, Dennison
JM, Politi V, Crampton JM, et al. Processing of
pro-tumor necrosis factor-alpha by venom
metalloproteinases: a hypothesis explaining local
tissue damage following snake bite. Eur J Immunol.
1996;26:2000-5.
25. Avila-Aguero ML, Paris MM, Hu S., Peterson PK,
Guitierrez JM, Lomonte B et al. Snakebite Study Group.
Systemic cytokine response in children bitten by
snakes in Costa Rica. Pediatr Emerg Care. 2001;17:
425-9.
26. Petricevich VL, Teixeira CFP, Tambourgi DV, Gutierrez
JM. Increments in serum cytokines and nitric oxide
levels in mice injected with Bothrops asper and
Bothrops jararaca snake venoms. Toxicon. 2000;38:
1253-66.
27. Thamaree S, Sitprija V, Leepipatpaiboon S.
Mediators and renal hemodynamics in Russell’s Viper
envenomation. J Nat Toxins. 2000;9:43-8.
28. De Souza AL, Malaque CM, Sztajnbok J, CC Romano,
AJ Duarte, AC Seguro. Loxosceles venom-induced
cytokine activation, hemolysis, and acute kidney
injury. Toxicon. 2008;51:151-6.
29. Pessini AC, Santos DR, Arantes EC, Souza G EP.
Mediators involved in the febrile response induced
by Tityus serrulatus scorpion venom in rats. Toxicon.
2006;48:556-66.
30. Daly JW, Myers CW, Whittaker N. Further
classification of skin alkaloids from neotropical
 Vol. 2 No. 6
Animal toxins
December 2008
poison frogs (Dendrobatidae), with a general survey
of toxic/noxious substances in the amphibian. Toxicon.
1987;25:1023-95.
31. Erspamer V, Melchiorri P, Nakajima T, Yasuhara T,
Endean R. Amino acid composition and sequence
of crinia-angiotension, an angiotensin II–like
endecapeptide from the skin of the Australian frog
Crinia georgiana. Experientia. 1979;35:1132-3.
32. Monteiro HSA, Da Silva IMSC, Martins AMC,
Fonteles MC. Effects of Crotalus durissus terrificus
venom and crotoxin on the isolated rat kidney. Braz J
Med Biol Res. 2001;34:1347-52.
33. Tungthanathanich P, Chaiyabutr N, Sitprija V. Effect
of Russell’s viper (Vipera russelli siamensis) venom
on renal hemodynamics in dogs. Toxicon. 1986;24:
365-71.
34. De Sousa Alves R, Do Nascimento NRF, Barbosa PSF,
Kerntopf MR, Lessa LM, De Sousa CM, et al. Renal
effects and vascular reactivity induced by Tityus
serrulatus venom. Toxicon 2005;46:271-6.
35. Cowell AK, Cowell RL, Tyler RD, Nieves MA. Severe
systemic reactions to Hymenoptera stings in three
dogs. J Am Vet Med Assoc. 1991;198:1014-6.
36. Kolecki P. Delayed toxic reaction following massive
bee envenomation. Ann Emerg Med 1999;33:114-6.
37. Lee S, Lynch KR. Brown recluse spider (Loxosceles
reclusa) venom phospholipase D (PLD) generates
lysophosphatidic acid (LPA) Biochem J. 2005;391 (Pt2):
317-23.
38. Petrolanu G, Lin J, Helfrich U, Maleck W, Rufer R.
Phospholipase A2-induced coagulation abnormalities
after bee sting. Ann J Emerg Med. 2000;18: 22-7.
39. El Nasr MS, Abdel Rahman M, Shoukry NA, Ahmed
MK, Eid SM, Fawzi AF, et al. The effect of scorpion
View publication stats
457
envenomation on the different organs of albino mice.
J Egypt Soc Parasitol 1992;22:833-8.
40. Humblet Y, Sonnet J, Van Ypersele de Strihou C. Bee
stings and acute tubular necrosis. Nephron. 1982;31:
187-8.
41. Oliveira EC, Pedroso PMO, Meirelles AEWB, Caroline
AP, Aline SG, David D. Pathological findings in dogs
after multiple African bee stings. Toxicon. 2007;49:
1214-8.
42. Franca FOS, Benvenuti LA, Fan HW, Dos Santos DR,
Hain SH, Picchi-Martins FR, et al. Severe and fatal
mass attacks by “killer” bees (Africanized honey bees
Apis mellifera scutellata) in Brazil: clinicopathological
studies with measurement of serum venom
concentrations. QJ Med. 1994;87:269-82.
43. Watemberg N, Weizman Z, Shahak E, Aviram M,
Moar E. Fatal multiple organ failure following massive
hornet stings. J Toxicol Clin Toxicol. 1995;33:471-4.
44. Zambrano A, Gonzalez J, Callejas G. Severe loxoscelism
with lethal outcome. Report of one case. Rev Med
Chil. 2005;133:219-23.
45. Sitprija V. Snakebite nephropathy. Nephrology. 2006;
11:442-8.
46. Han HJ, Yoon BC, Oh YJ, Park SH, Lee JH, Mar WC.
The water-soluble fraction (<10 KD) of bee venom
(Apis mellifera) produces inhibitory effect on apical
transporters in renal proximal tubule cells. Kidney
Blood Press Res. 2002;25:375-83.
47. Lisy O, Jougasaki M, Heublein DM, Schirger JA,
Chen HH, Wennberg PW, et al. Renal actions of
synthetic Dendroaspis natriuretic peptide. Kidney Int.
1999;56:502-8.
48. Sansom SC, Welling PA. Two channels for one job.
Kidney Int. 2007;72:529-30.