Insect Physiology Insect venom (spider and scorpions) what is venom? spider venom? venom glands in spider composition of spider venom basic components of spider venom use in pharmaceuticals scorpion venom venom glands toxicity physiological effects of venom medical importance references

1. InsectVenom (spiders and
scorpios)
Course title: Insect Physiology

2. Venom
• A poisonous substance secreted by animals such as snakes, spiders, and
scorpions and typically injected into prey or aggressors by biting or stinging.
• It is delivered in a bite, sting, or similar action through a specially
evolved venom apparatus, such as fangs or a stinger, in a process
called envenomation.
• Venom is often distinguished from poison, which is a toxin that is passively
delivered by being ingested, inhaled, or absorbed through the skin
• Venomous animals cause tens of thousands of human deaths per year.
• Toxins from venom are used to treat a wide range of medical conditions
including thrombosis, arthritis, and some cancers.

3. • A branch of science, venomics, has been established to study the proteins
associated with venom and how individual components of venom can be used for
pharmaceutical means.
• These are chemicals of biological origin.
• Most venoms consist of a complex mixture of chemical substances, including
proteins, peptides, sugars and other substances that affect many systems of the
body.
• Common venom effects include paralysis, interference with blood clotting,
breakdown of muscle, pain, breakdown of tissues and effects on the
cardiorespiratory system.

4. Significance of venom
Use as a
bioweapon
To synthesize
insecticides
Its role in
medicine and
pharmaceuticals
To treat
envenomation

5. SpiderVenom
• The spiders are the largest group of
venomous animals, represented by more
than 38,000 species throughout the world.
Thirty spider species are known to be
harmful to humans.
• Human-spider encounters are frequent and
bites occasionally occur.
• A high number of biting events are observed
in human populations at high rates by
Phoneutria nigriventer because those spiders
infest clothing and shoes.
• Venom glands are present in most spiders,
but they are absent in the family Uloboridae

6. Venom glands of spiders
• The venom system of spiders is organized around the chelicerae, which
differ in organization according to the lineage:
• Mesothelae and Mygalomorphae possess chelicerae that are
orthognathous (chelae in parallel orientation)
• The araneomorphs evolved chelicerae that are labidognathous (chelicerae
are facing each other).

7. • In spiders, the chelicerae feature two functional units that move in a jack-
knife fashion.
• The first unit, a basal segment, is attached to the prosoma and forms a
mobile base for the second unit, a fang.
• Internally, the venom system of each chelicera consists of a venom gland
connected to a narrow opening at the fang tip via a thin venom duct
• Each venom gland is embedded in muscles and nerves, enabling fine control
of venom release
• Localization of venom glands differs between orthognathous and
labidognathous types. While the venom gland of the former is localized in
the basal segment of the chelicerae, it can extend into the prosoma in the
latter.
• Venom glands in spiders are further functionally compartmentalized and
their subsections produce and modify different venom components.

9. Composition of spider venom
• Spiders produce their venom components in specialized secretory cells in
the venom gland. The venom gland is surrounded by muscular layers
controlling venom release by squeezing the venom gland.
• Depending on the spider species, venom is released into the glandular
lumen by:
1. Disintegration of entire cells (holocrine secretion) or
2. By pinch off of parts of cells to form extracellular membrane-bound
vesicles and release of venom components from these vesicles (apocrine
secretion)

10. • In general, the spider venom of a given species is a mixture of over hundred
components acting on different targets including various receptors, mostly
located in the muscular or nervous system, cell membranes, and
extracellular matrix.
• Although single components may be toxic, it is the synergistic action
between the components, which deploys the full toxicity of the venom.
• The peptide and protein concentration of spider venom is often relatively
high with reports reaching from 65 µg/µL to 150 µg/µL .
• It is evident, that production of a fluid with these amounts of
peptides/proteins comes at high energetic costs for the spider.
• Some spiders economically use their venom by adaptation of the injected
amounts depending on prey size and movement or endangerment by the
prey

11. Basic components of spider venom
Spider venom components are typically divided into four
groups.
• (1) Small molecular mass compounds (SMMSs),
• (2) antimicrobial peptides (only a few spider families),
• (3) peptide neurotoxins
• (4) proteins and enzymes

12. Small Molecular Mass Compounds
• Small molecular mass compounds (SMMCs) are thought to be present in most
spider venoms. They include ions, organic acids, nucleotides, nucleosides, amino
acids, amines, and polyamines.
• Venom is rich in potassium and poor in sodium. These cation concentrations are
opposite to the hemolymph concentrations.
• The high potassium content of venom is described to induce depolarization of
excitable cell membranes, leading to paralysis of the prey, and to synergistically
enhance the activity of venom peptides.
• Spider venom has an acidic pH with pH values reported between 5.3 and 6.1. Main
contributors to this acidic environment are organic acids, primarily citric acid,
which is by far the most described organic acid present in spider venom.
• Many SMMCs effect neuronal or neuromuscular signal transduction. Nucleosides
(some with sulfate-ester) are known from many spider venoms and have been
reported to block kininate receptors and L-type Ca2+ channels.

13. Antimicrobial Peptides
• Antimicrobial peptides (AMPs) are also termed cytolytic or cationic
peptides.
• AMPs often feature high positive net charges and a high number of
hydrophobic amino acids.
• They are widely distributed as major components of animal immune
systems and are also present in various arthropod venoms, such as ant,
scorpion, bee, and wasp venoms.
• AMPs disrupt the integrity of cellular membranes.

14. Cytolytic activity

15. Cysteine-Rich Peptides
• Cysteine-rich peptides are the best investigated venom components and are
believed to exist in most spider venoms.
• Spider venoms typically contain dozens of different cysteine-rich peptides,
whereof most are thought to act on channels and receptors on membranes of
excitable cells.
• That is why they are often referred to as neurotoxic peptides or neurotoxin-like
peptides.

16. Structural Motifs
• The most prominent structural motif of spider venom cysteine-rich peptides
is the inhibitor cystine knot (ICK) motif.
• Inhibitory cystine knot (ICK) as part of the backbone of cysteine rich
peptides a motif that is formed by two disulfide bridges, and of the peptide
and a third disulfide bridge going through this loop.
• Moreover, these toxins can recognize an ion channel region far from the
pore, and they induce a shift of channel opening to more depolarized
potentials that alter the voltage dependent properties of K+, Na+ or
Ca++ currents.
• Thus, spider peptides are more gating modifiers than pore blockers

18. Sulphated nucleosides

19. Use in pharmaceuticals
• The thought of spiders may make your skin crawl, but a new study suggests
that maybe we should put our hatred of the eight-legged beasts to one side
• Spider venom has for a long time received only small attention due to its
limited impact on human health. Research only gained in focus after
realizing the huge pharmaceutical potential of spider venom peptides.
• Peptites of spider venom are target specific and have physiological stability

21. ScorpionVenom
• Scorpions are the most primitive arachnids that exist on the earth for 430
millions of years.
• They are the most venomous arthropods that belong to class Arachnida of
phylum Arthropoda.These animals are found in all continents except
Antarctica.
• Scorpions belonging to Buthidae family are more toxic and medically
important .They cause health problems in subtropical and tropical regions.
• Scorpion venom is the key to their success which ensures their survival by
defending themselves from preys, predators, and competitors

22. • Globally, there are 2231 various scorpion species, consist of 208 genera
representing in 20 families, from which 1500 scorpion species are venomous
and approximately 50 species are extremely harmful to humans.
• Scorpion envenomation is a significant problem for public health and causes
a wide range of clinical manifestations in sub-tropical and tropical
countries).
• Scorpion venom contains a wide variety of biomolecules which can disturb
physiological activity of the host on envenomation.

23. • Children and elderly patients have increased chance of complications due to
this problem.
• However, age, venom dosage, nutritional state, geographical area, and
season of the scorpion, as well as weight and age of the victim, individual
sensitivity, and site of sting are important parameters which affect the
severity of envenomation.
• Although, most scorpion stings cause death of humans if not treated
instantly.
• The treatment which is recommended for scorpion envenomation is therapy
with antivenom.
• Hyperimmune serum is obtained from animals such as horses, after
immunizations with the venom

24. Venom glands of scorpions
• The telson, situated at the end
of the metasoma, is a bulb-
shaped structure that contains
the venom glands and a sharp,
curved stinger to deliver
venom.
• The scorpion venom is used for
both prey capture and defense.
• It is a complex mixture of
neurotoxins and other
substances; each species has a
unique composition

25. Chemical composition of scorpion venom
• Scorpion venom contains a wide variety of compounds such as water,
mucosa, low molecular weight peptides, enzymes, free amino acids,
biogenic amines, nucleotides, mucopolysaccharides, mucoproteins,
histamine, serotonin, heterocyclic components, and several unidentified
substances.
• Scorpion venoms are highly complex mixtures of such molecules, and it is
estimated that 100,000 different components are present in the scorpion
venom around the world.
• Toxins are the thoroughly studied components of scorpion venom.This is
due to their pharmacological effect on ion channels and their clinical use as
neurotoxins

27. • Both disulfide and non-disulfide bridged peptides (NDBP) are present in the
scorpion venoms whereas NDBP are major components of it.
• low molecular weight peptides depict more than a third of all the peptides
that are determined in the scorpion venom.
• Such toxins are best known for their deleterious effects on organisms, but
paradoxically, they display antimalarial, antimicrobial, anticancer, and
immunosuppressing activities that are important for the development of
drugs

29. Novel alkoloids

30. Toxicity of scorpion venom
• Scorpion venom is highly toxic because it is composed of neurotoxin,
nephrotoxin, cardiotoxin, and hemolytic toxin which affect ion channels,
enzymes, and allergenic compounds.
• The toxicity of scorpion venom depends on their contents in neurotoxins.
• Low molecular weight peptides that interact with ion channels and causing
impairment of the proper functions of excitable cells in nerve and muscle
tissues which is usually responsible for the known symptoms of
envenoming.

31. • Scorpion toxins are classified into two main categories according to their
target site and size:
• short chain toxins which are composed of 30–40 amino acids and
constrained by 3 or 4 disulfide bridges that block the K+ channels
• long chain toxins which are composed of 60–75 amino acids and cross-linked
by 4 disulfide bridges that affect specifically Na+ channels.
• These toxins have been used as useful pharmacological probes to study the
ion channels because of their high affinity and specificity

33. Physiological effects of scorpion venom
• Physiological effects of scorpion sting vary widely from inflammation or local pain
to severe complications such as pulmonary edema, nervous disorder, and
cardiogenic shock.
• Scorpion toxins cause massive release of neurotransmitter such as catecholamines
which generates a cascade of events that can progress to heart failure, pulmonary
edema, arterial hypotension or hypertension, arrhythmia, tachycardia or
bradycardia, unconsciousness, and death.
• The cytotoxin from H. lepturus causes psychological problems (Mental disorders,
Anxiety, Depression, Schizophrenia, etc.) necrotic ulcers, cutaneous necrosis,
hemoglubinuria, renal failure, ankylosis of the joints, fatal hemolysis, hematuria
and even death.
• Scorpion venom is linked to dysfunctions of the immune system by recruiting
inflammatory cells, leukocytes, platelet activating factor, adhesion molecules,
immunoglobulins, and cytokines

35. Medical importance of scorpion venom
• Scorpion venom depict interesting compounds for the development of
novel drugs, for example, drugs for cancer, neurological disorders,
cardiovascular diseases, and analgesics.
• Scorpion venom has apoptogenic, cytotoxic, immunosuppressive, and
antiproliferative effects. Therefore, scorpion venom can be utilized against
various cancers like glioma, leukemia, human neuroblastoma, brain tumor,
melanoma, prostate cancer, and breast cancer.

36. Medical importance of spider venom
Scorpion toxins
for analgesic
Scorpion toxins
for epilepsy
Scorpion toxins
for malaria
Scorpion toxins
for cardiovascular
diseases
Scorpion toxins
for autoimmune
diseases
Scorpion venom
for treatment of
diabetes
Scorpion venom
and microbial
infections
Scorpion toxins
for cancer

37. Scorpion toxins for cardiovascular diseases

38. References
• Sannaningaiah, D., Subbaiah, G. K., & Kempaiah, K. (2014). Pharmacology
of spider venom toxins. Toxin Reviews, 33(4), 206-220.
• Peigneur, S., & Tytgat, J. (2018). Toxins in drug discovery and
pharmacology. Toxins, 10(3), 126.
• Schmidtberg, H., von Reumont, B. M., Lemke, S., Vilcinskas, A., & Lüddecke,
T. (2021). Morphological analysis reveals a compartmentalized duct in the
venom apparatus of the wasp spider (Argiope bruennichi). Toxins, 13(4), 270.
• Langenegger, N., Nentwig, W., & Kuhn-Nentwig, L. (2019). Spider venom:
components, modes of action, and novel strategies in transcriptomic and
proteomic analyses. Toxins, 11(10), 611.

39. • Ortiz, E., Gurrola, G. B., Schwartz, E. F., & Possani, L. D. (2015). Scorpion
venom components as potential candidates for drug
development. Toxicon, 93, 125-135.
• Ghosh, A., Roy, R., Nandi, M., & Mukhopadhyay, A. (2019). Scorpion venom–
toxins that aid in drug development: a review. International journal of
peptide research and therapeutics, 25(1), 27-37.
• Tobassum, S., Tahir, H. M., Arshad, M., Zahid, M. T., Ali, S., & Ahsan, M. M.
(2020). Nature and applications of scorpion venom: an overview. Toxin
Reviews, 39(3), 214-225.