Module 9: Organ-Specific Toxicity

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Questions and Answers

What is the effect of Phospolipase A2 in snake venom?

Local and systemic myotox, pain, damage to lymphatic vessels, oedema, neurotox, and hemolysis (correct)

Hemorrhage

ECM degradation

Cytotox, necrosis, and neurotox

The symptoms of evenomation include skin necrosis and paralysis of eye muscles.

True

What is the purpose of capturing snake venom?

To develop antivenom and to obtain qualitative and quantitative information about the toxins present.

TGN1412 is a medicine supposed for treatment of ___________ and rheumatoid arthritis.

B-cell lymphatic leukemia Signup and view all the answers

What is the class of the antibody TGN1412?

IgG4 Signup and view all the answers

Cytokine storm is a rare side effect of TGN1412.

False Signup and view all the answers

What is the structure of the CD28 superagonist antibody?

The CD28 superagonist antibody binds exclusively to the laterally exposed C”D loop of the Ig like domain. Signup and view all the answers

Match the following toxins with their effects:

Phospolipase A2 = Local and systemic myotox, pain, damage to lymphatic vessels, oedema, neurotox, and hemolysis Snake venom metalloproteinases (SVMP) = Hemorrhage, myonecrosis, extracellular matrix degradation, blistering, pain, oedema, cardiovascular shock, nephrotox, and coagulopathy Three finger toxins = Cytotox, necrosis, and neurotox Dendrotoxin = Neurotox Signup and view all the answers

TGN1412 is a ___________ of CD28.

superagonist Signup and view all the answers

Snake venom can be used for the treatment of cancer.

True Signup and view all the answers

What is the main source of human exposure to aflatoxins?

Food consumption Signup and view all the answers

Aflatoxins are a type of genotoxin.

True Signup and view all the answers

What is the main mechanism of aflatoxin B1 leading to hepatocellular carcinoma (HCC)?

p53 mutations and inactivation, leading to proliferation and loss of growth control Signup and view all the answers

The compressor muscle in the 'cheek' of venomous snakes is responsible for the release of _______________ into the venom duct.

venom Signup and view all the answers

Match the following organ-specific toxins with their effects:

Aflatoxins = Hepatocellular carcinoma (HCC) Snake venom = Tissue damage and inflammation Coumarin derivatives = Blood clotting disorders Polycyclic compounds = Genetic mutations Signup and view all the answers

Study Notes

Aflatoxins

Aflatoxins are polycyclic, unsaturated, and coumarin derivatives from yeast (Aspergillus flavus and A. parasiticus)
Human exposure to aflatoxins occurs through food consumption, particularly through contaminated groundnuts (green) and maize (brown spots)
Aflatoxin B1 is a co-factor in 60% of liver cancer cases in Sudan, leading to Hepatocellular carcinoma (HCC)
MOA: Aflatoxin B1 causes p53 mutations, leading to p53 inactivation, proliferation, loss of growth control, and genetic alterations resulting in HCC
Visible as yellow patches in the liver, causing damage to DNA

Mechanisms of Tox

Genotox

Degradation Methods

Extruder
Ammonia

Snake Venom

Anatomy of Venomous Snakes

Venom glands release venom through pressure on compressor muscle (in the ‘cheek’) and via venom duct into fangs and into tissue
Examples: Rattle snakes, black mamba

Toxins in Snake Venom

Phospholipase A2: local and systemic myotox, pain, damage to lymphatic vessels, oedema, neurotox, nephrotox, and hemolysis
Snake venom metalloproteinases (SVMP): hemorrhage, myonecrosis, extracellular matrix degradation, blistering, pain, oedema, cardiovascular shock, nephrotox, and coagulopathy
Hyaluronidases: ECM degradation
Three finger toxins: cytotox, necrosis, and neurotox
Dendrotox: neurotox
Snake venom serine proteinases (SVSP): coagulopathy, oedema, and hypotension
Vasoactive peptides: hypotension
Disintegrins: inhibition of platelet aggregation
C-type lectin like proteins: inhibition or promotion of platelet aggregation and thrombocytopenia
Cysteine-rich secretory proteins: smooth muscle paralysis
Natriuretic peptides: hypotension
Sarafotoxins: cardiotox

Symptoms of Envenomation

Swelling and blistering
Gangrene
Bleeding gums
Skin necrosis
Paralysis of eye muscles and upper eyelid

Mechanism of Neurotox

Capturing Snake Venom

Snake venom milking
Advantages: qualitative and quantitative information about toxins present, development of antivenom
Capturing toxins: antivenom immobilization, column with venom Ab, toxins bind, rest goes through, elution, and further characterization
Toxins are promising for treatment of cerebro and cardiovascular diseases, arteriosclerosis, blood clotting diseases, wound healing, hypertension, cancer, and viral infections

TGN1412

Medicine supposed for treatment of B-cell lymphatic leukemia and rheumatoid arthritis
MOA: normal trigger of immune response, Ag binds T-cell R, co-stimulatory molecule (CD28) for the activation of immune cells

MOA for Disease

Activation of CD4+ T-cells, no longer tolerance to leukemic B-cells, elimination of leukemic B-cells
Activation of T-reg (also have expression of CD28)
Activation of other lymphocytes T4

MOA of Tox

Cytokine storm: very high number of cytokines (first days after infusion), headache, hypotension, tachycardia, fever, lymphopenia, monocytopenia
Cortico injection (reduction of immune response) = transient improvement
Multi-organ failure, ↑ ALT (liver damage), necrosis of extremities

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Description

This module covers the toxicity of aflatoxins, including their sources, human exposure, and health effects such as hepatocellular carcinoma. Aflatoxins are polycyclic, unsaturated coumarin derivatives from Aspergillus flavus and A. parasiticus.

Module 9: Organ-Specific Toxicity - Aflatoxins

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