Toxins, poisoning and overdose (L24)

Question 1

what is toxicology?

Answer 1

the study of the noxious effects of chemicals on living systems

combines:
• pathology 
• pharmacology 
• biochemistry 
• physiology 
• chemistry

Question 2

what is biochemical toxicology

Answer 2

the interaction of xenobiotics with living organisms

Question 3

what are xenobiotics?

Answer 3

foreign compounds 
• therapeutic drugs 
• recreational drugs 
• environmental agents 
• occupational chemicals 
• natural toxins 
• engineered materials

Question 4

what is LD50?

Answer 4

lethal dose

dose causing death in 50% of exposed animals

simplest measurement of toxicology

Question 5

acute toxicity

Answer 5

rapid development whilst chemical or metabolite are still in body

• short lived but may be lethal
• result from single or short term exposure
• easily identified
• may be antidote

Question 6

chronic toxicity

Answer 6

delayed symptoms - develop after chemical excreted

retrospective detection

may be cumulative effect from long term low exposure

Question 7

from exposure to toxicity

Answer 7

exposure site to site of action

reaction of toxicant with target

cellular effect

repair or disrepair

Question 8

mechanisms of toxicity

Answer 8

oxidative stress
• cytotoxicity
• genotoxicity

DNA or protein binding

interaction with specific targets 
• enzymes 
• receptors 
• ion channels 
• membranes

Question 9

reactive oxygen species (ROS)

Answer 9

molecular oxygen can accept electrons to give ROS

O2-• - superoxide anion
O• - oxygen free radical
OH• - hydroxyl radical

Question 10

oxidative stress

Answer 10

imbalance between cellular production of ROS and the ability to detox them / ability to repair damage

Question 11

generation of ROS

Answer 11

oxidative damage to DNA

oxidative damage to proteins

oxidative damage to lipids

depletion of reduced gluthanione (GSH)

loss of cellular homeostasis

Question 12

oxidative damage to DNA

Answer 12

DNA bases become oxidised leading to misincorporations - mutations

Question 13

oxidative damage to proteins

Answer 13

SH groups oxidised leading to aberrant folding

stress proteins
cytokines
antioxidant enzymes
transcription molecules

Question 14

oxidative damage to lipids

Answer 14

membrane damage

lipid per oxidation leads to formation of malondialdehyde

Question 15

depletion of reduced gluthanione (GSH)

Answer 15

GSH plays a key role in removing ROS from the cell

Question 16

loss of cellular homeostasis

Answer 16

increase in [Ca++] inside cell due to damage of Ca++/ATPase pump

leads to pre-programmed cell death

Question 17

DNA adduct

Answer 17

segment of DNA bound to a cancer-causing chemical

Question 18

how does DNA binding cause adduct formation?

Answer 18

direct acting genotoxins
• epoxides, lactones, platinum, amines

pro-carcinogens
• require prior activation by metabolic enzymes to the ultimate carcinogen
• polyaromatic hydrocarbons, aromatic amines

Question 19

protein adduct formation

Answer 19

chemicals or their metabolites react with amino acid residues on proteins
• SH containing, lysine, arginine

can lead to aberrant protein folding
• alters function
• adduct becomes recognised as foreign by immune sensing cells

Question 20

organophosphorus insecticides (OPs)

Answer 20

target acetyl cholinesterase’s, enzyme needed for neurotransmitter regeneration at NMJ and synapses

bind to serine in the active site of acetyl cholinesterase enzyme