Chapter 7: Cellular and Tissue Targets of Toxicity Flashcards
What is the target molecule concept in toxicology?
The target molecule concept in toxicology refers to the idea that somewhere in the body is a molecule that a toxicant can affect, and the adverse effect only happens if the toxicant is at a sufficient concentration at the target.
What is toxicodynamics in toxicology?
Toxicodynamics in toxicology refers to what happens after the target molecule is altered by a toxicant, which can result in all types of molecular, cellular, and organ damage.
How can exposure to toxicants result in alterations in gene expression?
Exposure to toxicants can result in alterations in gene expression. If a toxicant has high affinity to certain cellular receptors, it may directly alter the expression of certain genes through receptor complexes (ie: bifenthrin). Alternatively, if a toxicant binds to certain types of receptors, it may activate a cell signaling pathway(s) that can lead to altered gene expression.
What are reactive oxygen species (ROS)?
Reactive oxygen species (ROS) are free radicals, which are atoms or molecules that have a single unpaired electron, such as O2˙, HO˙, and H2O2.
How do cells deal with reactive oxygen species (ROS)?
Cells deal with reactive oxygen species (ROS) by removing superoxide radical (O2-) through enzymes such as superoxide dismutase (SOD), glutathione peroxidase (GPX), and catalase (CAT). However, no enzyme eliminates HO* due to its extremely short half-life (10-9 s).
What can some toxicants cause?
Some toxicants can cause destruction of target molecules.
What is an example of a toxicant that can cause destruction of target molecules?
An example of a toxicant that can cause destruction of target molecules is reactive oxygen species (ROS).
What is Step 1 in the process of lipid peroxidation?
Step 1 is when a hydroxyl radical reacts with an unsaturated lipid to form a lipid radical.
What can stop the chain reaction of lipid peroxidation?
Tocopherol (Vitamin E) can stop the chain reaction of lipid peroxidation by donating an electron.
What happens after Tocopherol donates an electron to stop the chain reaction of lipid peroxidation? (Step 3)
After passing on the electron, the peroxyl radical is turned into a lipid peroxide, that forms aldehydes that can bind with biomolecules, trigger apoptosis, etc. This is Step 3.
What is Step 2 in the process of lipid peroxidation?
Step 2 is when the lipid radical combines with O2 to form a peroxyl radical, which can pass on the free electron to another unsaturated lipid. This occurs again and again!
What is the effect of some toxicants on cell function?
Some toxicants cause dysregulation of cell function.
How do toxicants bind and alter the function of a target molecule?
Toxicants bind to and alter the function of a target molecule, but there is a lot of variation in how this can happen.
What are the three critical ways that toxicants can disrupt cell function?
The three critical ways that toxicants can disrupt cell function are ATP depletion, sustained rise in intracellular Ca2+, and overproduction of ROS (and RNS).
How does ATP depletion affect cell function?
Any toxicant that interferes with aerobic metabolism will decrease the overall levels of ATP in the cell. Without enough ATP, cells cannot carry out normal functions, such as active transporters (ion pumps) and maintaining homeostasis.