Xenobiotic-induced oxidative stress: cell injury, signaling and gene regulation
19 important questions on Xenobiotic-induced oxidative stress: cell injury, signaling and gene regulation
What is the stepwise reduction of molecular oxygen?
1) molecular oxygen
2) superoxide anion radical
3) hydroxen peroxide
4) hydroxyl radical
5) water
What is redox cycling?
What can be the toxicological consequences of repeated reduction and oxidation of a xenobiotic?
2) a single molecule can generate numerous molecules of superoxide.
3) This process will continue until the supply of reducing equivalents (NADPH) is exhausted or can no longer be regenerated.
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What are features of the quinones?
How works oxidative stress generating by CYPs?
How works superoxide dismutase?
How works the Fenton reaction?
In what way can copper play a role in the toxicology?
What are the 2 reasons that bleomycin only induces lung toxicity?
- The lung has a high pO2 what favors the formation of ROS.
What is the mechanism behind NO toxicity?
- It can react with superoxide anion in ONOO- (peroxynitrite). Which is faster than the reaction with SOD.
Why are erythrocytes very sensitive to oxidative stress?
2) high oxygen concentration
3) xenobiotics are in most cases distributed to the blood in high concentrations.
What are Heinz bodies?
Why is lipid oxidation different?
- The alkoxy radicals that are generated can be in a same way toxic as ROS.
In what way lipid peroxidation can occur?
2) Conjugated diene. (the electron is moving)
3) molecular oxygen is added and the result is a lipid peroxyl radical
Chain reaction can occur because again a hydrogen is abstracted from another lipid which will result in more reactive lipids.
1) Fenton reaction can occur resulting in a hydroxyl then fragmentation will occur.
resulting in aldehyde degradation products.
What are features of glutathione?
2) glutamate and cystein are not normally coupled to each other via the alpha carbon but via the gamma carboxy group. This protects it from protease digestion.
3) GSH reaches high steady state concentrations and these are maintained.
Via which enzyme is glutathione synthesized?
Which three pivotal tasks are at least fulfilled by GSH?
- cosubstrate for enzymatic degradation of H2O2.
- Is involved in the regeneration of oxidized proteins and keeps the cell in a reduced state.
What are the mechanisms of SOD-protection against ethanol induced oxidative stress in the liver?
What are the mechanisms of oxidative stress mediated gene regulation?
- oxidative damage to macromolecules (direct damage)
- There are also redox sensors that can activate transcription factors and kinases.
- This will result in gene (in)activation
- This will result in cell adaptation, cell proliferation or damage.
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