Drug Biotechnology Multiple Choice Questions on “Bioactivation and Tissue Toxicity”.
1. Which of the following statement rightly states “bioactivation”?
a) Formation of high reactive metabolites which interact with tissues to precipitate toxic compounds
b) Formation chelating agents
c) Formation of enzymes which can lyse toxic compounds
d) Stimulating the immune systems to initiate the formation of t cells
Answer: a
Clarification: Formation of highly reactive metabolites which can interact with the tissues and precipitate out various toxic compounds such as carcinogens, teratogens, etc. is known as bioactivation or toxicological activation.
2. Which of the following is an example of electrophiles?
a) Thalidomide
b) Aflatoxin
c) Epoxides
d) Benzopyrene
Answer: c
Clarification: Electrophiles are species deficient in electron pair. Important electrophiles are epoxides, hydroxylamines, nitroso, and azoxy derivatives, nitrenium ions, and elemental sulphur.
3. What is the body’s defence against electrophiles?
a) Their inactivation by conjugation with glucagon
b) Their inactivation by conjugation with glutamine
c) Their inactivation by conjugation with glucuronic acid
d) Their inactivation by conjugation with glutathione
Answer: d
Clarification: The body’s defence against electrophile is their inactivation by conjugation with glutathione, the most abundant cellular nucleophile wit –SH group. Example of tissue toxicity due to electrophiles is hepatotoxicity of paracetamol metabolites.
4. Electrophiles are deficient of pair of electrons and free radicals contain an odd number of electrons.
a) True
b) False
Answer: a
Clarification: Electrophiles are the species which are deficient in a pair of electron. These electrophiles in our body are generated through cytochrome P-450. Free radicals are species containing an odd number of electrons. These may be positively charged, negatively charged or neutral. Free radicals are formed via NADPH cytochrome P-450 reductase.
5. Which xenobiotics yield free radicles on metabolic activation?
a) Thalidomide
b) Aflatoxin
c) Quinones
d) Benzopyrene
Answer: c
Clarification: Quinones, arylamines, nitroaryls and carbon tetrachloride are some of the examples of xenobiotics which yields free radicals. Endogenous compounds such as epinephrine, DOPA can generate free radicals.
6. Which of the following will be an example of inorganic free radicle?
a) H2O2 and O2–
b) Aflatoxin
c) Quinones
d) Benzopyrene
Answer: a
Clarification: Most free radicles are organic. Some of the examples of inorganic free radicles are H2O2 and O2 and O2-. These oxidative moieties can cause tremendous tissue damage leading to mutations and cancer. The potential toxicity of free radicals is more than electrophiles.
7. How are electrophiles generated?
a) Through cytochrome P-450 system
b) NADPH cytochrome P-450 reductase
c) Different Flavin containing reductase
d) Through cytochrome P-350 system
Answer: a
Clarification: Electrophiles are species deficient in electron pair. The enzyme system through which they are generated is cytochrome-P450. Carbon, nitrogen, sulphur compounds can be metabolically activated to yield electrophiles.
8. How are free radicals generated in the human body?
a) Through cytochrome P-450 system
b) NADPH cytochrome P-450 reductase
c) NADPH reductase
d) Through cytochrome P-350 system
Answer: b
Clarification: Free radicles are formed via NADPH cytochrome P-450 reductase or other Flavin containing reductases. Quinones, arylamines, nitroaryls and carbon tetrachloride are some of the examples of xenobiotics which yields free radicals. Endogenous compounds such as epinephrine, DOPA can generate free radicals.
9. Free radicals are more dangerous than electrophiles.
a) True
b) False
Answer: a
Clarification: Some of the examples of inorganic free radicles are H2O2 and O2–. These oxidative moieties can cause tremendous tissue damage leading to mutations and cancer. The potential toxicity of free radicals is more than electrophiles.
10. Bioavailability of glutathione in the body doesn’t determine the threshold of a toxic response.
a) True
b) False
Answer: b
Clarification: The generation of reactive metabolites is indicated by modification in enzyme activities, the formation of glutathione conjugates and depletion of tissue levels of glutathione. Thus, the bioavailability of glutathione in the body determines the threshold of a toxic response.