Introduction: This MCQ set on “Antioxidants: protective activities and therapeutic uses” is crafted for M.Pharm students studying Advanced Pharmacology-II. It covers fundamental mechanisms of reactive oxygen species (ROS) generation and the cellular antioxidant defense systems, including enzymatic and non-enzymatic antioxidants. Questions examine pharmacological actions, clinical indications, molecular targets such as Nrf2 and selenoproteins, biomarker evaluation, pro-oxidant risks, and therapeutic agents like NAC, vitamin E isoforms, SOD mimetics and metal chelators. Emphasis is placed on translational and therapeutic considerations, drug interactions, dosing, and evidence from clinical studies to prepare students for advanced exams and practical decision-making in oxidative stress–related therapies.
Q1. What is the primary biochemical event that initiates lipid peroxidation in biological membranes?
- Direct enzymatic oxidation by cyclooxygenase
- Hydrogen abstraction from polyunsaturated fatty acids by ROS
- Spontaneous hydrolysis of phospholipids
- Cross-linking of membrane proteins
Correct Answer: Hydrogen abstraction from polyunsaturated fatty acids by ROS
Q2. Which antioxidant enzyme catalyzes the dismutation of superoxide anion into hydrogen peroxide and oxygen?
- Glutathione peroxidase
- Catalase
- Superoxide dismutase
- Thioredoxin reductase
Correct Answer: Superoxide dismutase
Q3. N-acetylcysteine (NAC) primarily exerts its antioxidant effect by which mechanism?
- Direct scavenging of hydroxyl radicals with high affinity
- Serving as a precursor to intracellular glutathione synthesis
- Chelating free iron to prevent Fenton reactions
- Inhibiting NADPH oxidase enzymatic activity
Correct Answer: Serving as a precursor to intracellular glutathione synthesis
Q4. Which biomarker is most specific for oxidative damage to DNA?
- Malondialdehyde (MDA)
- Protein carbonyls
- 8-hydroxy-2′-deoxyguanosine (8-OHdG)
- F2-isoprostanes
Correct Answer: 8-hydroxy-2′-deoxyguanosine (8-OHdG)
Q5. Which vitamin can act as a pro-oxidant under conditions of high free transition metal availability?
- Vitamin K
- Vitamin C (ascorbate)
- Vitamin A (retinol)
- Vitamin B12
Correct Answer: Vitamin C (ascorbate)
Q6. Which class of antioxidants functions primarily by chelating catalytic metal ions to inhibit Fenton chemistry?
- Chain-breaking antioxidants (e.g., vitamin E)
- Metal chelators (e.g., deferoxamine)
- Enzymatic antioxidants (e.g., catalase)
- Peroxynitrite scavengers (e.g., uric acid)
Correct Answer: Metal chelators (e.g., deferoxamine)
Q7. Which selenoprotein is directly involved in reducing hydrogen peroxide and lipid hydroperoxides using glutathione?
- Thioredoxin
- Glutathione peroxidase
- Selenoprotein P
- Peroxiredoxin 6
Correct Answer: Glutathione peroxidase
Q8. Activation of the Nrf2 signaling pathway leads to increased expression of which type of genes?
- Pro-apoptotic caspases
- Phase II detoxification and antioxidant enzymes
- Pro-inflammatory cytokines
- Glycolytic enzymes only
Correct Answer: Phase II detoxification and antioxidant enzymes
Q9. Which of the following therapeutic uses of antioxidants is supported by strong clinical evidence?
- High-dose vitamin E for prevention of all-cause mortality
- N-acetylcysteine in acetaminophen (paracetamol) overdose
- Large-dose beta-carotene supplements for lung cancer prevention in smokers
- Vitamin C megadoses to cure the common cold
Correct Answer: N-acetylcysteine in acetaminophen (paracetamol) overdose
Q10. Which antioxidant is lipid-soluble and protects cell membranes from lipid peroxidation by donating a hydrogen atom to lipid radicals?
- Glutathione
- Ascorbic acid
- Alpha-tocopherol (vitamin E)
- Uric acid
Correct Answer: Alpha-tocopherol (vitamin E)
Q11. SOD mimetics used therapeutically primarily aim to replicate which biochemical activity?
- Reduction of hydrogen peroxide to water
- Dismutation of superoxide radicals to hydrogen peroxide and oxygen
- Direct scavenging of hydroxyl radicals
- Inhibition of nitric oxide synthase
Correct Answer: Dismutation of superoxide radicals to hydrogen peroxide and oxygen
Q12. In cardiovascular disease, which oxidative marker derived from arachidonic acid non-enzymatic peroxidation is considered a reliable in vivo indicator of lipid peroxidation?
- Malondialdehyde (MDA)
- F2-isoprostanes
- 8-OHdG
- Protein nitrotyrosine
Correct Answer: F2-isoprostanes
Q13. Which statement best describes the “redox cycling” property that can make some phenolic antioxidants act as pro-oxidants?
- Phenolics irreversibly bind to lipid radicals preventing regeneration
- Phenolics repeatedly donate and re-receive electrons in the presence of transition metals, generating ROS
- Phenolics are permanently oxidized and excreted without effect
- Phenolics activate catalase, increasing peroxide levels
Correct Answer: Phenolics repeatedly donate and re-receive electrons in the presence of transition metals, generating ROS
Q14. Which therapeutic antioxidant is an approved drug for reducing iron burden and preventing iron-catalyzed oxidative damage in thalassemia?
- Deferasirox
- Vitamin C
- Alpha-lipoic acid
- Glutathione
Correct Answer: Deferasirox
Q15. Which intracellular molecule provides the reducing equivalents for glutathione reductase to regenerate reduced glutathione (GSH) from oxidized glutathione (GSSG)?
- NADH
- NADPH
- FADH2
- ATP
Correct Answer: NADPH
Q16. Which clinical concern is most relevant when prescribing high-dose antioxidant supplements to patients undergoing chemotherapy?
- Antioxidants may enhance chemotherapy-induced oxidative damage
- Antioxidants may reduce efficacy of pro-oxidant chemotherapeutic agents by protecting tumor cells
- Antioxidants always increase chemotherapy toxicity in normal tissues
- Antioxidants cause irreversible DNA crosslinking with alkylating agents
Correct Answer: Antioxidants may reduce efficacy of pro-oxidant chemotherapeutic agents by protecting tumor cells
Q17. Which endogenous molecule is the most abundant intracellular non-enzymatic antioxidant and is critical for phase II conjugation reactions?
- Ascorbate
- Glutathione (GSH)
- Uric acid
- Coenzyme Q10
Correct Answer: Glutathione (GSH)
Q18. Which therapeutic antioxidant has been studied for preventing contrast-induced nephropathy due to its ROS-scavenging and vasodilatory properties?
- N-acetylcysteine (NAC)
- Vitamin B6
- Deferoxamine
- Alpha-tocopherol
Correct Answer: N-acetylcysteine (NAC)
Q19. Which method is most appropriate for quantifying protein oxidative damage in a biological sample?
- Measuring reduced glutathione by HPLC
- Assessing protein carbonyl content
- Assessing serum vitamin C levels
- Measuring activity of cytochrome P450 enzymes
Correct Answer: Assessing protein carbonyl content
Q20. Which pharmacological approach targets mitochondrial oxidative stress specifically to protect tissues from ischemia-reperfusion injury?
- Systemic high-dose vitamin E supplementation
- Mitochondria-targeted antioxidants (e.g., MitoQ)
- Oral iron chelation only
- Topical ascorbate application
Correct Answer: Mitochondria-targeted antioxidants (e.g., MitoQ)
