Free radicals in disease: diabetes, neurodegeneration, cancer MCQs With Answer

Introduction: This quiz set focuses on free radicals and their roles in diabetes, neurodegeneration, and cancer — topics critical for M.Pharm students studying Advanced Pharmacology-II. The questions emphasize mechanistic pathways of reactive oxygen and nitrogen species (ROS/RNS), key enzymatic defenses, biomarkers, and pharmacological strategies to modulate oxidative stress. Topics include mitochondrial ROS, NADPH oxidases, AGE–RAGE signaling, Nrf2-mediated responses, ferroptosis, and clinically relevant antioxidants and inhibitors. These MCQs are designed to deepen understanding of pathophysiology and therapeutic targets, sharpen reasoning for exams, and support evidence-based drug development perspectives in oxidative-stress–related diseases.

Q1. What is the principal intracellular source of excessive reactive oxygen species (ROS) in hyperglycemia associated with diabetes?

• Mitochondrial electron transport chain (complex I/III)
• NADPH oxidase (NOX) activation
• Xanthine oxidase induction
• Uncoupled endothelial nitric oxide synthase (eNOS)

Correct Answer: Mitochondrial electron transport chain (complex I/III)

Q2. Which hyperglycemia-driven pathways collectively contribute to elevated ROS generation in diabetic complications?

• Polyol pathway flux, protein kinase C activation, and formation of advanced glycation end products (AGEs)
• Hexosamine pathway activation only
• Mitochondrial biogenesis increase exclusively
• Decreased fatty acid oxidation alone

Correct Answer: Polyol pathway flux, protein kinase C activation, and formation of advanced glycation end products (AGEs)

Q3. Which biomarker is most commonly used to quantify oxidative DNA damage in clinical and experimental studies?

• Malondialdehyde (MDA)
• 8-hydroxy-2′-deoxyguanosine (8-OHdG)
• Protein carbonyl content
• Total antioxidant capacity (TAC)

Correct Answer: 8-hydroxy-2′-deoxyguanosine (8-OHdG)

Q4. Which enzyme catalyzes the dismutation of superoxide anion (O2•−) to hydrogen peroxide (H2O2) in cells?

• Glutathione peroxidase (GPx)
• Superoxide dismutase (SOD)
• Catalase
• Peroxiredoxin

Correct Answer: Superoxide dismutase (SOD)

Q5. Which transcription factor is the master regulator of inducible antioxidant and phase II detoxifying enzyme expression?

• NF-κB (nuclear factor kappa B)
• HIF-1α (hypoxia-inducible factor 1-alpha)
• Nrf2 (nuclear factor erythroid 2–related factor 2)
• AP-1 (activator protein 1)

Correct Answer: Nrf2 (nuclear factor erythroid 2–related factor 2)

Q6. Which pharmacological agent is used to supply cysteine for glutathione synthesis and is a clinically used antioxidant?

• Ascorbic acid (vitamin C)
• Alpha-tocopherol (vitamin E)
• N-acetylcysteine (NAC)
• Edaravone

Correct Answer: N-acetylcysteine (NAC)

Q7. Peroxynitrite (ONOO−), a potent reactive nitrogen species implicated in neurodegeneration, is formed by reaction between which two radicals?

• Hydroxyl radical (•OH) and nitrogen dioxide (•NO2)
• Hydrogen peroxide (H2O2) and nitrite (NO2−)
• Superoxide (O2•−) and nitric oxide (NO•)
• Lipid peroxyl radical (LOO•) and nitroxyl (HNO)

Correct Answer: Superoxide (O2•−) and nitric oxide (NO•)

Q8. Which of the following is a widely used lipid peroxidation marker measured in plasma and tissues?

• 8-OHdG
• Malondialdehyde (MDA)
• C-reactive protein (CRP)
• Glutathione-S-transferase (GST) activity

Correct Answer: Malondialdehyde (MDA)

Q9. How does oxidative stress primarily impair pancreatic beta-cell function in diabetes?

• By direct inhibition of insulin receptor signaling in peripheral tissues
• By oxidative damage to mitochondrial DNA and ATP production impairing insulin secretion
• By inducing excessive insulin gene transcription leading to ER stress
• By increasing beta-cell proliferation and dedifferentiation

Correct Answer: By oxidative damage to mitochondrial DNA and ATP production impairing insulin secretion

Q10. In Parkinson’s disease pathogenesis, what role does dopamine autoxidation play in oxidative injury?

• Dopamine autoxidation consumes iron and reduces oxidative burden
• Dopamine autoxidation generates hydrogen peroxide and toxic quinones that damage neurons
• Dopamine autoxidation increases glutathione synthesis and neuroprotection
• Dopamine autoxidation exclusively activates synaptic vesicle recycling

Correct Answer: Dopamine autoxidation generates hydrogen peroxide and toxic quinones that damage neurons

Q11. Advanced glycation end products (AGEs) enhance oxidative stress in diabetic vascular disease mainly by which mechanism?

• Directly scavenging superoxide and reducing ROS
• Binding to RAGE and activating NADPH oxidase signaling
• Inhibiting mitochondrial respiration to lower ROS production
• Stimulating insulin secretion to decrease glucose toxicity

Correct Answer: Binding to RAGE and activating NADPH oxidase signaling

Q12. Which molecular intervention is most likely to induce ferroptosis in cancer cells as a therapeutic strategy?

• Activation of catalase
• Inhibition of glutathione peroxidase 4 (GPX4)
• Overexpression of superoxide dismutase (SOD)
• Enhancement of mitochondrial complex I activity

Correct Answer: Inhibition of glutathione peroxidase 4 (GPX4)

Q13. Which key antioxidant enzyme is a selenium-containing selenoprotein essential for detoxifying hydrogen peroxide and lipid hydroperoxides?

• Glutathione peroxidase (GPx)
• Catalase
• Peroxiredoxin 6 (PRDX6)
• Thioredoxin reductase (TrxR)

Correct Answer: Glutathione peroxidase (GPx)

Q14. How do ROS contribute to both initiation and progression of cancer?

• By solely promoting apoptosis and tumor regression
• By inducing DNA damage and mutations while activating redox-sensitive proliferative signaling
• By preventing angiogenesis and inhibiting metastasis
• By exclusively blocking cell cycle progression at G0/G1

Correct Answer: By inducing DNA damage and mutations while activating redox-sensitive proliferative signaling

Q15. Which NADPH oxidase isoform is most consistently implicated in diabetic vascular oxidative stress and endothelial dysfunction?

• NOX2 only
• NOX1 only
• NOX4 (NADPH oxidase 4)
• NOX5 exclusively

Correct Answer: NOX4 (NADPH oxidase 4)

Q16. Excessive activation of poly(ADP-ribose) polymerase (PARP) during oxidative DNA damage leads to cell death primarily through which mechanism?

• Enhanced DNA repair capacity and cell survival
• Depletion of NAD+ and ATP causing energetic collapse and necrotic cell death
• Immediate activation of caspase-dependent apoptosis only
• Direct inhibition of mitochondrial respiration complexes increasing ATP production

Correct Answer: Depletion of NAD+ and ATP causing energetic collapse and necrotic cell death

Q17. Which assay is commonly used to detect intracellular ROS generation by fluorescent measurement in cell-based studies?

• Dichlorofluorescin diacetate (DCFDA) fluorescence assay
• ELISA for tumor necrosis factor-alpha (TNF-α)
• Western blot for catalase expression
• qPCR of antioxidant genes only

Correct Answer: Dichlorofluorescin diacetate (DCFDA) fluorescence assay

Q18. What is the consequence of mitochondrial permeability transition pore (mPTP) opening in response to oxidative stress?

• Enhanced ATP synthesis and improved cell survival
• Release of cytochrome c, loss of membrane potential, increased ROS and initiation of apoptosis/necrosis
• Immediate stabilization of mitochondrial DNA and reduced ROS
• Exclusive activation of autophagy without cell death

Correct Answer: Release of cytochrome c, loss of membrane potential, increased ROS and initiation of apoptosis/necrosis

Q19. Which free radical scavenger has demonstrated clinical benefit and is used acutely in ischemic stroke as a neuroprotective agent?

• Vitamin C (oral high dose)
• Edaravone (radical scavenger)
• Glutathione infusion
• Buthionine sulfoximine (BSO)

Correct Answer: Edaravone (radical scavenger)

Q20. Constitutive activation of Nrf2 in certain tumors contributes to chemoresistance primarily by which mechanism?

• Downregulation of glutathione and phase II enzymes
• Upregulation of antioxidant defenses and drug-detoxifying enzymes, lowering intracellular ROS and drug efficacy
• Increase in pro-oxidant enzyme expression only
• Induction of permanent cell cycle arrest that sensitizes cells to chemotherapy

Correct Answer: Upregulation of antioxidant defenses and drug-detoxifying enzymes, lowering intracellular ROS and drug efficacy

Download