Table 1.

Stimuli that trigger oxidative stress in cells or in the CNS, similar to the SARS-CoV-2 action.

Stimuli	Model/Species	Disease Model	Administration/Protocol	Mechanism of Oxidative Stress	Ref.
N-methyl- 4-phenyl-1,2,3,6-tetrahydropyridine (MPTP)	Male C57BL/6 mice (20–25 g)	PD, neurodegeneration	Intraperitoneal injection of MPTP (20 mg/kg), two times at 4 h intervals daily for 5 days, followed by oral administration of Sophora tomentosa (25 mg/kg, 50 mg/kg, and 100 mg/kg) for 15 consecutive days until behavioral tests	MPTP is taken up by astrocytes or serotonergic neurons, where it is metabolized into 1-methyl-4-pyridinium (MPP+) by monoamine oxidase B. Subsequent uptake of MPP+ via dopamine, serotonin, and norepinephrine transporters induces oxidative stress by inhibiting complex I of the respiratory chain. Selectively destroys the nigrostriatal dopaminergic pathway and thus is widely used as a PD model. Upregulates levels of MDA, α-synuclein overexpression, and GSK-3β phosphorylation in the mouse striatum.	[88]
Rotenone	Rotenone-induced Sprague–Dawley and Lewis rats	PD	Infusion of a 2–3 mg/kg dose of rotenone per day via a jugular vein cannula attached to a subcutaneous osmotic minipump	Inhibits of complex I and degenerates the nigrostriatal dopaminergic pathway associated with hypokinesia and rigidity.	[89]
Paraquat (N, N′-dimethyl-4-4′-bipiridinium)	Human neuroblastoma SH-SY5Y cells	PD	Treated with paraquat (0.5 mM PQ) for 48 h	Increases superoxide levels and neuronal cell death. Decreases dopamine levels in the substantia nigra and increases α-synuclein expression. Decreases protein levels of Nrf2, γGCS levels, and intracellular GSH levels.	[90]
Hydrogen peroxide (H2O2)	SH-SY5Y cells	PD, AD, Huntington’s disease	Incubation with varying concentrations of H2O2 (0 to 250 µM) for 30 min, followed by evaluation of cell viability	Loss of viability <5% at concentrations up to 250 µM H2O2. Cell membrane and DNA damage accompanied by decreased SOD activity but increased GPX activity in cells treated with >50 µM concentration of H2O2.	[91,92]
6-hydroxydopamine (6-OHDA)	SH-SY5Y cells	PD, AD, and dementia	Cells incubated with 200 µM of 6-OHDA for 24 h with or without hyperoxide or NAC pretreatment	Inhibits both complexes I and IV of the respiratory chain and leads to the generation of superoxide, hydrogen peroxide, and hydroxyl radicals.	[93]
Glutamate analog; homocysteate quisqualate ibotenate	Neuronal hybridoma cell line, N18-RE-105 mouse neuroblastoma cells	ALS, AD, dementia, PD, multiple sclerosis (MS)	Continuous exposure of cells to ʟ-glutamate (1–10 mM) or quisqualate (0.1–1.0 mM) for 5 min	Induces cytotoxicity by inhibiting cystine uptake and resulting in lowered glutathione levels, leading to oxidative stress and cell death.	[94,95]
Mycotoxin 3-nitropropionic acid (3-NP)	Male Wistar rats (300–350 g)	Huntington disease	Intraperitoneal administration of 3-NP (10 mg/kg)	Irreversibly inhibits the Krebs cycle and complex II of the respiratory chain. Promotes the generation of hydroxyl radicals, leading to neuronal death. Induces motor dysfunction.	[96]
Buthionine sulfoximine (BSO)	Hippocampus-derived immortalized cell line (HT22)	Chronic psychological stress	Treatment with 1 mM BSO for 14 h	Binds to glutathione synthetase to inhibit glutathione production.	[97]
Tunicamycin	SH-SY5Y cells	Endoplasmic reticulum stress	Incubation with 1 μM tunicamycin	Intracellular accumulation of aggregates of misfolded protein.	[98]
RNAi	Drosophila	Oxidative damage	Knockdown of SOD2 using the Gal4/UAS system to express SOD2 inverted repeat (Sod2-IR) transgenes	Degrades mRNA related to the expression of a specific antioxidant. Increases caspase activity, decreases mitochondrial content, and reduces ATP levels.	[99]