In Vitro Screening for Antioxidant Activity

The protective “tone” of a tissue against oxidative stress depends on a balance between endogenous antioxidants (enzymatic and non-enzymatic) and the amount of pro-oxidant reactive oxygen lipid peroxides (
1
–
3
). Lipid and cholesterol peroxides are transported in lipoproteins (primarily low-density lipoproteins [LDL]) and these pre-existing peroxides make LDL highly susceptible for propagation reactions (
4
,
5
). Lipid peroxidation is thought to be an important signalling event in triggering pathophysiological change (
6
). Increased levels of these compounds may respond to α-tocopherol, glutathione (GSH), phytonutrients like carotenoids and flavonoids, ascorbate, coenzyme Q10 (ubiquinone), N-acetylcysteine, transresveratol in red wine, and lipoic acid, which have been studied extensively as dietary supplements to improve antioxidant reserve and thereby help regulate oxidative stress (
7
–
17
). Interest in synthetic compounds with radical scavenging activity and those obtained from plant/herbal sources is growing rapidly. Some examples are the nonhormonal, nonglucocorticoid 21-aminosteroids (
18
), sulfonylurea (
19
), enzyme replacement with high molecular weight (MW) polyethylene-superoxide dismutase (SOD) conjugates (
20
), enzyme mimics such as Ebselen that have glutathione peroxidase (GSHPx) and scavenging activity (
2
,
21
), as well as Manganese-based porphyrin and cyclopentane SOD mimetics (
22
,
23
) and GSH mimics (
24
,
25
). Another novel approach is to induce gene expression of antioxidant enzymes by cytokine activation of nuclear factors (
26
).