Molecular Mechanisms behind Free Radical Scavengers Function against Oxidative Stress

Abstract

Accumulating evidence shows that oxidative stress is involved in a wide variety of human diseases: rheumatoid arthritis, Alzheimer’s disease, Parkinson’s disease, cancers, etc. Here, we discuss the significance of oxidative conditions in different disease, with the focus on neurodegenerative disease including Parkinson’s disease, which is mainly caused by oxidative stress. Reactive oxygen and nitrogen species (ROS and RNS, respectively), collectively known as RONS, are produced by cellular enzymes such as myeloperoxidase, NADPH-oxidase (nicotinamide adenine dinucleotide phosphate-oxidase) and nitric oxide synthase (NOS). Natural antioxidant systems are categorized into enzymatic and non-enzymatic antioxidant groups. The former includes a number of enzymes such as catalase and glutathione peroxidase, while the latter contains a number of antioxidants acquired from dietary sources including vitamin C, carotenoids, flavonoids and polyphenols. There are also scavengers used for therapeutic purposes, such as 3,4-dihydroxyphenylalanine (L-DOPA) used routinely in the treatment of Parkinson’s disease (not as a free radical scavenger), and 3-methyl-1-phenyl-2-pyrazolin-5-one (Edaravone) that acts as a free radical detoxifier frequently used in acute ischemic stroke. The cell surviving properties of L-DOPA and Edaravone against oxidative stress conditions rely on the alteration of a number of stress proteins such as Annexin A1, Peroxiredoxin-6 and PARK7/DJ-1 (Parkinson disease protein 7, also known as Protein deglycase DJ-1). Although they share the targets in reversing the cytotoxic effects of H2O2, they seem to have distinct mechanism of function. Exposure to L-DOPA may result in hypoxia condition and further induction of ORP150 (150-kDa oxygen-regulated protein) with its concomitant cytoprotective effects but Edaravone seems to protect cells via direct induction of Peroxiredoxin-2 and inhibition of apoptosis.

Xanthine oxidase inhibitor ameliorates postischemic renal injury in mice by promoting resynthesis of adenine nucleotides

“…That is, increases in NADH and hypoxanthine during ischemia account for the principal mechanism of ROS production after ischemia/reperfusion by XOD in the kidney (36). GSH is an antioxidant whose level increases by oxidative stimuli, and it detoxifies ROS with the sulfhydryl group (37). Ischemia/reperfusion-induced H 2 O 2 is detoxified by GSH, preventing it from causing oxidative injury.…”

Bacteria in the ageing gut: did the taming of fire promote a long human lifespan?

“…Enzymes that inactivate toxic protein modifications by acting as deglycating enzymes are obvious second line defence systems. For a long time they were elusive, until recent work demonstrated that proteins of the Hsp31 family, generally viewed as molecular chaperones (Natkanska et al ., ), and members of the DJ‐1 family, were in fact deglycases (Ahmadinejad et al ., ). Furthermore, they were involved in genetic diseases.…”

A New Perspective on Appetite Control: Protein Tyrosine Phosphatase 1b (Ptp1b) Inactivation by Oxidative Phytochemicals

“…One interesting but still poorly understood pathway is the activation of NADPH oxidase (NOX) which results in an increase in oxygen superoxide. 5,6 Oxygen superoxide is then converted to hydrogen peroxide (H 2 O 2 ) by superoxide dismutase (SOD). It has been shown that endogenous H 2 O 2 , arisen from insulin stimulation, can inactivate PTP1B, which in turns potentiates insulin signal transiently, 7,8 as illustrated in Figure 2.…”