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Abstract

Nitrones have the general chemical formula X-CH=NO-Y. They were first used to trap free radicals
in chemical systems and then subsequently in biochemical systems. More recently several Nitrones
including PBN (α-phenyl-tert-butylnitrone) have been shown to have potent biological activity in many
experimental animal models. Many diseases of aging including stroke, cancer development, Parkinson’s
disease and Alzheimer’s disease are known to have enhanced levels of free radicals and oxidative stress.
Some derivatives of PBN are significantly more potent than PBN and have undergone extensive commercial
development in stroke. Recent research has shown that PBN-related nitrones also have anti-cancer activity
in several experimental cancer models and have potential as therapeutics in some cancers. Also in recent
observations nitrones have been shown to act synergistically in combination with other antioxidants in the
prevention of acute acoustic noise induced hearing loss. The mechanistic basis of the potent biological
activity of PBN-related nitrones is not known. Even though PBN-related Nitrones do decrease oxidative
stress and oxidative damage, their potent biological anti-inflammatory activity and their ability to alter cellular
signaling processes can not readily be explained by conventional notions of free radical trapping
biochemistry. This review is focused on our observations and others where the use of selected nitrones as
novel therapeutics have been evaluated in experimental models in the context of free radical biochemical
and cellular processes considered important in pathologic conditions and age-related diseases.

Posted with permission by Elsevier: Nitrones as Therapeutics

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