Reaction of low-molecular-mass organoselenium compounds (and their sulphur analogues) with inflammation-associated oxidants

Abstract

Selenium is an essential trace element in mammals, with the majority specifically encoded as seleno-L-cysteine into a range of selenoproteins. Many of these proteins play a key role in modulating oxidative stress, via either direct detoxification of biological oxidants, or repair of oxidised residues. Both selenium- and sulphur-containing residues react readily with the wide range of oxidants (including hydrogen peroxide, radicals, singlet oxygen and hypochlorous, hypobromous, hypothiocyanous and peroxynitrous acids) that are produced during inflammation and have been implicated in the development of a range of inflammatory diseases. Whilst selenium has similar properties to sulphur, it typically exhibits greater reactivity with most oxidants, and there are considerable differences in the subsequent reactivity and ease of repair of the oxidised species that are formed. This review discusses the chemistry of low-molecular-mass organoselenium compounds (e.g. selenoethers, diselenides and selenols) with inflammatory oxidants, with a particular focus on the reaction kinetics and product studies, with the differences in reactivity between selenium and sulphur analogues described in the selected examples. These data provide insight into the therapeutic potential of low-molecular-mass selenium-containing compounds to modulate the activity of both radical and molecular oxidants and provide protection against inflammation-induced damage. Progress in their therapeutic development (including modulation of potential selenium toxicity by strategic design) is demonstrated by a brief summary of some recent studies where novel organoselenium compounds have been used as wound healing or radioprotection agents and in the prevention of cardiovascular disease.

Keywords::

• selenium
• selenoethers
• selenols
• diselenides
• selenocysteine
• selenomethionine
• sulphur
• thiols
• thioethers
• peroxidase
• oxidant
• hypochlorous acid
• peroxynitrous acid
• radical
• hydrogen peroxide
• hypothiocyanous acid

Acknowledgements

Work in the authors laboratories is supported by grants from the Australian Research Council under the ARC Centres of Excellence (CE0561607) and Discovery (DP0988311) Programs, the Novo Nordisk Foundation, and the National Heart Foundation of Australia (Grants in Aid: G09S4313 and G08S3769).

Declaration of interest

The authors report no declarations of interest. The authors alone are responsible for the content and writing of the paper.