Heparin-iron interaction and its possible relevance to antioxidant activity

• Main Author: Mackintosh, Gillian
• Published: University of Aberdeen 1995
• Subjects: 572; Polysaccharides
• Online Access: http://ethos.bl.uk/OrderDetails.do?uin=uk.bl.ethos.323399

Polysaccharides, such as heparin, are known to interact with a wide range of micro-and macro-cations; this is central to their many and varied biological functions. Iron plays a central role <I>in vivo</I>, participating in both essential and damaging reactions. Iron is normally complexed to transport and storage proteins and seldom exists 'free' <I>in vivo</I>; however, in inflamed tissues, iron can be released from these proteins. This 'free' iron may be involved in radical-generating reactions, which are associated with the development of areas of chronic inflammation. In addition, mast cell-derived heparin is released into inflamed areas; however the precise role of this heparin is unclear. This thesis is concerned in particular with the interaction between heparin (and heparinoids) and iron. A range of physico-chemical techniques was used to study the interaction between heparin and Fe²⁺ and Fe³⁺ ions. Heparin is shown not only to interact with both Fe²⁺ and Fe³⁺ species, but also to promote the oxidation, hydrolysis and precipitation of iron. The ability of heparin to interact with the modulate the chemistry of iron was considered in relation to the potential antioxidant activity of heparin. It was confirmed using a variety of techniques that heparin is effective in inhibiting Fe²⁺-induced lipid peroxidation <I>in vitro</I> and that heparin, particularly when complexed to Cu²⁺ ions, may be able to accelerate the dismutation of superoxide radicals. The ability of heparin to protect cells from free radical-induced oxidative stress is discussed, and this protection compared to systems where the toxicity does not result from a free radical intermediate. The <I>in vivo</I> anti-inflammatory and anti-tumour activity of heparin was briefly investigated, and results suggest that heparinoids may be particularly effective in inhibiting tumour growth and accompanying inflammation.