Molecular mechanisms of inflammation.
Among a vast number of chemical mediators of inflammation such as histamine, 5-hydroxytryptamine, bradykinin, SRS-A the metabolites of arachidonic acid (AA) attracted vivid attention in the last ten years. Aspirin-like drugs are inhibitors of AA cyclo-oxygenation, while anti-inflammatory steroids inhibit the liberation of AA from phospholipids. These biochemical effects of steroidal and non-steroidal anti-inflammatory drugs lead to a suppression of generation of primary prostaglandins (e.g. PGE2) and therefore the curative action of these drugs has been explained in terms of depletion of pro-inflammatory prostaglandins. Recently, Samuelsson et al. described a new class of AA metabolites--leukotriens. Leukotrien C, which derives from 5-hydroperoxyeicosatetranoic acid and cysteine, is supposed to be SRS-A. The discovery of Samuelsson revived a known idea, that any biochemical transformation of AA (including the cyclo-oxygenase pathway) is initiated by its lipoxydation. Thus formed highly active hydroperoxy fatty acids and deriving oxygen-centred free radicals are important not only for a further biochemical transformation of AA, but also because of their biological action per se. In this respect Kuehl et al. proposed the most interesting idea that a true mediator of inflammation is PGG2 owing to the presence of 15-hydroperoxy group in its molecule, and its capability to generate either TXA2 or free hydroxy radical. It may well be that primary prostaglandins play a secondary role in inflammation, whereas unstable metabolites of AA are the real mediators of inflammation, owing to generation of either destructive free radicals or non-prostaglandin pro-inflammatory mediators (e.g. thromboxane A2, leukotrien C, prostacyclin).
D001095:Arachidonic Acids / Q000378:metabolism*; D001711:Biotransformation; D005609:Free Radicals; D006801:Humans; D007249:Inflammation / Q000209:etiology*; D010084:Oxidation-Reduction; D011453:Prostaglandins / Q000378:metabolism*
D001095:Arachidonic Acids; D005609:Free Radicals; D011453:Prostaglandins