Lipid oxidation products inflammatory responses

Hepatic reperfusion injury is not a phenomenon connected solely to liver transplantation but also to situations of prolonged hypoperfusion of the host s own liver. Examples of this occurrence are hypovolemic shock and acute cardiovascular injur) (heart attack). As a result of such cessation and then reintroduction of blood flow, the liver is damaged such that centrilobular necrosis occurs and elevated levels of liver enzymes in the serum can be detected. Particularly because of the involvement of other organs, the interpretation of the role of free radicals in ischaemic hepatitis from this clinical data is very difficult. The involvement of free radicals in the overall phenomenon of hypovolemic shock has been discussed recently by Redl et al. (1993). More specifically. Poll (1993) has reported preliminary data on markers of free-radical production during ischaemic hepatitis. These markers mostly concerned indices of lipid peroxidation in the serum and also in the erythrocytes of affected subjects, and a correlation was seen with the extent of liver injury. The mechanisms of free-radical damage in this model will be difficult to determine in the clinical setting, but the similarity to the situation with transplanted liver surest that the above discussion of the role of XO activation, Kupffer cell activation and induction of an acute inflammatory response would be also relevant here. It will be important to establish whether oxidative stress is important in the pathogenesis of ischaemic hepatitis and in the problems of liver transplantation discussed above, since it would surest that antioxidant therapy could be of real benefit. 

The iron or haemoprotein catalysed oxidative reactions may mediate the responses associated with acute and chronic inflammation. In the post-ischaemic, reperfused heart the role of oxidant stress has been linked with increases in leucocyte adhesion and transendothelial cell migration from oxidant production within the microcirculation [115]. This is probably caused by an increased expression in adhesion molecules or the fixation of transiently expressed adhesion molecules by the peroxidation of membrane lipids which reduces membrane fluidity [117,118]. This oxidant stress may also lead to apoptosis induction, DNA damage, inflammatory mediator synthesis and regulate gene expression [119,120,121]. 

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