Inflammatory response oxidative damage

The mechanism of action of sulfur mustard is multifaceted and complex, and has been reviewed in some detail by Papirmeister et al. (1991), Hurst and Smith (2008), and Smith et al. (2008). Efforts to understand the mechanisms of sulfur mustard toxicity are ongoing. Basically, sulfur mustard disrupts the interface of the epidermis and basement membrane causing blistering between the epidermis and dermis. Both immediate (immediate cell membrane damage) and delayed phases (secondary effects resulting from inflammatory responses, DNA damage, vascular leakage) have been described for sulfur mustard-induced dermal effects (Somani and Babu, 1989). Many of the toxic effects of sulfur mustard can be attributed to oxidative stress. 

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 inflammatory response changes with time and can be divided into phases. The rapid phase occurs within seconds to minutes and consists of vasodilation, increased blood flow, edema, and pain. The acute phase is characterized by induction of inflammatory genes by NF-kB and other transcription factors. During this phase, moderate amounts of inflammatory mediators are produced. The chronic phase occurs over months to years and is marked by dramatically increased production of inflammatory mediators. The secondary chronic phase of inflammation occurs after years of oxidative damage has degraded blood vessels and tissues. Such chronic inflammation appears to play a role in many disease states, such as arteriosclerosis and cancer. 

Infection Infection is the most common precipitating factor of hemolysis in G6PD deficiency. The inflammatory response to infection results in the generation of free radicals in macrophages, which can diffuse into the red blood cells and cause oxidative damage. 

---