Infection, oxidative stress vitamin

Cystic fibrosis is the most common lethal autosomal-recessive disease, in which oxidative stress takes place at the airway surface [274]. This disease is characterized by chronic infection and inflammation. Enhanced free radical formation in cystic fibrosis has been shown as early as 1989 [275] and was confirmed in many following studies (see references in Ref. [274]). Contemporary studies also confirm the importance of oxidative stress in the development of cystic fibrosis. Ciabattoni et al. [276] demonstrated the enhanced in vivo lipid peroxidation and platelet activation in this disease. These authors found that urinary excretion of the products of nonenzymatic lipid peroxidation PGF2 and TXB2 was significantly higher in cystic fibrotic patients than in control subjects. It is of importance that vitamin E supplementation resulted in the reduction of the levels of these products of peroxidation. Exhaled ethane, a noninvasive marker of oxidative stress, has also been shown to increase in cystic fibrosis patients [277]. 

Numerous reports of elevated concentrations of lipid [57,58], protein [57,58] and DNA [54] oxidation products in CF patients have now been published. Importantly, oxidative stress is not present in all CF patients at all times. Oxidative stress, like the recurring infections, is probably cyclic. Importantly, antioxidant status tends to decrease with age in CF [58], hence older CF patients are particularly susceptible to renewed cycles of pulmonary inflammation. It is tempting to speculate that it is this oxidant/antioxidant imbalance that is responsible, in part, for their decline in lung function with advancing age. The reason for the fall in antioxidant status in CF is not clear, however decreased compliance in taking vitamin supplements may play a role. Alternatively, it is conceivable those repeated cycles of pulmonary inflammation, and associated oxidative stress, also contributes to the decline in antioxidant status. Whatever the exact cause, it is probable that the worsening antioxidant status of the CF adolescent contributes to their deteriorating clinical circumstances. 

Vitamin C is a powerful antioxidant, effective in aqueous solutions, that scavenges free radicals and prevents the breakdown of protein chains. It protects other antioxidants, which is an advantage in situations involving oxidative stress, such as infected or uninfected wounds and in the post-peel healing period. 

An increase of vitamin C and E concentrations in P. vinckei-infected red cells led to the hypothesis that the parasites were able to synthesize these vitamins (quoted in Muller and Kappes, 2007), however, this is not supported by examination of the P. falciparum genome since genes for the synthesis of ascorbate or tocopherol were not found. A deficiency of vitamin C or E has a protective effect in malaria patients possibly because a lack of this anti-oxidant renders the parasites more vulnerable to oxidant stress. 

Before drawing this chapter to a close with some parallels in other age-related diseases, what have we learnt from Alzheimer s disease First, the known genetic mutations affect a small fraction of people with Alzheimer s disease and their effects are delayed until middle age. This delay implies that, as in mice and monkeys, oxidative stress must cross a threshold before neurons die en masse and dementia can be diagnosed clinically. Second, all other known risk factors for Alzheimer s disease, including Down syndrome, ApoE4 and herpes simplex infection, are associated with a rise in oxidative stress. Third, oxidative stress alone is sufficient to cause dementia in old age in people with no known risk factors (about half the people who succumb to dementia in old age). Fourth, factors that lower oxidative stress, such as aspirin and vitamin E, can postpone the onset of dementia by a few years, if not indefinitely. 

The most likely precipitating factor is that, superimposed on general food deficiency, there is a deficiency of the antioxidant nutrients such as zinc, copper, carotene and vitamins C and E (section 7.4.3). As discussed in section 7.4.2.2, the respiratory burst in response to infection leads to the production of oxygen and halogen radicals as part of the cytotoxic action of stimulated macrophages. The added oxidant stress of an infection may well trigger the sequence of events that leads to the development of kwashiorkor. 

---