4-Hydroxynonenal in the Physiology and Pathology of Malaria

Oxidative stress is the consequence of imbalance between prooxidative reactions and antioxidative responses in the cell. In the pathophysiology of malaria, oxidative stress represents an important aspect of the host–parasite relationship which plays a key role in many fatal end points of the disease. Alteration in redox metabolism may be important in two ways: Prooxidative reactions are central in the host response to successfully combat malaria infection. In malaria patients, plasma lipid peroxides are increased (Das et al. 1990) and red blood cells (RBCs) show increased lipid peroxidation and decreased antioxidative defense parameters. On the other hand, overwhelming oxidative stress seems to be dangerous for the infected host cell and contribute to severe malaria forms with potentially fatal outcome. Oxidative stress interferes with many cellular functions, such as cell proliferation, inflammatory responses, cell adhesion, and chemotaxis – as regulatory or as toxicity element when in excess. Experimental evidence suggests that cellular dysfunctions under oxidative stress are frequently mediated by products of nonenzymatic degradation of polyunsaturated fatty acids (PUFAs). Lipid peroxidation proceeds by free radical chain reactions with lipid hydroperoxides as immediate products. Hydroperoxides are unstable and decompose to a series of aldehydic products able to exert structural and functional damages to cell constituents. Among these products, hydroxyaldehydes, like 4-hydroxynonenal (4-HNE), are of particular interest because they reach relative high concentrations and are more stable as radicals and able to diffuse inside or even outside the cell to reach distant target molecules that they attack to form covalent conjugates. Target molecules are proteins, DNA, and phospholipids. 4-HNE was described for the first time in 1964 and was correctly characterized in 1980 by Esterbauer and colleagues. In 1990 Esterbauer published his first comprehensive review that included chemical and biochemical results as well as cell biology data. It became evident that 4-HNE can be considered as the final mediator and marker of oxidative stress in cells and living organisms. Its binding behavior to exposed sites in macromolecules in and outside the cell can affect and modulate cell functions at very low concentrations without being toxic to cells. Both facts have opened the door for studying the role of the molecule in diseases accompanied by oxidative stress. The entry will comprehensively summarize the evidence-based knowledge on the role of 4-HNE in malaria physiology and pathophysiology.