Lipid oxidation products stress modulation

Abstract Since the discovery of oxidized phospholipids (OxPL) and their implication as modulators of inflammation in cardiovascular disease, roles for these lipid oxidation products have been suggested in many other disease settings. Lipid oxidation products accumulate in inflamed and oxidatively damaged tissue, where they are derived from oxidative modification of lipoproteins, but also from membranes of cells undergoing apoptosis. Thus, increased oxidative stress as well as decreased clearance of apoptotic cells has been implied to contribute to accumulation of OxPL in chronically inflamed tissues. 

DOM treatment also rapidly decreases cellular GSH, which precedes neurotoxicity. This decrease is primarily due to DOM-mediated GSH efflux. DOM also induces an increase in oxidative stress as indicated by increases in ROS and lipid peroxidation products, which follow GSH efflux. Astrocytes from both genotypes are resistant to DOM-mediated neurotoxicity and present a diminished Ca2+ response to DOM-mediated toxicity (Walser et al., 2006). Exposure of neonatal rat microglia to DOM triggers the release of TNF-a and matrix metalloproteinase-9 (MMP-9) (Mayer et al., 2001). These molecules are involved in the modulation of neuroinflammation in brain (Farooqui et al., 2007). Collective evidence suggests that DOM-mediated neurodegeneration involves changes in cellular redox, oxidative stress, and increased expression of cytokines, nitric oxide synthase, NADPH diaphorase, and matrix metalloproteinase-9 (Walser et al., 2006 Chandrasekaran et al., 2004 Ananth et al., 2003a,b Mayer et al., 2001). 

There are four criteria for involvement of free radical processes in toxicity. The first is the detection of the free radical metabolite either with ESR or by its unique reaction product. The second is the in vitro demonstration that free radicals are involved in the biochemical mechanisms of toxicity (i.e., covalent binding, lipid peroxidation, oxidative stress, etc.). In addition, either the third criterion, the common symptom test , i.e., production of similar toxicity by otherwise dissimilar chemicals which produce free radicals with common chemistry or, alternatively, the fourth criterion, the ability to modulate the toxicity through administration of antioxidants or free radical scavengers needs to be met before a toxicity can be considered to be caused by formation of free radicals. In summary three questions must be answered. First, does a... 

Nearly all ischemic events are modulated by temperature, and cerebroprotection from hypothermia is believed to increase resistance against multiple deleterious pathways including oxidative stress and inflammation [205-211]. Generally, most biological processes exhibit a of approximately 2.5, which means that a 1°C reduction in temperature reduces the rate of cellular respiration, oxygen demand, and carbon dioxide production by approximately 10% [212]. Reduced temperature also slows the rate of pathological processes such as lipid peroxidation, as well as the activity of certain cysteine or serine proteases. However, detoxification and repair processes are also slowed, so the net outcome may be complex. Hence, hypothermia appears to be an attractive therapy that targets multiple injury mechanisms. 

It is evident that variations in thyroid hormone levels are among the main physiological modulators of in vivo cellular oxidative stress. The hypermetabolic state in hyperthyroidism is associated with increases in free radical production and lipid peroxidation (LP), and the hypomet-abolic state in hypothyroidism is generally associated with a decrease in free radical production and LP in most tissues (Fernandez et ai, 1985 Venditti et ai, 1997). The development of a hyperthyroid state in vertebrates leads to enhancement of their basal metabolic rate due to an increase in the rate of O2 consumption in most tissues, excluding the spleen, testis and adult brain (Barker and Klitgaard, 1952). Thyroid hormones were shown... 

---