Oxidant induced lipid peroxidation

Oboh, G., Rocha, J. B. T. (2007). Polyphenols in red pepper (C 5>s c m annum weat aviculare Tepiri) and their protective effects on some pro-oxidant induced lipid peroxidation in brain and liver. European Food Research and Techrwlogy, 225, 239-247. 

Prolonged inhalation of dusts by humans (156), rodents (157,158), and other species (159,160) is associated with an increase in the number of type II cells and increased secretion of surfactant. The stimulation of surfactant appears to be directly related to the toxicity of the dust. It may be so florid, as in acute silicosis, that flooding of the alveolar spaces with surfactant lipids and associated proteins may occur, a condition known as alveolar lipoproteinosis (156). In experimental lipoproteinosis in the rat, the major lipid component is disaturated phosphatidylcholine (157), but all lipid fractions are increased. In the sheep model of experimental silicosis, phosphatidylglycerol, phosphatidylethanolamine, and phosphatidylinositol, showed the greatest increases following silica exposure (159). The excess production of surfactant in response to silica dust may be an adaptive response, perhaps to reduce particle cytotoxicity or to compensate for oxidant-induced lipid peroxidation (147,161). 

Copper salts such as CuS04 are potent catalysts of the oxidative modification of LDL in vitro (Esterbauer et al., 1990), although more than 95% of the copper in human serum is bound to caeruloplasmin. Cp is an acute-phase protein and a potent inhibitor of lipid peroxidation, but is susceptible to both proteolytic and oxidative attack with the consequent release of catalytic copper ions capable of inducing lipid peroxidation (Winyard and... 

Treatment with iron chelators and a-tocopherol protect against lipid p>eroxidation and hepatocellular injury in iron-overloaded rats (Sharma etal., 1990). When hepatocytes are isolated from rats, which have been pretreated with a-tocopherol, there is a significant reduction in iron-induced lipid peroxidation and improvement in cell viability in vitro (Poli et al., 1985). Similar effects were seen when hepatocytes were incubated with iron chelators (Bacon and Britton, 1990). Treatment of moderately, but not heavily, iron-loaded rats with desferrioxamine in vivo inhibits the pro-oxidant activity of hepatic ultrafiltrates (Britton et al., 1990b). 

Jewell, S.A., DiMonte, D., Richelmi, P., Bellomo, G. and Orrenius, S. (1986). tert-Butylhydroperoxide-induced toxicity in isolated hepatocytes contribution of thiol oxidation and lipid peroxidation. J. Biochem. Toxicol. 1, 13-22. 

The phenothiazines, chlorpromazine and promethazine, have been described as inhibitors of CCU-induced lipid peroxidation at relatively high concentrations in rat liver microsomes (Slater, 1968). Structural modifications of chlorpromazine were undertaken to try to increase antioxidant activity and maintain molecular lipophilicity. The 2-N-N-dimethyl ethanamine methanesulphonate-substituted phenothiazine (3) was found to be a potent inhibitor of iron-dependent lipid peroxidation. It was also found to block Cu -catalysed oxidation of LDL more effectively than probucol and to protect primary cultures of rat hippocampal neurons against hydrogen peroxide-induced toxicity in vitro (Yu et al., 1992). 

As a rule, oxygen radical overproduction in mitochondria is accompanied by peroxidation of mitochondrial lipids, glutathione depletion, and an increase in other parameters of oxidative stress. Thus, the enhancement of superoxide production in bovine heart submitochondrial particles by antimycin resulted in a decrease in the activity of cytochrome c oxidase through the peroxidation of cardiolipin [45]. Iron overload also induced lipid peroxidation and a decrease in mitochondrial membrane potential in rat liver mitochondria [46]. Sensi et al. [47] demonstrated that zinc influx induced mitochondrial superoxide production in postsynaptic neurons. 

Numerous studies were dedicated to the effects of flavonoids on microsomal and mitochondrial lipid peroxidation. Kaempferol, quercetin, 7,8-dihydroxyflavone and D-catechin inhibited lipid peroxidation of light mitochondrial fraction from the rat liver initiated by the xanthine oxidase system [126]. Catechin, rutin, and naringin inhibited microsomal lipid peroxidation, xanthine oxidase activity, and DNA cleavage [127]. Myricetin inhibited ferric nitrilotriacetate-induced DNA oxidation and lipid peroxidation in primary rat hepatocyte cultures and activated DNA repair process [128]. 

Figure 2. NO inhibits iron-induced lipid peroxidation. The rate of Oj consumption of HL-60 cells (5 X 10 /ml) was detennined using a YSI O2 monitor. Fe (20 pM) was added at the first arrow and subsequently NO (0.45 pM) was added (other arrows). When NO was added, the O2 consumption was inhibited for a period of a few min, then it resumed at near its initial rate until the reintroduction of additional NO. Also shown (lower dashed line) is a control of HL-60 cells subjected to Fe -induced oxidative stress in the absence of NO addition. The background rate of O2 uptake of the HL-60 cell suspension before the addition of Fe was 10 nM/sec. Upon the addition of 20 pM Fe, this rate increased to 220 nM/sec. The addition of NO resulted in a decrease in O2 consumption to <10 nM/sec. (From Kelley, E.E., Wagner, B.A., Buettner, G.R., and Bums, C.P., 1999, Arch. Biochem. Biophys. 370 97-104).

As discussed above, ufa, which are present primarily in cellular membranes, appear to be particularly susceptible to oxidative degradation by ozone. Various studies of membrane lipid peroxidation have implicated this process in damage to organelles, including mitochondria, micro-somes, and lysosomes, as well as to the cell membrane itself. By analogy, it is conceivable that many of the findings in cells and subcellular components described in other sections of this chapter are secondary to ozone-induced lipid peroxidation. However, this remains conjectural. 

The superoxide oxide radical interacts with nitric oxide to produce peroxynitrite at a rate which three times faster than the rate at which superoxide dismutase utilizes superoxide (Beckman, 1994). Peroxynitrite is capable of diffusing to distant places in neural cells where it induces lipid peroxidation and may be involved in synaptosomal and myelin damage (Van der Veen and Roberts, 1999). After protonation and decomposition, peroxynitrite produces more hydroxyl radicals. This mechanism of hydroxyl radical generation is not dependent on redox active metal ions and may be involved in initiating lipid and protein peroxidation in vivo (Warner et al., 2004). 

Radicals such as CCI3, produced during the oxidation of carbon tetrachloride, may induce lipid peroxidation and subsequent destruction of lipid membranes (Figure 8.3). Because of the critical nature of various cellular membranes (nuclear, mitochondrial, lysosomal, etc.), lipid peroxidation can be a pivotal event in cellular necrosis. 

Figure 8.3 Pomegranate juice consumption reduces serum and LDL oxidation in humans and in atherosclerotic E° mice. Mean ( SD) effect of 2 and 9 weeks of PJ supplementation to 13 healthy men and to E° mice (A and B, respectively) on the susceptibility of serum to radical-induced lipid peroxidation and copper ion-induced LDL oxidation (C and D, respectively) is shown. = p < 0.01 (after vs. before PJ consumption in humans, and PJ vs. control in mice).

Fuhrman, B., Oiknine, J., and Aviram, M., Iron induces lipid peroxidation in cultured macrophages, increases their ability to oxidatively modify LDL and affect their secretory properties, Atherosclerosis, 111, 65, 1994. 

A. Casini, E. Ceni, R. Salzano, P. Biondi, M. Parola, A. Galli, M. Foschi, A. Caligi-uri, M. Pinzani, and C. Surrenti, Neutrophil-derived superoxide anion induces lipid peroxidation and stimulates collagen synthesis in human hepatic stellate cells role of nitric oxide, Hepatology 25 361-367 (1997). 

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