Lipid peroxidation and oxidative stress

Therefore, the metabolite interferes with mitochondrial function and decreases the production of ATP and other important cofactors such as NADH and FADH. Therefore, after repeated use of the drug, mitochondrial integrity is reduced and cellular and overall liver fat oxidation is inhibited. Consequently, fat accumulates, seen as microvesicular steatosis. Electron microscopy shows swollen mitochondria and damaged mitochondrial structures. The accumulated lipid may encourage lipid peroxidation and oxidative stress to occur, causing further damage. 

Fig. 7.3 Reactions showing the generation of ROS during lipid peroxidation and oxidative stress. Hydroxyl radical ( OH) lipid radical ( lipid), peroxyl radical (lipid-OO ) lipid peroxide (lipid-OOH) nitric oxide ( NO) nitrogen dioxide (N02) peroxynitrite anion (ONOO-) hypochlorous acid (HOC1), and hydrogen peroxide (H202)...

It is well known that lipid peroxidation, DNA singlestrand breaks, and other forms of DNA damage occur in response to oxidative stress (Ames et al, 1982). Depletion of reduced glutathione also commonly precedes or accompanies lipid peroxidation and oxidative stress (Muldoon and Stohs, 1991 Omar et al, 1990). In an in vivo study, the effects of ricin administered orally on hepatic lipid peroxidation, nonprotein sulfhydryl content, and DNA singlestrand breaks were assessed in mice (Muldoon et al, 1992). The incidence of hepatic DNA damage increased 2.9-, 2.8-, and 2.4-fold relative to control values at 24, 36, and 48 h post-treatment with ricin, respectively. Hepatic nonprotein sulfhydryl concentration decreased significantly from 51 to 65% to control values at 24, 36, and 48 h post-treatment (Figures 25.2 and 25.3). 

There is also intriguing evidence that (co-3) fatty acids induce apo B degradation via mechanisms that do not involve the conventional proteasomal or lysosomal degradation pathways. In the presence of (cu-3) fatty acids, apo B degradation was shown to occur in a post-ER, pre-secretion process (E.A. Fisher, 2004). Lipid peroxidation and oxidative stress mechanisms were implicated in the increased degradation and decreased secretion of apo... 

Mercury induces lipid peroxidation and oxidative stress and involves changes in the glutathione level (Fukino et al., 1984 Rana et al., 1995). 

Abuja, P.M. andAlbertini, R. (2001) Methods for monitoring oxidative stress, lipid peroxidation and oxidation resistance of lipoproteinOn. Chim. Acta, 306 1-17. 

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. 

Ellis et al. [72] recently studied the effects of short- and long-term vitamin C therapy in the patients with chronic heart failure (CHF). It was found that oxygen radical production and TBAR product formation were higher in patients with CHF than in control subjects. Both short-term (intravenous) and long-term (oral) vitamin C therapy exhibited favorable effects on the parameters of oxidative stress in patients the treatments decreased oxygen radical formation and the level of lipid peroxidation and improved flow-mediated dilation in brachial artery. However, there was no correlation between changes in endothelial function and oxidative stress. 

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