Hydroperoxide lipid, toxicity

Numerous studies have confirmed that lipid hydroperoxides are toxic, their products of decomposition even more so. For example, loss of -OH by cleavage of the relatively weak 0-0 bond gives rise to an alkoxy radical, which may decompose by breaking a neighboring C-C bond (j8-scission), forming an unsaturated aldehyde. 

When lipid hydroperoxides are ingested, they are rapidly degraded in the mucosal cells of the small intestine to various oxyacids that are rapidly further oxidized to CO2. There is no evidence for the absorption of unchanged hydroperoxides nor for their incorporation into tissue lipids. Although it is unlikely, therefore, that lipid hydroperoxides are toxic by... 

The health impairing and toxic elfects of oxidation of lipids are due to loss of vitamins, polyenoic fatty acids, and other nutritionally essential components formation of radicals, hydroperoxides, aldehydes, epoxides, dimers, and polymers and participation of the secondary products in initiation of oxidation of proteins and in the Maillard reaction. Dilferent oxysterols have been shown in vitro and in vivo to have atherogenic, mutagenic, carcinogenic, angiotoxic, and cytotoxic properties, as well as the ability to inhibit cholesterol synthesis (Tai et ah, 1999 Wpsowicz, 2002). 

Studies carried out with complete cells in vivo, cell membranes and other cell fractions point to the selective oxidation of phosphatidylserine (26) to a hydroperoxide (PS-OOH) on oxidative stress caused by toxic agents such as H2O2, t-BuOOH and cumyl hydroperoxide (27). Formation of PS-OOH is observed during apoptosis. These phenomena are important because of the cytotoxic effects of various peroxides used in commercial products coming into direct contact with the human body, as is the case of epidermal keratinocytes in contact with cosmetic formulations" ". The toxic effects of f-BuOOH are associated with vasoconstriction and damage to the vascular smooth muscles ". Global determination methods for primary lipid oxidation products are discussed in Section IV.B. 

A more recent view stresses the importance of lipid hydroperoxides in the dietary intake, for their possible toxic and pathogenic effects, as opposed to those produced in. ... 

Cells may show a low level of autofluorescence at 413 nm when irradiated at 324 nm. This fluorescence dramatically increases when d -parinaric acid (159) is incorporated into the cell membrane, either by intercalation or esteriflcation. Exposure to oxidation stress of cells enriched with the 159 fluorescent probe causes diminution of the fluorescence intensity and is directly correlated with formation of lipid hydroperoxides. Addition of antioxidants, such as Vitamin E (21), abates fluorescence diminution. A blanc run of cells enriched with 159 but not subjected to oxidation stress is necessary to follow the degradation of 159 when exposed to UV irradiation. This method was applied to track lipid oxidation during apoptosis and other phenomena, triggered by toxic compounds such as H2O2, f-BuOOH and cumyl hydroperoxide (27)"° 11,424... 

Decadienal has been reported as one of the most toxic lipid hydroperoxide breakdown products to ceUs . Besides l,Ai -etheno-2 -deoxyadenosine (edAdo) (156)... 

Helbock, H. J., Motchnik, P. A., and Ames, B. N. (1993), Toxic hydroperoxides in intravenous lipid emulsions used in preterm infants, Pediatrics, 91, 83-87. 

Lipid peroxidation (Figure 14.5) is the initiating reaction in a cascade of events, starting with the oxidation of unsaturated fatty acids to form lipid hydroperoxides, which then break down to yield a variety of end products, mainly aldehydes, which can go on to produce toxicity in distal tissues. For this reason cellular damage results not only from the breakdown of membranes such as those of the endoplasmic reticulum, mitochondria, and lysosomes but also from the production of reactive aldehydes that can travel to other tissues. It is now thought that many types of tissue injury, including inflammation, may involve lipid peroxidation. 

A comparison between the lung toxicity of methyl linoleate 9,10-ozonide and cumene hydroperoxide on rats showed that the former is 3 times more toxic than the latter <1994MI243>. It was also found that the ozonide did not enhance lipid peroxidation. Glutathione and vitamin E protected rats against the effect of the ozonide. 

The Toxicity of Lipid Hydroperoxides and Their Decomposition Products... 

Firstly, I will discuss recent evidence supporting the hypothesis that free radicals contribute to important chronic diseases in man and exert an important life-shortening effect. Secondly, I will review data on the toxicity of lipid hydroperoxides and their decomposition products, since lipid hydroperoxides can be a source of free radicals in vivo. And lastly, I will review a system under study in our laboratory in which quantitative data on lipid peroxidation and antioxidants is being obtained using linoleic acid in SDS micelles. 

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