Ascorbic acid with peroxidized lipids

It has been known for some years that ascorbic acid stimulates collagen gene expression and collagen synthesis in cultured fibroblasts [83] and, more recently, it has become clear that this effect is related to the ability of ascorbic acid to induce lipid peroxidation in the presence of iron ions, with the formation of reactive aldehydes [84],... 

The concentration of ascorbate in the human plasma is 25 pM and above. Cells take up ascorbate by a Na -coupled uptake mechanism against a concentration gradient. A marked stereo-selectivity for L-ascorbic acid relative to D-isoascorbic acid in their cellular transport has been shown by Franceschi et al. [12]. The same transport is also important in the intestine. The nutritional supply of ascorbic acid is the only source for this vitamin in humans, primates, and guinea pigs. Other mammals are able to produce ascorbic acid. There exists sufficient evidence for an active role of ascorbate as an antioxidant in vivo. Decreased ascorbic acid will increase lipid peroxidation and decrease vitamin E and is connected with oxidative DNA damage. The supply of ascorbate in some cases will reduce the amount of oxidative damage in diseases that... 

Treatment of 5,6-0-isopropylidene-L-ascorbic acid with alkyl halides and NaHCOs in DMSO gave alkylation only at 0-3 the products were then hydrolysed to give 3-0-alkyl-ascorbic acids as free radical scavengers.78 The crown ether type of derivatives (68) of isopropylidene-L-ascorbic acid could be made by interaction with the appropriate ditosylate and K2CO3 in DMF the reaction was unsuccessful in the case of (68, n=2).79 The mechanism by which 3-0-dodecylcarboxymethyl-ascorbic acid inhibits lipid peroxidation. 

Antioxidant capacities of common individual curcuminoids were determined in vitro by phosphomolybdenum and linoleic acid peroxidation methods. Antioxidant capacities expressed as ascorbic acid equivalents (pmol/g) were 3099 for curcumin, 2833 for demethoxycurcumin, and 2677 for bisdemethoxycurcumin at concentrations of 50 ppm. The same order of antioxidant activity (curcumin > demethoxycurcumin > bisdemethoxycurcumin) was observed when compared with BHT (buty-lated hydroxyl toluene) in linoleic peroxidation tests. The antioxidant activity of curcumin in the presence of ethyl linoleate was demonstrated and six reaction products were identified and structurally characterized. The mechanism proposed for this activity consisted of an oxidative coupling reaction at the 3 position of the curcumin with the lipid and a subsequent intramolecular Diels-Alder reaction. ... 

Kaneko et al. (1993) have described a group of lipophilic ascorbic-acid analogues that have been studied in cultured human umbilical vein endothelial cells that were first incubated with test drug and then exposed to lipid hydroperoxides. Although ascorbate itself did not protect the endothelial cells, derivatives like CV3611 protected. Pretreatment was necessary. CV3611 was synergistic with vitamin E. The authors concluded that these lipophilic antioxidants incorporate into endothelial cell membranes where they are effective inhibitors of lipid peroxidation. In contrast, lipophobic antioxidants were not effective in their hands (Kaneko et al., 1993). 

Wrona, M, Rozanowska, M, and Sarna, T, 2004. Zeaxanthin in combination with ascorbic acid or alpha-tocopherol protects ARPE-19 cells against photosensitized peroxidation of lipids. Free Radic Biol Med 36, 1094-1101. 

Nitrosoarenes are readily formed by the oxidation of primary N-hydroxy arylamines and several mechanisms appear to be involved. These include 1) the metal-catalyzed oxidation/reduction to nitrosoarenes, azoxyarenes and arylamines (144) 2) the 02-dependent, metal-catalyzed oxidation to nitrosoarenes (145) 3) the 02-dependent, hemoglobin-mediated co-oxidation to nitrosoarenes and methe-moglobin (146) and 4) the 0 2-dependent conversion of N-hydroxy arylamines to nitrosoarenes, nitrosophenols and nitroarenes (147,148). Each of these processes can involve intermediate nitroxide radicals, superoxide anion radicals, hydrogen peroxide and hydroxyl radicals, all of which have been observed in model systems (149,151). Although these radicals are electrophilic and have been suggested to result in DNA damage (151,152), a causal relationship has not yet been established. Nitrosoarenes, on the other hand, are readily formed in in vitro metabolic incubations (2,153) and have been shown to react covalently with lipids (154), proteins (28,155) and GSH (17,156-159). Nitrosoarenes are also readily reduced to N-hydroxy arylamines by ascorbic acid (17,160) and by reduced pyridine nucleotides (9,161). 

Placental tissue incubated for as long as 24 h in media containing 145 mg Ni/L MONKEYS When compared to controls, treated tissues had increased permeability, lipid peroxidation, and nickel concentration over time. Treatment with ascorbic acid or zinc decreased nickel-induced placental lipid peroxidation and permeability, but had no effect on nickel tissue concentrations 43... 

A highly selective method for determination of lipid hydroperoxides is based on the oxidation of ferrocenecarboxylic acid (201) to the corresponding ferrocenium compound (202), as shown in equation 69, followed by amperometric reduction of this complex with a GCE set at —100 mV vs. SCSE, in phosphate buffer at pH 5.5. The method is insensitive to dissolved oxygen and no interference is observed, either from reductors such as ascorbic acid (22) or uric acid (29) nor from other hydroperoxides such as H2O2 and f-BuOOH at the 1 xM concentration level. At this concentration, a slight interference is observed for cumyl hydroperoxide (27) and 2-butanone peroxide (46 4- 47). The LOD... 

Since ascorbate reduces photooxidation of lipid emulsions and multivitamin preparations (see Figure 4) [19], Lavoie et al. [34] studied the formation of oxidative by-products of vitamin C in multivitamins exposed to light. They found that the loss of ascorbic acid in photoexposed multivitamin preparations was associated with the generation of products other than dehydroascorbate and 2,3-diketogulonic acid, which are the usual products of vitamin C oxidation. The authors showed that hydrogen peroxide at concentrations found in TPN solutions induced the transformation of dehydroascorbate into new, biologically active compounds that had the potential to affect lipid metabolism. They believe that these species have peroxide and aldehyde functions [35]. 

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