Prooxidant, vitamin

Bowry, V.W. and Stocker, R. (1993). Tocopherol-mediated peroxidation. The prooxidant effect of vitamin E on the radical-initiated oxidation of human low-density lipoprotein. J. Am. Chem. Soc. 115, 6029-6044. 

Edge, R and TG Truscott. 1997. Prooxidant and antioxidant reaction mechanisms of carotene and radical interactions with vitamins E and C. Nutrition 13(ll/12) 992-994. 

Vitamin C is also an antioxidant (supplements over 500 mg per day may have prooxidant effect). 

In contrast to transition metals iron and copper, which are well-known initiators of in vitro and in vivo lipid peroxidation (numerous examples of their prooxidant activities are cited throughout this book), the ability of nontransition metals to catalyze free radical-mediated processes seems to be impossible. Nonetheless, such a possibility is suggested by some authors. For example, it has been suggested that aluminum toxicity in human skin fibroblasts is a consequence of the enhancement of lipid peroxidation [74], In that work MDA formation was inhibited by SOD, catalase, and vitamins E and C. It is possible that in this case aluminum is an indirect prooxidant affecting some stages of free radical formation. 

The possible prooxidant effects of a major lipophilic antioxidant vitamin E (a-tocopherol) have already been discussed in Chapter 25. Yamashita et al. [82] showed that a-tocopherol induced extensive DNA damage including base modification and strand breakage in the... 

The mechanism of prooxidant effect of a-tocopherol in aqueous lipid dispersions such as LDLs has been studied [22], This so-called tocopherol-mediated peroxidation is considered in detail in Chapter 25, however, in this chapter we should like to return once more to the question of possible prooxidant activity of vitamin E. The antioxidant effect of a-tocopherol on lipid peroxidation including LDL oxidation is well established in both in vitro and in vivo systems (see, for example, Refs. [3,4] and many other references throughout this book). However, Ingold et al. [22] suggested that despite its undoubted high antioxidant efficiency in homogenous solution a-tocopherol can become a chain transfer agent in aqueous LDL... 

This mechanism is now considered to be of importance for the protection of LDL against oxidation stress, Chapter 25.) The antioxidant effect of ubiquinones on lipid peroxidation was first shown in 1980 [237]. In 1987 Solaini et al. [238] showed that the depletion of beef heart mitochondria from ubiquinone enhanced the iron adriamycin-initiated lipid peroxidation whereas the reincorporation of ubiquinone in mitochondria depressed lipid peroxidation. It was concluded that ubiquinone is able to protect mitochondria against the prooxidant effect of adriamycin. Inhibition of in vitro and in vivo liposomal, microsomal, and mitochondrial lipid peroxidation has also been shown in studies by Beyer [239] and Frei et al. [240]. Later on, it was suggested that ubihydroquinones inhibit lipid peroxidation only in cooperation with vitamin E [241]. However, simultaneous presence of ubihydroquinone and vitamin E apparently is not always necessary [242], although the synergistic interaction of these antioxidants may take place (see below). It has been shown that the enzymatic reduction of ubiquinones to ubihydroquinones is catalyzed by NADH-dependent plasma membrane reductase and NADPH-dependent cytosolic ubiquinone reductase [243,244]. 

Another important characteristic of oxidative stress in thalassemia is LDL oxidative modification. Livrea et al. [388] showed that the concentration of hydroperoxides in LDL of thalassemia patients was equal to 22.60+ 12.84 nmol/mg LDL protein compared to 6.25 +3.04 nmol/mg in control LDL. These authors proposed that the enhanced LDL oxidation in thalassemia was connected with the depletion of vitamin E in LDL. Interestingly, these findings contradict the suggestion about the prooxidant role of vitamin E (a-tocopherol) in LDL oxidation (Chapter 25). It was proposed that LDL oxidation could be the origin of atherogenetic risk in thalassemic patients. 

Finally it should be noted that similar to vitamin C (ascorbate) (08PNA11105), resveratrol in pharmacological concentrations and in the presence of Cu-ions can act as a prooxidant leading to cytotoxicity and apoptosis induction (09JMC1963, 01MI1111). 

To prevent this sun-induced cascade of oxidative injuries, topical preparations containing antioxidants have been developed in the past several decades. Initially, such antioxidants were added as stabilizers to various dermatologic and cosmetic preparations. In particular, lipophilic Vitamin E has been the favorite as a stabilizing agent. However, following oxidation, Vitamin E is degraded into particularly harmful prooxidative metabolites.177... 

Figure 4.5. Role of vitamin E as a chain-perpetuating prooxidant.

---