Effects of Antioxidants

A number of studies have demonstrated protection against ethanol-induced gastric mucosal damage with several antioxidants, including SOD, catalase, allopurinol, DMSO, thiourea, dimethylthiourea, propylgallate and sulphydryl-containing substances, such as cysteine and 

Gastric mucosal injury induced by non-steroidal antiinflammatory drugs such as aspirin and indomethacin has also been extensively studied, again with somewhat conflicting results. Several studies have shown a protective effect of SOD, catalase, hydroxyurea and desferrioxamine (Takeuchi et al., 1991a Vaananen et al., 1991 Naito et al., 1992). Del Soldato etal. (1985) also found aminopy-rine, thiourea and its derivative, MK 447, and SAZ to be protective. Allopurinol has been shown to be both protective (Takeuchi etal., 1991a) and ineffective (Vaananen etal., 1991). 

Salim (1992d) has performed several studies using reser-pine to produce a chronic model of peptic ulceration in rats. Administration of allopurinol, DMSO, cysteine or methionine-S-methylsulphonium chloride protected against injury. In addition allopurinol and DMSO were found to stimulate healing in this model. In an acute model of duodenal ulceration induced by pentagastrin and carbachol allopurinol, DMSO, cysteine or methionine-S-methylsulphonium chloride all protected against injury. 

There is now a considerable body of evidence to suggest that ROMs are involved in the pathophysiology of gastroduodenal damage. However, we await confirmation that antioxidants, such as allopurinol, are beneficial in human peptic ulcer disease. Salim (1990c) found 

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There are numerous reports of the effects of antioxidant vitamins on transformation. Vitamin C suppresses x-ray-induced transformation when CSHlOTy cells are treated daily for one week following irradiation (97), suppresses transformation by y-rays or neutrons, and prevents the promotion of radiation-induced transformation by 12-0-tetradecanoylphorbol 13-acetate (TPA), but has no effect on cell survival (98). In these studies, the continuous presence of vitamin C for a critical period appears to be necessary for suppression of transformation. Vitamin C may act on the promotion stage of... 

The effectiveness of antioxidants as preservatives for fats and oils is evaluated by determining the rate of peroxide development using the Active Oxygen Method (AOM) (29). The development of a rancid odor is used to evaluate the stabiUty of food items (Schaal Oven StabiUty test) (30). 

Figure J0.J2. Oxidation of polyethylene in air at 105 C. Effect of antioxidant concentration (/V -diphenyl-p-phenyienediamine). A, blank. B, 50ppm. C, 100 ppm. D, 500ppm. E, 1000ppm...

The use of antioxidants has already been generally described in Chapter 7. The mechanism of oxidation and the effect of antioxidants are altered by the sulphide cross-links and other structures present in the vulcanisate. There are indeed grounds for arguing that a correct choice of curing system is more important than the decision whether or not to incorporate an antioxidant. 

The effectiveness of antioxidants depends not only on their intrinsic activity but also on their physical retention in the polymer. Migration of antioxidants into the sur-... 

The effect of antioxidants such as hindered phenohcs, secondary amine, and thioester on the radiation cross-linking efficiency of LDPE has been reported [260]. Amount of cross-linking at a given dose decreases with aU the antioxidants, the thioester being the most effective. IR absorption spectroscopy has been used to demonstrate dose-rate dependence of trani -vinylene unsaturation in irradiated Marlex 50 PE [261]. When the irradiated polymer is stored in vacuum a decrease is observed in trani-vinylene absorbance over a period of several weeks. After high dose-rate irradiation the decay is preceded by an initial increase. These phenomena have been ascribed to the reaction of trapped radicals. 

Many epidemiological studies have analyzed the correlations between different carotenoids and the various forms of cancer and a lot of conclusions converge toward protective effects of carotenoids. Many studies were carried out with (i-carotene. The SUVIMAX study, a primary intervention trial of the health effects of antioxidant vitamins and minerals, revealed that a supplementation of p-carotene (6 mg/day) was inversely correlated with total cancer risk. Intervention studies investigating the association between carotenoids and different types of cancers and cardiovascular diseases are reported in Table 3.1.2 and Table 3.1.3. 

Hercberg, S. et al.. The SU.VI.MAX Study a randomized, placebo-controlled trial of the health effects of antioxidant vitamins and minerals. Arch. Intern. Med., 164, 2335, 2004. 

Kim, H.S. and Lee, B.M., Protective effects of antioxidant supplementation on plasma lipid peroxidation in smokers, J. Toxicol. Environ. Health A, 63, 583, 2001. Gaziano, J.M. et al.. Supplementation with beta-carotene in vivo and in vitro does not inhibit low density lipoprotein oxidation. Atherosclerosis, 112, 187, 1995. Sutherland, W.H.F. et al.. Supplementation with tomato juice increases plasma lycopene but does not alter susceptibility to oxidation of low-density lipoproteins from renal transplant recipients, Clin. Nephrol, 52, 30, 1999. 

At the present time it is difficult to single out any one factor that could be held ultimately responsible for cell death after cerebral ischaemia. Recent studies, however, have provided us with sufficient evidence to conclude that free radical damage is at least one component in a chain of events that leads to cell death in ischaemia/reperfiision injury. As noted earlier in this review, much of the evidence for free radicals in the brain and the sources of free radicals come from studies in animals subjected to cerebral ischaemia. Perhaps the best evidence for a role for free radicals or reactive oxygen species in cerebral ischaemia is derived from studies that demonstrate protective effects of antioxidants. Antioxidants and inhibitors of lipid peroxidation have been shown to have profound protective effects in models of cerebral ischaemia. Details of some of these studies will be mentioned later. Several reviews have been written on the role of oxygen radicals in cerebral ischaemia (Braughler and HaU, 1989 Hall and Btaughler, 1989 Kontos, 1989 Floyd, 1990 Nelson ef /., 1992 Panetta and Clemens, 1993). 

Dillard, C.J., Downey, J.E. and Tappel, A.L. (1984). Effects of antioxidants on lipid peroxidation in iron-loaded rats. Lipids 19, 127-133. 

Niederau, C., Niederau, M., Borchard, F., Ude, K., Luthen, R., Strohmeyer, G., Ferrell, L.D. and Grendell, J.H. (1992). Effects of antioxidants and fiee radicals scavengers in three different models of acute pancreatitis. Pancreas 7, 486—496. 

McArdle, A., Edwards, R.H.T. and Jackson, M.J. (1994). The effects of antioxidants on skeletal muscle fatigue. Proceedings of the 4th International Congress on Trace Elements in Medicine and Biology (in press). 

Three factors determine the effectiveness of antioxidants in polymers, namely (i) intrinsic molar activity (ii) substantivity in the polymer and (iii) solubility in the polymer. Multifunctional AOs combine multiple functions in one molecule. Sterically hindered amine stabilisers (HAS), such as Chimassorb 944, Tinuvin 622 and Tinuvin 783 are prime examples. 

Table 4 The effect of antioxidants on induction time of oxidation of polypropylene determined at 150°C from chemiluminescence measurements...

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