Effect of antioxidants on lipid peroxidation in iron‐loaded rats

Abstract

Indirect evidence has suggested that lipid peroxidation is associated with iron overload in vivo. As a measure of lipid peroxidation, pentane expired in the breath of rats loaded with an accumulated dose of either 100 mg or 186-200 mg of iron injected intraperitoneally as iron dextran was measured over a 7 to 8 week period, and the effect on pentane production of feeding antioxidant-supplemented diets was determined. By the seventh week of feeding the diets, rats fed 0.3% L-ascorbic acid produced 17% less (P = 0.03) pentane than did rats fed the basal antioxidant-deficient diet, whereas rats fed 0.004% dl-alpha-tocopherol acetate produced 92% less (P less than 0.001). After being fed the basal diet for 7 weeks, iron-loaded rats produced 76 +/- 9 pmol pentane/100 g body wt/min. When synthetic antioxidants were added to the diet at a concentration of 0.25%, the order of effectiveness in decreasing pentane production after 1 week was: N,N'-diphenyl-p-phenylenediamine greater than ethoxyquin greater than butylated hydroxyanisole greater than butylated hydroxytoluene greater than propyl gallate approximately equal to no antioxidant. After removal of either ethoxyquin or N,N'-diphenyl-p-phenylenediamine from the diets for 1 week, pentane production increased to a high level. The total amount of lipid soluble fluorophores in individual spleens of rats fed N,N'-diphenyl-p-phenylenediamine, ethoxyquin, dl-alpha- tocopherol acetate, ascorbic acid and no antioxidant were correlated significantly with the corresponding total integrated amount of pentane produced by the individual rats over the 7 to 8 week period. This study has provided some of the most direct evidence to date that lipid peroxidation is associated with iron overload in vivo.

Iron-Induced Myocardial and Hepatic Lysosomal Abnormalities in the Guinea Pig

“…Demonstration of iron-enhanced lipid peroxidation in this report was consistent with numerous studies (2,4,5,9,10,17,18). Findings of a previous in vifro investigation indicated that incubation of isolated hepatic lysosomes in the presence of iron rapidly produced maximal levels of lysosomal lipid peroxidation with subsequent increase in lysosomal fragility (1 7, 18).…”

Malondialdehyde and 4-hydroxynonenal protein adducts in plasma and liver of rats with iron overload.

“…Lipid peroxidation has been shown to occur in rats loaded with iron by either multiple injections of an iron-chelate (6,8,10,38,39) or through dietary methods (6,7,11), and this has been demonstrated in whole animals (10,39), in the liver (38), and in subcellular organelles (6,7,8,11). In these reports, kD -200 several methods of detecting lipid peroxidation were used, including the measurement of ethane and pentane (10,39), conjugated dienes (6, 7, 1 1), and TBARS (8,38).…”

“…In these reports, kD -200 several methods of detecting lipid peroxidation were used, including the measurement of ethane and pentane (10,39), conjugated dienes (6, 7, 1 1), and TBARS (8,38). In cell-free systems, highly reactive aldehydes, formed as a result of lipid peroxidation, can bind to proteins and inhibit their function (40).…”

Synergistic Action of Vitamin E and Vitamin C in Vivo Using a New Mutant of Wistar-Strain Rats, ODS, Unable to Synthesize Vitamin C.

“…But, with regard to in vivo conditions , clear evidence has not yet been established. A few papers suggest some interrela tionship of vitamins E and C in vivo, but they involve only indirect evidence in rats (7)(8)(9)(10), guinea pigs (11)(12)(13)(14)(15), and humans (16,17).…”