No abstract

The role of free radicals and lipid peroxidation is reviewed with regard to the aging process. Free radicals are produced during mitochondrial respiration, during the autooxidation of a variety of biological molecules and chemicals, during irradiation damage, and are found as environmental pollutants. Free radicals induce lipid peroxidation which results in membrane damage, increased disulfide/sulfhydryl ratios, and accumulation of aging pigments. Superoxide dismutase, glutathione peroxidase, vitamin E, vitamin C, and selenium are of importance with respect to free radical and lipid peroxide quenching. During aging, the levels of vitamin C appear to decline in the human, guinea pig, and the mouse. Synthetic antioxidants, added to the diets of mice, have been noted to extend the lifespan and mean half-survivale times.

Rats were fed for 5 wk 10% (wt/wt) menhaden oil (MO) or a 10% corn oil-lard (COL) mixture (1:1) in diets with a low vitamin E content (less than or equal to 5 mg/kg) or supplemented with d-alpha-tocopheryl succinate to a total of 30 or 150 mg per kg. Thiobarbituric acid-reactive substances (TBARS), conjugated dienes (CD), hexanal and total volatiles (TOV) were measured in tissue homogenates incubated at 37 degrees C for 1 h in the absence (uninduced) and presence of 15 microM ferrous sulfate (induced). The fatty acid composition of liver and kidney reflected that of dietary lipids. For uninduced peroxidation, there was in general a significant inverse correlation of TBARS, CD and TOV with the log of dietary vitamin E content for liver and kidney from rats fed either lipid. For induced peroxidation, the inverse correlation was significant for liver, but not for kidney, from rats fed either lipid. The correlation was generally higher for liver and kidney from rats fed COL than for tissues from rats fed MO. Vitamin E was thus a more effective antioxidant for liver than for kidney regardless of the dietary lipid, and for liver and kidney from rats fed COL than from rats fed MO. Dietary MO enhanced tissue susceptibility to both peroxidation systems. A simulation model developed to mimic the experiments showed good correlations between experimental data and simulated values.

A tissue slice model was employed to assess the effects of dietary antioxidant supplements on lipid peroxidation. In one experiment, rats were fed diets containing, either alone or in combination, vitamin E, selenium, beta-carotene or coenzyme Q10 for 42 d, and the extent of spontaneous and induced lipid peroxidation was determined by release of thiobarbituric acid-reactive substances (TBARS) into the medium. Vitamin E exhibited the greatest protection against lipid peroxidation in liver, heart and spleen; in kidney, selenium was most protective. Coenzyme Q10 was active against lipid peroxidation induced by tertbutyl hydroperoxide (t-BHP). In a second experiment, rats were fed diets containing varying amounts of vitamin E, selenium, beta-carotene and coenzyme Q10 for 30 d. Spontaneous lipid peroxidation in liver, kidney and heart decreased with increasing levels of dietary antioxidants. With increasing amounts of antioxidants, there was a diminution in TBARS released by liver and kidney slices incubated with t-BHP; in heart, only the highest levels of antioxidants significantly decreased production of TBARS. Inverse correlations between dietary vitamin E and TBARS, tissue vitamin E and TBARS, and tissue selenium-glutathione peroxidase and TBARS were highly significant. The procedure used here can evaluate dietary supplements that may find practical applications in decreasing the oxidant radical portion of disease processes.

Rats were fed for 5 weeks either 10% (w/w) menhaden oil (MO) or a 10% corn oil-lard (COL) mixture (1:1) in diets with less than or equal to 5 IU or less than or equal to 2 IU/kg vitamin E, respectively, or the same diets supplemented with d-alpha-tocopheryl succinate to a total of 35 and 180 IU vitamin E/kg, respectively. Slices of liver and heart from these rats were used to study lipid peroxidation in vitro. Thiobarbituric acid-reactive substances (TBARS) were measured in the medium after incubation of the slices at 37 degrees C for 1 hr in the absence (uninduced) and presence of 0.5 mM tert-butyl hydroperoxide (induced). The release of TBARS from slices of heart and liver from rats fed either lipid decreased with increasing levels of dietary vitamin E. At the same level of dietary vitamin E, TBARS release was greater for slices of liver and heart from the MO-fed rats than from the COL-fed rats. Application of the TBARS data to a model simulating the experimental conditions showed a good correlation (r = 0.95, p less than 0.001) between experimental and simulated values. Of the 16:0-22:6 fatty acids measured in liver from MO-fed rats, 15.4% was n-6 fatty acids and 29.9% was n-3 fatty acids; in liver from COL-fed rats, the respective values were 37.4% and 3.7%. Liver and kidney vitamin E levels were unaffected by the dietary lipid.(ABSTRACT TRUNCATED AT 250 WORDS)