These observations suggest that amiodarone in vitro and in vivo generates free radicals that may play a role in the pathogenesis of amiodarone toxicity beside other well-established mechanisms, and antioxidants may have a partial protective effect against amiodarone toxicity.
In blood samples of 54 obese persons (13 men, 41 women) some lipid components, malondialdehyde (MDA), and the activities of free radical protecting enzymes superoxide-dismutase (SOD) and glutathione-peroxidase (GSHpx), were determined before and after a seven-day slimming diet of 2.1 MJ/day. Body weight, triglycerides, HDL-cholesterol, and HDL-3-cholesterol all decreased, total cholesterol increased after the seven days hospitalization. After continuing the slimming diet (5.0-6.3 MJ/day) at home, HDL-2-cholesterol increased and total cholesterol returned to the initial value after three months. MDA decreased in the groups of hyperlipoproteinemia II/a and II/b and also in the group with high cholesterol and triglyceride levels (above 5.7 and 2.7 mmol/l). Correlation coefficients refer to the dominant role of high TG in the intensity of lipid peroxidation. The activity of SOD fell after the slimming, independent of lipid parameters. GSHpx activity remained unchanged except a drop in the male participants having high cholesterol levels. The behavior of the free radical protecting enzymes needs further examination.
Groups of adult Wistar male and female rats were fed isoenergetically for a three and a six weeks period either with synthetic lipogenic diet containing 5% and 20% fat mixtures (in which sunflower oil and lard were blended according to the ratio of 35:65) or with the same synthetic diet containing the mixture of sunflower oil and interesterified lard in a similar ratio. A control group received a normal diet for 6 weeks, whereas one of the experimental groups (fed with the 20% fat mixture in the lipogenic diet for 6 weeks) was given the normal diet for an additional two weeks period. After the feeding periods had been completed serum HDL-C levels and the total lipid, triglyceride, total cholesterol, free fatty acid levels were determined in serum and liver. The distribution of fatty acids in liver and heart muscle was also evaluated. In comparison to the control values it has been found: 1. Consumption of the lipogenic diet which is known to increase the serum total lipid and total cholesterol content induced in male rats a smaller augmentation in these indices when consuming the 20% fat mixture with a P/S ratio approaching the ideal 1 values, than in case of a 5% fat mixture consumption. In case of female rats, considerable increases of the serum values, could be observed at both fat consumption levels. The serum triglyceride and HDL-C contents decreased for all experimental groups. 2. The total lipid and triglyceride content of the liver increased in a high degree, the fatty liver syndrome was developed--more rapidly in males than in females. The total lipid, triglyceride and total cholesterol contents of the liver of male rats exceeded those of females by 15-30%. 3. The interesterification of the lard component of fat mixture resulted in lipid indices similar to those without interesterification, or in certain cases, they were found to be even slightly more favourable, i.e. the biological effect of the technological change proved to be adequate. 4. After a two weeks regeneration period the serum values of the male rats approached closer the normal control values than those of the females which were decreasing from a very high level but the degree of decrease was greater for them than for the male rats. The lipid content of the liver showed similar values.(ABSTRACT TRUNCATED AT 400 WORDS)
Adult male and female Wistar rats were fed isoenergetically for a 6 week period with a lipogenic diet containing a 20% fat mixture which caused fat-metabolism disturbance. One group consumed the mixture of sunflower oil and lard in a ratio of 0.91 P/S, the other group the interesterified form of the same mixture. The linoleic acid content of the mixtures was 0.4%. The fat mixture of the third group's diet was adjusted with soya oil to a linoleic-acid content of 0.8%. The results were compared to the control data obtained in rats fed with a normal diet. The changes in various lipid indices of the serum and the liver and the levels of some metals in the liver were analysed. It was found that; in comparison to the control on the effect of the lipogenic diet the total lipid and cholesterol contents of the serum increased significantly in all groups (a significantly higher value being observed for the females than for the males) whereas the HDL-C content decreased.(ABSTRACT TRUNCATED AT 250 WORDS)
The non-toxic and water soluble dihydroquinoline type antioxidants: CH 402 (Na-2,2-dimethyl-1,2-dihydroquinoline-4-yl methane sulphonate) and MTDQ-DA (6,6-methylene bis 2,2-dimethyl-4-methane sulphonic acid: Na-1,2-dihydroquinoline) were studied in various in vitro tests in which oxygen free radicals were generated. Both compounds were shown to scavenge superoxide radical anions O2- produced in aqueous solution by pulse radiolysis with rate constants k (O2- + MTDQ-DA) = 4.10(8) dm3 mol-1 s-1 and k (O2- + CH 402) = 1.5.10(7) dm3 mol-1 s-1. CH 402 and MTDQ-DA reduced the H2O2 produced in the glucose-glucose oxidase reaction, which was detected by the luminol + hemin reaction with a chemiluminometric method. The dihydroquinoline type substrates inhibited the NADPH-induced and Fe3+ - stimulated lipid peroxidation and the ascorbic acid-induced non-enzymatic peroxidation pathways in microsomal fractions of rat and mouse liver.
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