The effectiveness of rabbit Interferon In suppressing atherosclerosis was evaluated In rabbits fed a diet containing 1 % cholesterol. Ten male New Zealand White rabbits received Intramuscular Injections of 1 million units of Interferon twice a week, while a control group of 10 rabbits received Injections of buffer. Both groups had average serum cholesterol levels of over 2000 mg/dl during the 8-week experimental period. Interferon treatment resulted In no significant hypolipidemlc effect or changes In llpoproteln composition. Atherosclerotic lesions In aortas were quantified both macroscopically and microscopically. Interferon treatment decreased the grossly visible lesion area significantly from 25±4% to 8 ± 1 % (mean±SEM, p<0.005) compared to the untreated group. Microscopic analysis of serial cross-sections of aortic segments revealed significant (p<0.01) reductions In both lesion size and frequency in the Interferon-treated group. Electron microscopy also showed that Interferon treatment reduced the pathological effects of cholesterol feeding. Tissue analysis showed that total aortic cholesterol was reduced by 28% by Interferon treatment, while the aortic phosphollpid concentration was Increased by 25%. The possibility exists that the interferon preparation used contained other biological response modifiers and that the observed effects may be totally unrelated with Interferon. These results suggest that the mechanism of atherosclerosis suppression In these cholesterol-fed rabbits Is not related to the lowering of serum cholesterol but may be associated with Inhibition of lesion Initiation. A therosclerotic lesions develop as the result of the interplay between the multiple risk factors associated with Increased incidence of atherosclerosis, the cells of the arterial wall, and the circulating blood cells. 1 Increased understanding of these interactions is critical to developing new approaches to prevention and therapy.Since the discovery of interferon as an antiviral agent in 1957, interest has grown in its nonantiviral activities, 2 particularly in its use in cancer therapy. 3 Interferons exhibit a wide range of effects, each depending on the type of interferon and the nature and state of differentiation of the target cell. Interferons are involved in the inhibition of cell growth and proliferation, regulation of the expression of specific genes, modulation of cell differentiation, and activation of certain cell types in the immune system, for example, macrophages and natural killer cells. 4 The Interferon inducers, polyinoslnic-polycytidylic acid and 2-amino-5-bromo-6-phenyl-4(3H)-pyrimidinone (U-54,461), have been shown to suppress atherosclerosis in rabbits. 5 It is important to establish whether the Received October 28,1988; revision accepted October 20,1989. anti-atherogenic effect is a direct effect of these drugs or is mediated by interferon. The purpose of the present study was to evaluate the anti-atherogenic effectiveness of the administration of purified rabbit interferon in the cholesterol-fe...
The effects of two chemically different interferon inducers on the suppression of atherosclerosis were studied in rabbits fed an atherogenic chow diet. One group (10 rabbits per group) was fed normal rabbit chow, and three groups were fed an atherogenic chow. One of the latter groups received the atherogenic feeding alone; the other two were treated with either polyinosinic-polycytidylic acid (poly I:C) or 2-amino-5-bromo-6-phenyl-4-pyrimidinone (ABPP). Neither of the drugs reduced significantly the hypercholesterolemia induced by the feeding. However, both poly I:C and ABPP treatment significantly reduced the percent area of the aortic intimal surface lesions, stained for lipid with Sudan IV, compared with that in untreated rabbits fed atherogenic chow. Microscopic sections of typical aortic plaques showed that both drug treatments significantly reduced the size and number of intimal lipid deposits compared with those observed in the aortas of untreated animals. Chemical analysis for cholesterol and collagen content revealed that interferon-inducing agents significantly reduced cholesterol deposits in the aorta, with little effect on fibrous protein deposition. The results indicate that two unrelated interferon-inducing drugs suppressed atherogenesis without reducing serum cholesterol and low density lipoprotein levels. Whether the protection against atherosclerosis is exerted by endogenous interferon production remains to be determined.
The nucleophile 4‐(p‐nitrobenzyl)pyridine was allowed to react with four carcinogenic alkylating agents, chloromethyl methyl ether, bis(chloromethyl) ether, glycol sulfate and propane sultone, one carcinogenic acylating agent, N,N‐dimethylcarbamyl chloride, and one noncarcinogenic electrophile, perchlorocyclobutenone. The structures of the major products formed, which are substituted pyridinium salts or 1,4‐dihydropyridines, were determined.
The effect of 8 weeks of daily oral fish oil supplementation in a dose of 3 to 8 g/d on serum lipid levels was studied in 16 patients, 7 to 8 years of age, who had end-stage renal disease and were receiving renal replacement therapy. Fasting serum cholesterol (CHOL), triglyceride (TG) levels, and lipoprotein profiles were measured before therapy, 8 weeks after fish oil supplementation, and 4 weeks after its cessation. During 8 weeks of treatment the mean serum CHOL level did not change. The mean serum TG level, however, decreased significantly (P < .01) from 236 ± 31 mg/dL to 171 ± 21 mg/dL (27.5%). Four weeks after treatment was stopped, the mean serum TG level returned to a value not significantly different from the pretreatment level (208 ± 30 mg/dL). In a subgroup of 11 excessively hyperlipidemic patients, with serum CHOL and TG levels ≥50% of the 90th percentile for age and sex, the mean serum TG level decreased even more (30.8%), from 286 ± 35 mg/dL to 198 ± 24 mg/dL (P < .01), and the mean CHOL/high-density lipoprotein CHOL ratio decreased from 8.4 ± 1.2 to 7.4 ± 1.3 (P < .05). Blood pressure and platelet counts remained stable during the entire study period. Side effects of the treatment were minimal. These results show that dietary fish oil supplementation reduces serum TG levels in young patients receiving renal replacement therapy and improves their "atherogenic" serum lipoprotein profile.
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