Search

Anti-elastin antibodies which seem to play an important role in atherogenesis were studied in serum of rabbits fed with a cholesterol-rich diet using the dot-immunobinding assay. These antibodies appeared only in rabbits of the experimental group after the sixth week of the experiment and a progressive rise in their titer was observed. The concentration of total serum cholesterol and the elastase-like activity in aorta which were determined additionally showed a statistically significant increase of both analyzed parameters in animals from the experimental group when compared to the controls. Anti-elastin antibodies seem to reflect an increased elastin turnover during the induction of experimental atherosclerosis.

Murine fibroblasts cultured in vitro were treated with hydrazinophthalazine drugs inducing the lupus erythematosus-like syndrome. Collagenase enzyme activity in the growth medium was found to be increased 3-fold by hydralazine and 1.8-fold by binazine, as compared to the control cultures. The enhanced level of collagenolytic activity points to the metabolic changes in the connective tissue in response to hydrazinophtalazines.

A drug-induced collagen-like syndrome was produced in rats by hydralazine administration for 8, 9 and 10 months. The hyaluronic acid content and the hyaluronidase activity in liver and spleen were studied. A decrease in the hyaluronic acid amount was accompanied by an enhanced activity of hyaluronidase in both tissues. The results provide evidence for metabolic disturbances of glycosaminoglycans in the connective tissue in the collagen disease-like syndrome.

Variations in superoxide dismutase, catalase and glutathione peroxidase activity were studied in fibroblasts cultured in the presence of hydralazine, a drug known to be an inducer of the so-called collagen-like syndrome. The results demonstrated that both superoxide dismutase and catalase undergo a marked decrease in their activity, whereas glutathione peroxidase manifests a significant increase in its activity after treatment with hydralazine as compared to control cell cultures. Also the lipid peroxide concentration as expressed by the malondialdehyde amount was estimated in the above cultures. The altered antioxidant enzyme activity and the presence of byproducts of free radical damage support the possibility that the action of hydralazine leading to the pathogenesis of collagen disease-like syndrome involves an abnormal free-radical metabolism.

Cardiomyopathy was produced by isoprenaline injections to healthy and hydrazinophthalazine-treated rats. The elastin content in the heart muscle and the aortic wall as well as the level of serum elastolytic activity were determined. An increase of elastin content in both tissues was found, and its progress was concomitant with the development of isoprenaline injury. It was also found that the elastolytic activity increased on the second day after the last isoprenaline injection, and on the seventh day of the experiment it began to decrease. Changes in hydrazinophthalazine-treated rats after dosing them with isoprenaline had a similar tendency but they were significantly lower than those found in healthy animals receiving isoprenaline only.

Ionic fluoride is taken up by rabbit synovial fibroblasts in culture. The uptake was accompanied by an increased production of latent collagenase, and decreased activity of 5'-nucleotidase.

Changes in skin collagen structure were studied after i.p. injection of phenylalanine mustard to rats. First order amino groups of lysine and arginine reacted with phenylalanine mustard, as stated potentiometrically. Bacterial collagenase was used to solubilize the skin collagen, and the aldehyde content of this material was measured using N-methyl benzothiazolone hydrazone. The aldehyde content was decreased in the collagen from rats skin after phenylalanine mustard injection. The observed changes in collagen may be analogous to the effect of aging, wherein collagen cross-linking is strengthened although qualitative changes in cross-linking may lower the measurable aldehydes.