Influence of various drugs on the tissue permeability. 2

Abstract

In order to elucidate the mechanism of the increase of inflamed dermal tissue permeability in filter paper-implanted rats and the inhibitory effect of anti-inflammatory drugs, the author attempted a determination of the changes in mucopolysaccharase (M) activities in inflamed tissue and the effect of anti-inflammatory drugs. Enzymes determined were β-glucuronidase (β-G), N-acetyl-β-glucosaminidase (NA-β-G) and lysozyme (LZ). 1) When inflamed tissue was divided into skin side upper filter paper and the under muscle one, β-G and NA-β-G activities in both tissues elevated slowly until day 7, thereafter rapidly and markedly. LZ activity elevated remarkably, especially on the muscle side after day 10. 2) From 7 to day 25, the inflamed region was divided further into exudate, granuloma, skin and muscle and these three enzyme activities changed with a similar pattern in each region. These enzyme activities in exudate continued to elevate even after day 15, while those in granuloma, skin and muscle reached a maximum at days 15, 10 and 7 respectively and thereafter declined. 3) The drug effect on M activities in inflamed tissues (skin and muscle sides) 3 days after implantation was examined by a daily, oral administration for 3 days. The elevations of β-G and NA-β-G activities in inflamed tissues were inhibited remarkable by prednisolone, dexamethasone, indomethacin and phenylbutazone. Bucolome, flufenamic acid and benzyd-amine HCl showed only a weak inhibitory effect. All non-steroids tested remarkably inhibited the elevation of LZ activity in inflamed tissues, whereas steroids exibited only a weak inhibitory effect. 4) The drug effect on M activities in exudate and inflamed tissues (granuloma, skin and muscle) 10 days after implantation was tested by an oral, daily administration for 10 days. β-G and NA-β-G activities in exudate and granuloma were inhibited significantly by prednisolone, dexamethasone and indomethacin, while LZ activity was inhibited in both regions by bucolome, benzydamine HCl and indomethacin. These three enzyme activities in skin and muscle were inhibited significantly by almost all drugs tested. 5) From these results, the increase of inflamed dermal tissue permeability could by partially due to the elevated M activities. It can be assumed, therefore, that the inhibitory effect of anti-inflammatory drugs on the increase of tissue permeability is to some degree caused by the inhibition of anti-inflammatory drugs on M activities.