Mercury, copper and bismuth compounds react in vivo with insoluble collagen in a way similar to gold thiosulphate. The introduction of artificial cross-links increases the overall stability of the collagen and lowers its solubility. As a result the fibrils acquire a more finely detailed cross-striation pattern as seen under the electron microscope.In the preceding papers [l --41 it was shown that gold as the thiosulphate complex reacts with collagen in vivo and has a stabilising effect on the collagen structure similar to that shown in vitro by other heavy metals which yield aqno-and amo-complex compounds. The use of heavy metals in human medicine is not exceptional ; thus bismuth and copper are used in the treatment of inflammatory rheumatic diseases as well as gold, and mercury finds use as a diuretic. This work was designed to establish whether these metals show a reaction with collagen in vivo similar to that of gold.
MATERIALS AND METHODSI n these investigations male rats (Wistar or Sprague-Dawley) of initial body weight 100 & 5 g were used. Five groups, 7-8 animals in each, were treated as follows : a ) controls ; b) with bismuth (bismuth hydroxide and bismuth nitrate 2: 1 ; Alubi, Spofa Prague) in weekly doses 1 .O mg bismuth per 100 g body weight ;c) with copper, as the copper(I1) complex of diethyl-amino-8-hydroxyquinoline sulphate, the main constituent of Decuprene (Union Chimique, Belgium) in weekly doses of 0.3 mg per 100 g body weight ;d) with gold: gold sodium thiosulphate, (Sanocrysin, Ferrosan, Denmark), in weekly doses of 2.0 mg per I00 g body weight;e) with mercury: as N-(2-carboxypropyl)-N'-(2-hydroxymercuri-3-methoxy) urea, the main constituent of Mercuretin (Spofa, Prague) in weekly doses of 1.0 mg per body weight.All compounds were injected intramuscularly once a week for 4 weeks or, where rat tail tendons were to be used in electron microscopic investigations, for 11 weeks.The tail tendons were investigated as described in detail elsewhere In the rat skins total nitrogen, hydroxyproline, neutral-salt-soluble collagen, acid-soluble collagen and insoluble collagen were determined. The solubility of the acid-insoluble collagen in 2 M potassium thiocyanate and 6 M urea and on incubation with pronase was determined as described in detail elsewhere [4]. The values were determined in duplicate.
Nitrogen was determined according to Strauch [S]and hydroxyproline according to Stegemann [9]. The electron microscopic investigations were carried out with a Siemens Elmiskop I at 80 kV.
RESULTSLike gold thiosulphate the mercury, copper and bismuth compounds have a stabilising effect on collagen after four weeks treatment. The tail tendons exhibit a higher shrinkage temperature (see Table), a lower swelling and a longer contraction-relaxation time (Fig.l) than those of the control animals. The longer contraction-relaxation time after mercury treatment is particularly marked.The analyses of the skins as presented in the Table show no conspicuous changes a€ter treatment with the heavy metal, nor has the neu...
