Prevention by hydrocortisone of changes in connective tissue induced by an excess of vitamine A acid in Amphibia.

Abstract

Experiments described elsewhere have suggested that cortisone can protect the cartilage of rabbits from dissolution by an excess of vitamin A.1 These findings are in keeping with the general hypothesis that vitamin A in excess releases protease(s) from lysosomes both in vitro and in vivo,2-5 and that the action of lysosomal protease is responsible for the subsequent degradation of chondromucoprotein in cartilage matrix.2'3 In contrast, cortisol and its analogues have been shown to retard the release of acid protease from lysosomes0'7 and to protect cartilage matrix against an excess of vitamin A.5 Thus it was unexpected, when hypervitaminosis A was induced in the larvae of Xenopus laevis by vitamin A alcohol,9 to find that the simultaneous administration of hydrocortisone accelerated rather than retarded the damage caused by the vitamin.10 One possible explanation for this phenomenon was that the steroid caused the release of vitamin A from liver stores into the circulation; such an action has been recently documented by McGillivray. Were this effect sufficient to explain the acceleration by hydrocortisone of hypervitaminosis A in Xenopus, one would expect protection by the steroid against an excess of vitamin A acid. The acid form of the vitamin, in contrast to vitamin A alcohol which is stored as the ester, is not stored in liver to any degree.'2 The experiments to be described below have shown that hydrocortisone did, in fact, protect connective tissue of Xenopus laevis against vitamin A acid in excess. The vitamin caused kyphoscoliosis, collapse of rostral tentacles, and frank hemorrhage in the tadpoles; all of these findings were significantly less frequent in larvae given hydrocortisone concurrently. To extend these observations, the effects of thyroxine and epsilon-amino caproic acid (EACA) on hypervitaminosis A in toad larvae were also studied. The former agent initiates metamorphosis, while the latter agent would inhibit the activators of plasmin which could be responsible for some of the lesions in hypervitaminotic larvae.