VENO-OCCLUSIVE LESIONS IN LIVERS OF RATS FED CROTALARIA FULVA.

WHEN cirrhosis of the liver in Jamaican infants was first described by McFarlane and Branday in 1945 a suggestion was made that the disease might be due to the toxic action of herbs, used by the native population (so called bush-teas). The underlying liver lesion (i.e. occlusion of the centrilobular hepatic vein and subsequent centrilobular fibrosis) was not recognised until 1954 (Bras, Jelliffe and Stuart) and the illness was then named veno-occlusive disease of the liver (VOD). Fibrosis of this type may lead to cirrhosis of the liver and it is estimated that in Jamaica VOD is responsible for 30 per cent of cirrhosis found at autopsy (Bras, Brooks and Watler, 1961). Animals known to have died following the ingestion of ragwort (Senecio species), also have occlusive lesions apparently comparable to human VOD (Bras, Berry and Gyorgy, 1957; Bras et al., 1954). Senecio, however, is only rarely being used as a bush-tea in Jamaica. A study of VOD patients in Barbados definitely incriminated another plant, (C,rotalaria retusa (Stuart and Bras, 1956). When this lead was followed in Jamaica it was learned that Crotalaria fulva was a well recognised bush-tea. Crotalaria and Senecio both contain pyrrolizidine alkaloids known to be liver toxins (Schoental, Regina and Magee, 1959). For several years efforts have been made in our laboratory to reproduce VOD in animals by the oral administration of Crotalaria fulva infusions, i.e. approximating the conditions believed to lead to the disease in the Jamaicani population. These experiments were successful in cows (Bras et al., 1957) and in goats (Lindo and Bras, unpublished), but in rats positive results have been obtained rarely and inconstantly (Hill, Stephenson and Filshie, 1958, reported occlusive lesions in rats but following intra-peritoneal injections). A different experimental design, described in this paper, has now enabled us to produce VOD in rats with regularity. Identical results were obtained in both laboratories, Jamaica and Philadelphia. The histological events leading up to the appearance of the occlusive lesioni are described. Abnormalities of serum and liver transaminase levels and of liver glycogen and water content are also described and their relevance to a proposed pathogenesis of the lesion is discussed.