Effect of aminopterin administration on the metabolism of liver and small intestine of guinea pigs and rats.

Small amounts of Aminopterin, one of the antifolic metabolites, produce gastrointestinal effects such as nausea, vomiting, melena, and diarrhea in human beings (1, 2) and destruction of the epithelial elements in experimental animals (3, 4). A single injection of 240 y of Aminopterin per kilo of body weight had no morphological effect when administered to young adult rats, but caused a marked reduction in oxygen uptake by gastrointestinal mucosa within 24 hours, followed by degeneration of all epithelial elements and subsequent massive hemorrhage into the gastrointestinal tract. Structural changes were always preceded by a decrease in oxygen uptake by intestinal mucosa (4). The guinea pig and the rabbit (5, 6) are more resistant to Aminopterin toxicity than is the rat. To investigate further the effect of Aminopterin on different animal species, the following comparative studies of the effect of Aminopterin on guinea pigs and rats were undertaken.