Hypervitaminosis A in the Rat Eighteen Figures

Abstract

As an extension of previous investigations (Rodahl, '49b), the effect of an excess of vitamin A on rats has been studied in further detail. Oral administration of an excess of vitamin A produced the same toxic symptoms as subcutaneous injection. Prolonged administration of an excess of vitamin A in toxic doses over a period of several days was necessary to produce the changes characteristic of the condition called hypervitaminosis A. No significant effect of age or sex was observed on the clinical picture of hypervitaminosis A in rats given equivalent daily doses of the vitamin, per gram of body weight. Gross doses of over 50 to 100 I.U. vitamin A/gram of body weight daily resulted in appreciable toxic manifestations. While doses of between 47 and 135 I.U. vitamin A/gram of body weight produced only slight toxic symptoms, doses of between 200 and 500 I.U. caused pronounced clinical symptoms, and doses over 800 I.U./gram of body weight proved lethal in all cases at the end of periods varying from 9 to 30 days. The symptoms following ingestion of toxic doses of vitamin A were: changes in the pelts, drowsiness, muscular weakness, lack of appetite, reduced growth, soreness and bleeding of the skin, alopecia, swelling of the palpebrae, exophthalmos, stiffness in the limbs, limping, spontaneous fractures, hemorrhages, proteinuria, hematuria, intestinal bleeding, and in some cases hypochromic or normochromic anemia. The fasting blood sugar was reduced in one case and increased in two cases. No abnormalities were detected in the content of calcium, phosphorus, total base, potassium and urea in the blood, and no significant difference was detected in the differential blood count when compared with that of normal rats. X-ray and microscopic examination of the long bones revealed characteristic changes, while no significant changes were detected in the mineral content of the bones. Histologically, the most constant findings were hyperemia, scattered red blood cells outside the capillaries in the internal organs and in the space of Bowman's capsule in the kidney, degeneration of the renal tubules, deposits of sudanophil droplets in the liver and increased sudanophil deposits in the adrenal cortex. Several of the clinical symptoms in hypervitaminosis A were found to correspond to histological changes attributed to the toxic effect of an excess of vitamin A. The mechanism of this toxic effect on the cells is, however, unknown.