Effects of tetracycline on ultrastructure and lipoprotein secretion in the rat hepatocyte

Abstract

Fat droplets, 0.1–0.5 μm, accumulated in the space of Disse of hepatocytes in rats treated ip with 300 mg/kg of tetracycline hydrochloride. This change occurred in both pregnant and unbred females and in males but was not observed in similar rats treated with 100 mg/kg which showed typical steatosis induced by tetracycline. Ultrastructural changes in mitochondria, rough and smooth endoplasmic reticulum (SER) were similar to those previously reported. Uptake of iv administered palmitic [9-10- 3H]acid in rats treated with 300 mg/kg was not appreciably impaired. One hour after an injection of 300 mg/kg, the antibiotic concentration was 10 times greater in the liver than in the serum. From 1 to 6 hr the concentrations increased from roughly 300 to 800 μg/g of liver. In rats treated with 100 mg/kg, no concentrations above 200 μg/g were observed during a 48-hr postinjection period. Under in vitro conditions, tetracycline complexed with lipoprotein in a precipitate when a concentration greater than 200 μg/ml was obtained in rat blood serum. In the hepatocyte of rats treated with 300 mg/kg it was presumed that as the antibiotic concentration rose above 200 μg/g nascent very low density lipoprotein complexed rapidly with it. The complexed lipoprotein was channeled in dilated SER in the manner of liposomes to the sinusoidal surface and discharged from vesicles into the space of Disse. The plasma membrane of the hepatocyte showed loss of microvilli and surface distortion. The space of Disse became distended with insoluble fat droplets from 6 hr to 3 days after injection.