shu-508 and Chemical-and-Drug-Induced-Liver-Injury

To determine whether contrast ultrasonography can affect the sinusoidal cells and platelets of the liver by using ultrastructural analysis in vivo.. Fifteen Wistar rats were placed into the following 5 groups of 3 rats each: 3 control groups comprising a sham operation group, a contrast agent injection-alone group, and an ultrasound exposure-alone group; and 2 contrast agent injection with ultrasound exposure groups, split according to excision time. After a dose of an echo contrast agent (100 mg/kg of body weight) was administered through the femoral vein, the rats that received injections were subjected to ultrasound for the first minute, no ultrasound for the next 4 minutes, and then ultrasound sweep scanning for 10 seconds. The rats were perfused via the heart with cold physiologic saline containing 2% paraformaldehyde and 2.5% glutaraldehyde solution buffered with 0.1-mol/L phosphate. The livers of the rats in 4 of the groups were excised immediately. The livers of the rats in 1 of the 2 contrast agent with ultrasound exposure groups were excised by the same procedure 5 hours after they received the injections. All specimens were studied with light and electron microscopy.. Platelet aggregation and injury to endothelial cells were more severe in the contrast agent injection and ultrasound exposure groups than in the other groups.. Contrast ultrasonography can cause platelet aggregation and endothelial cell damage in the rat hepatic sinusoid.

Topics: Animals; Chemical and Drug Induced Liver Injury; Contrast Media; Endothelium; Liver; Liver Diseases; Male; Microscopy, Electron; Platelet Aggregation; Polysaccharides; Rats; Rats, Wistar

The aim of the study was to investigate the etiology of cecal and hepatic lesions in mice and rats after intravenous administration of gas-carrier contrast agents (GCAs). A modified fluorescein flowmetry technique and 24 h necropsy were used in mice (conventional and germ free), rats, and guinea pigs after GCA administration. Different diets and oral nonabsorbable antibiotics were used. Nonfluorescence, edema, congestion, hemorrhage, and mucosal erosion in cecum and colon and nonfluorescent areas in the liver were observed from 16 min after GCA administration in conventional mice on standard diet. Numerous gas bubbles (>50 microm) were observed in the vasculature around the nonfluorescent areas of cecum and colon and in mesenteric vessels draining to the portal vein. Acute inflammation, edema, hemorrhage, and ulceration of the cecum and colon and liver necrosis were seen 24 h after GCA administration in conventional mice on standard diet. When mice were maintained on either a diet with glucose as the only carbohydrate source or on a standard diet supplemented with antibiotics, uniform fluorescence and no organ lesions were observed after GCA administration. Uniform fluorescence and no organ lesions were observed in germ-free mice, rats, and guinea pigs dosed with GCAs and in control animals (mice, rats, and guinea pigs) dosed with sucrose. The results indicate that intravascular growth of GCA microbubbles occurs in the cecal and colonic wall of mice, leading to occlusive ischemia and necrosis in these intestinal segments and secondary gas embolisation in the liver. Transmural gas supersaturation in the cecal wall may explain the intravascular bubble growth in mice.

Topics: Albumins; Animal Feed; Animals; Cecal Diseases; Cecum; Chemical and Drug Induced Liver Injury; Contrast Media; Female; Ferric Compounds; Fluorocarbons; Gases; Guinea Pigs; Injections, Intravenous; Iron; Liver; Liver Diseases; Male; Mice; Mice, Inbred Strains; Microscopy, Fluorescence; Models, Animal; Oxides; Polysaccharides; Rats; Rats, Inbred Strains; Specific Pathogen-Free Organisms; Tissue Distribution; Ultrasonography