thioacetamide and Hemorrhage

Liver diseases and regeneration are associated with hemodynamic changes denoting pathological alterations. Determining and monitoring physiological and pathological liver changes is essential for diagnostic and therapeutic objectives. Our aim was to determine the feasibility of functional magnetic resonance imaging (fMRI) during hypercapnia and hyperoxia for monitoring liver pathology. Liver fMRI images were acquired in rodents following acute bleeding, partial hepatectomy, and fibrosis. Results were quantitated and confirmed by histology. Changes induced by hyperoxia and hypercapnia following hemorrhage significantly correlated with the percentage of blood loss, reflecting lower liver perfusion and diminished vessel responsiveness to gas saturation. Hepatectomy resulted in an early decline in signal intensity changes due to hyperoxia, suggesting a decrease in liver perfusion and blood content. Following hepatectomy, signal intensity changes due to hypercapnia increased, signifying a change in liver perfusion from a mainly portal to a more arterial source. Two weeks after induction of fibrosis, signal intensity changes due to hypercapnia became much lower and those due to hyperoxia were much higher than those in normal livers, reflecting the increased perfusion due to the inflammatory process as confirmed by histologic analysis. With fibrosis progression, signal intensity changes induced by hypercapnia and hyperoxia were gradually attenuated, indicating structural and functional alterations of the liver vasculature during fibrosis.. In various liver pathologies, fMRI response to hypercapnia and hyperoxia is sensitive to changes in liver hemodynamic status involved in hepatic damage or recovery; thus, this technique may offer an additional noninvasive diagnostic tool for evaluation and follow-up of liver diseases by means of examining perfusion-related alterations.

Topics: Animals; ATP Binding Cassette Transporter, Subfamily B; ATP-Binding Cassette Sub-Family B Member 4; Disease Models, Animal; Hemorrhage; Hepatectomy; Hypercapnia; Hyperoxia; Liver; Liver Cirrhosis; Magnetic Resonance Imaging; Male; Mice; Mice, Knockout; Models, Biological; Rats; Rats, Sprague-Dawley; Thioacetamide

5-Fluoromethylornithine (5FMOrn) is a selective inactivator of ornithine aminotransferase. Its administration causes a dramatic increase of ornithine concentrations in all tissues. Treatment of mice with 20 mg.kg-1 5FMOrn shortly before or after a lethal dose (600 mg.kg-1, intraperitoneally) of thioacetamide (TAA), followed by a second dose 24 hr later, prevented death of 60% of the mice. Pathologic symptoms of TAA intoxication (liver haemorrhage, elevation of amino acids in blood and tissues, diminution of liver spermidine and spermine concentrations, elevation of the activity of liver enzymes in the plasma) were significantly ameliorated by the treatment. The liver protective action of 5FMOrn is related to the elevation of ornithine concentration, as appears from the fact that other, less selective inactivators of ornithine aminotransferase, also produced some protection against acute intoxication with TAA, but not a structurally related compound with no effect on this enzyme.

Topics: Amino Acids; Ammonia; Animals; Biogenic Polyamines; Chemical and Drug Induced Liver Injury; Hemorrhage; Liver Diseases; Male; Mice; Ornithine; Ornithine-Oxo-Acid Transaminase; Pilot Projects; Poisoning; Thioacetamide

The radiation protective action of 2,2'-Dithiobis(N-[(1-adamantyl)-methyl]-acetamidine)-dihyrochloride (S-75) and cysteamine was compared in splenectomized and non-splenectomized mice. Cysteamine was found to have better and more general protection properties. Several indications of a specific effect of S-75 on the spleen were observed. It is suggested that the protection properties of S-75 should be tested in another laboratory animal not having such a marked splenic haemopoiesis as the mouse.

Topics: Acetamides; Adamantane; Animals; Body Weight; Cysteamine; Hematopoiesis; Hemorrhage; Male; Mice; Mice, Inbred CBA; Organ Size; Radiation-Protective Agents; Spleen; Splenectomy; Thioacetamide

CBA male mice were irradiated with single doses of 7.1, 8.6, 10.0, 11.4 or 12.8 Gy, respectively. A protective substance, 2,2-Dithiobis(N-[(1-adamantyl)methyl]acetamidine)-dihydrochloride, here called S-75, was administered orally, 45 min before start of irradiation. Cysteamine-HCl was used as a reference protective substance. Pathologic and haematologic examination of irradiated animals was performed. Cysteamine had somewhat better protective abilities than did S-75, but the latter had some other properties which indicate its possible usefulness in practice.

Topics: Acetamides; Adamantane; Administration, Oral; Animals; Body Weight; Bridged-Ring Compounds; Cysteamine; Drug Evaluation, Preclinical; Hemorrhage; Lethal Dose 50; Male; Mice; Mice, Inbred CBA; Organ Size; Radiation Injuries, Experimental; Radiation-Protective Agents; Thioacetamide