methylcellulose and Liver-Diseases

Our objectives were to identify serum marker proteins in rats that might serve as sensitive indicators of hepatomegaly, hepatocellular necrosis, or hepatobiliary injury and to use them to analyze data from a collaborative proteomics project.. In each of 4 studies comprising the collaborative project, rats were given 1 of 4 compounds that target the liver through different mechanisms. Sera and liver samples were collected by terminal bleeds at 1 of 3 postdose time points. Sera were depleted of major secretory proteins and then separated into protein features by 2-dimensional gel electrophoresis (2DGE). Liver specimens were also processed and subjected to 2DGE. Protein spots that significantly increased or decreased in quantity after drug treatment were recovered, digested, analyzed by mass spectroscopy, and compared with available databases for identification. Criteria for further consideration were (a) temporal expression (i.e., increase or decrease at early, fulminant, or recovery periods), (b) known biological function, (c) probable hepatic origin, and (d) any previous association with toxicity in published studies. Markers that changed significantly at the early time point were important because of their potential sensitivity for signaling minimal damage.. Vitamin D-binding protein, paraoxonase, cellular retinol-binding protein, malate dehydrogenase, F-protein, and purine nucleoside phosphorylase were identified as empirically confirmed serum markers for hepatic effects in drug-treated rats.. Proteomics can be applied for the identification and confirmation of peripheral biomarkers for altered liver function after toxicant exposure.

Topics: 1-Naphthylisothiocyanate; Acetaminophen; Animals; Biomarkers; Chemical and Drug Induced Liver Injury; Disease Models, Animal; Dose-Response Relationship, Drug; Hypertrophy; Liver Diseases; Male; Methylcellulose; Organ Size; Phenobarbital; Proteomics; Pyrimidines; Rats; Rats, Sprague-Dawley; Sensitivity and Specificity

Carboxymethylcellulose (CMC) (1% in 0.9% NaCl, 0.2 ml/10 g ip) a common suspending agent, enhanced adriamycin (ADR) (15 mg/kg ip) toxicity when administered to mice 5 hr before the antibiotic. Compared with ADR alone, this combination treatment produced, after 7 days, an increase in lethality from 15 to 80%. The pathologic analysis of hearts, livers, kidneys, and small bowels was performed, revealing an increase in the incidence and severity of hepatic damage in mice receiving ADR + CMC. Furthermore, reduced glutathione (GSH) was measured in livers of all mice; the animals treated with CMC and ADR + CMC showed a significant (p less than 0.01) reduction of hepatic GSH in comparison with controls and ADR-alone-treated animals. These data further confirm a crucial protective role for GSH in ADR toxicity and prove that CMC exerts an important biochemical effect on hepatic GSH.

Topics: Animals; Carboxymethylcellulose Sodium; Chemical and Drug Induced Liver Injury; Doxorubicin; Drug Interactions; Glutathione; Liver Diseases; Methylcellulose; Mice

A marked increase of serum transaminase activities, histological changes of livers similar to those seen in viral hepatitis in man, and inhibition of hepatic protein synthesis were observed in rats following a single injection of D-galactosamine-HCl. These galactosamine-induced phenomena were prevented by the pretreatment of polyriboinosinic acid-polyribocytidylic acid 24 h before the galactosamine administration.

Topics: Alanine Transaminase; Animals; Aspartate Aminotransferases; Carboxymethylcellulose Sodium; Chemical and Drug Induced Liver Injury; Galactosamine; Liver; Liver Diseases; Male; Methylcellulose; Necrosis; Peptides; Poly I-C; Polylysine; Rats; Rats, Inbred Strains

Topics: Alkaline Phosphatase; Animals; Aspartate Aminotransferases; Bilirubin; Biopsy; Cholesterol; Diet; Dogs; Enteral Nutrition; Female; Gelatin; Humans; Ileum; Jejunum; L-Lactate Dehydrogenase; Liver; Liver Diseases; Methylcellulose; Obesity; Protein Deficiency; Triglycerides

Topics: Kidney Diseases; Leukopenia; Liver Diseases; Lung Diseases; Lymph Nodes; Lymphocytosis; Metabolic Diseases; Methylcellulose; Pathology; Rats; Research; Spleen; Toxicology