muramidase and Chemical-and-Drug-Induced-Liver-Injury

Highly refined mineral hydrocarbons (MHCs) such as low melting point paraffin wax (LMPW) and low viscosity white oils can cause inflammatory changes in the liver and mesenteric lymph nodes (MLNs) of the Fischer-344 (F-344) rat. In contrast, only minimal MLN changes are seen in the Sprague-Dawley (S-D) rat with no changes in the liver. In this study, the response of female F-344 and S-D rats was compared after 90days dietary treatment with 0%, 0.2% or 2% LMPW. Effects in the F-344 rats were significantly greater than in the S-D rats: increased liver and splenic weights and inflammatory changes (hepatic microgranulomas) in these tissues were observed only in the F-344 rats. Microgranulomas in the MLNs were observed in both strains but the effects were substantially greater in the F-344 rats. Cellular markers of inflammation were examined in a subset of rats from each group using immunohistochemical staining. An increase in staining for CD3 (T-cells), CD8a (suppresser/cytotoxic T-cells) and CD4 (helper T-cells) correlated with an increase in lymphoid cells in the livers of treated F-344 rats. The majority of macrophages in the hepatic microgranulomas of treated F-344 rats were negative for the ED2 marker, indicating a likely origin from non-resident macrophages. Electron microscopy showed Kupffer cell hypertrophy and hyperplasia in treated F-344 rats. However, lysozyme staining (indicating activation of epithelioid macrophages) decreased with increasing granuloma size. Non-ED2 expressing cells may have been recruited but not sufficiently activated to be lysozyme positive. Inflammatory changes in the cardiac mitral valve noted in previous studies of LMPW were also seen in the F-344 rats in this study but not in the S-D rats. Chemical analysis showed that MHC accumulated in livers from treated F-344 but not S-D rats and the concentration was more than 2-fold greater in MLNs from the F-344 than from the S-D rats. The F-344 appears to be more immunologically sensitive to a number of agents than other rat strains and the results of this study suggest that this may contribute, along with pharmacokinetic differences, to the inflammatory response of F-344 rats to dietary MHCs.

Topics: Animals; Blood Cell Count; Blood Chemical Analysis; CD3 Complex; CD4-CD8 Ratio; Chemical and Drug Induced Liver Injury; Diet; Female; Hemoglobins; Immunohistochemistry; Liver; Lymph Nodes; Microscopy, Electron; Muramidase; Organ Size; Paraffin; Rats; Rats, Inbred F344; Rats, Sprague-Dawley; Species Specificity; Tissue Distribution; Viscosity

Acute toxic hepatitis in male Wistar rats was produced by single injection of 40% CCl(4) (0.2 ml per 100 g body weight in oil). Pretreatment with various immunostimulators (bacterial polysaccharides prodigiozan and salmozan; yeast polysaccharides zymosan, peptidoglycan, and mannan; and hydrolytic enzyme egg lysozyme) produced a hepatoprotective effect correlating which the stimulatory influence on macrophages and increasing in the following order: mannan

Topics: Adjuvants, Immunologic; Alanine Transaminase; Animals; Carbon Tetrachloride; Chemical and Drug Induced Liver Injury; Liver; Macrophages; Mannans; Muramidase; Peptidoglycan; Polysaccharides, Bacterial; Prodigiozan; Prostaglandins E; Rats; Rats, Wistar; Zymosan

The radioimmunoassay (RIA) as a high sensitive detection method for rat lysozyme (LZM) was established and applied to determine LZM excretion in urine from rats treated with tubulotoxic chemicals in order to establish a sensitive method of detecting minor renal damage. Rat LZM which showed a single protein band on sodium dodecylsulfate polyacrylamide gel electrophoresis was purified by ion-exchange chromatography and gel filtration. The assay sensitivity of the established RIA using the purified rat LZM was 4-256 ng/ml rat LZM and was about 20 times the turbidity method. The concentration of LZM in normal rat urine was 76.2 +/- 6.0 ng/ml (mean +/- SE, n = 50) using the RIA. In urine containing more than 100 ng/ml LZM, a high correlation between the values determined by the RIA and those by the turbidity method was observed. However, egg white LZM, human urinary LZM and guinea pig urinary LZM were not detectable by the RIA. Using the RIA, it was ascertained that urinary LZM excretion began to increase on day 5 in rats treated with gentamicin (15 or 30 mg/kg/day sc for 17 days), during the 6-9 h period in the rats treated with mercuric chloride (1 mg/kg sc), and during the 0-3 h period in the rats treated with p-aminophenol (1 mmol/kg sc). These significant increases in LZM excretion were not detectable by the turbidity method; therefore, it was concluded that this RIA for rat LZM was very useful for detection of minor renal damage.

Topics: Aminophenols; Animals; Chemical and Drug Induced Liver Injury; Gentamicins; Male; Mercuric Chloride; Muramidase; Nephelometry and Turbidimetry; Radioimmunoassay; Rats; Rats, Inbred Strains

Antitoxic effect of lysozyme was shown on a model of experimental acute toxic hepatitis of rats and mice. Administration of lysozyme to the animals in a dose of 5 mg/kg 24 hours before administration of carbon tetrachloride markedly decreased the level of morphological damages in the liver tissue and promoted a decrease in increased levels of alanine aminotransferase in blood serum. Higher levels of lysozyme in blood serum and cells of mouse peritoneal exudate 3 hours after administration of lysozyme were observed. The role of lysozyme as one of the main products secreted by activated macrophages in providing the general and antitoxic resistance of hepatocytes is discussed. Possible use of lysozyme as a hepatoprotective agent is suggested.

Topics: Animals; Carbon Tetrachloride Poisoning; Chemical and Drug Induced Liver Injury; Liver; Male; Mice; Mice, Inbred C57BL; Mice, Inbred CBA; Muramidase; Rats; Rats, Inbred Strains

The dynamics of natural resistance factors (complement, lysozyme, the bactericidal potency of blood serum) were found to be similar in rabbits with the toxic lesions of the liver resulting from the administration of carbon tetrachloride and in intact homologous rescipients receiving the serum of poisoned animals. Simultaneously a decrease in the complement titre and an increase in lysozyme activity and in the bactericidal potency of blood serum were observed. The effect thus revealed could be suppressed by treating the serum with contrical, a polyvalent proteinase inhibitor.

Topics: Animals; Blood Bactericidal Activity; Carbon Tetrachloride Poisoning; Chemical and Drug Induced Liver Injury; Complement System Proteins; Immunity; Immunity, Innate; Lysine; Muramidase; Rabbits; Time Factors

Topics: Animals; Chemical and Drug Induced Liver Injury; Liver; Mice; Muramidase; Rats

Topics: Amides; Animals; Antibodies; Bilirubin; Carbon Tetrachloride Poisoning; Chemical and Drug Induced Liver Injury; Cryptococcosis; Ethanol; Hexachlorocyclohexane; Hyperbilirubinemia; Iron; Liver; Liver Diseases; Male; Muramidase; Naphthalenes; Necrosis; Nitrosamines; Protein Deficiency; Rats; Sulfhydryl Compounds; Thiocyanates