orabase and Chemical-and-Drug-Induced-Liver-Injury

Dioscorea bulbifera L. is a medicinal plant. The present study was undertaken to investigate the hepatotoxicity induced by D. bulbifera in mice. Through the acute toxicity of various extracts including the EtOAc fraction (EF) and the non-EtOAc fraction (Non-EF) from ethanol, and the ethanol itself, we found that the EF contains the toxic ingredients of D. bulbifera rhizome. On this basis, to study the hepatotoxicity induced by the toxic ingredients, mice were treated with 0.5% sodium carboxymethyl cellulose (CMC-Na) alone or the EF of D. bulbifera rhizome at doses of 80, 160, 320, and 480 mg/kg once daily i.g. for fourteen consecutive administrations. Serum samples were collected for determination of the biomarkers for liver injury, such as, alanine transaminase (ALT) and aspartate transanimase (AST). Hepatic tissues were used to assay for the level of lipid peroxide (LPO), amounts of antioxidants such as glutathione, and activities of antioxidant-related enzymes for liver oxidative-antioxidative status in mice. The results showed that ALT and AST were significantly elevated after fourteen consecutive administrations of the EF of D. bulbifera rhizome. In addition, the level of LPO increased remarkably, while the glutathione amounts, and the activities of the antioxidant-related and glutathione-related enzymes including superoxide dismutase (SOD), glutathione peroxidase (GPx), glutathione-S-transferase (GST), glutathione reductase (GR) and glutamate-cysteine ligase (GCL) of hepatic tissues all decreased conspicuously, in livers of mice treated with the EF of D. bulbifera rhizome. Taken together, our results indicate that the EF contains the main toxic ingredients of D. bulbifera rhizome, and the mechanism of hepatotoxicity induced by it may be due to liver oxidative stress injury in mice.

Topics: Alanine Transaminase; Analysis of Variance; Animals; Aspartate Aminotransferases; Carboxymethylcellulose Sodium; Chemical and Drug Induced Liver Injury; Dioscorea; Dose-Response Relationship, Drug; Glutathione; Glutathione Peroxidase; Glutathione Transferase; Lipid Peroxidation; Mice; Plant Extracts; Rhizome; Superoxide Dismutase

Topics: Animals; Carboxymethylcellulose Sodium; Chemical and Drug Induced Liver Injury; Cyclooctanes; Dioxoles; Lignans; Liver; Male; Plant Extracts; Plants, Medicinal; Polycyclic Compounds; Polysorbates; Rats; Rats, Inbred Strains; Solvents; Transaminases

This study was undertaken to determine if interactions of toxicological significance might occur during treatment of mice with paracetamol (P) and carboxymethylcellulose (CMC). P (300 mg/kg) administration induced only slight hepatic morphologic changes and lowered hepatic reduced glutathione (GSH) to 40% of the level in controls, when measured 1 hour after treatment. Intraperitoneal pretreatment with CMC (1% in NaC1, 20 ml/kg), significantly decreased GSH concentration (to 19% of controls) and severely enhanced hepatic injury. Such an interaction is of considerable significance since both CMC and P are widely used substances in experimental pharmacology and clinical practice.

Topics: Acetaminophen; Animals; Carboxymethylcellulose Sodium; Chemical and Drug Induced Liver Injury; Glutathione; Liver; Male; Methylcellulose; Mice; Time Factors

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