chlortetracycline and Chemical-and-Drug-Induced-Liver-Injury

Topics: Aminosalicylic Acids; Anemia, Hemolytic; Bile Ducts; Bilirubin; Chemical and Drug Induced Liver Injury; Chloramphenicol; Chlortetracycline; Cholelithiasis; Cholestasis; Erythromycin; Halothane; Heart Valve Prosthesis; Hepatitis A; Humans; Hypoxia; Isoniazid; Jaundice; Liver; Liver Diseases; Methoxyflurane; Necrosis; Pancreatitis; Postoperative Complications; Sulfonamides; Transfusion Reaction

Topics: Ampicillin; Antitubercular Agents; Asparaginase; Chemical and Drug Induced Liver Injury; Chloramphenicol; Chlortetracycline; Erythromycin; Griseofulvin; Humans; Liver Diseases; Methicillin; Oleandomycin; Oxytetracycline; Penicillins; Rifampin; Tetracycline

Topics: Absorption; Acne Vulgaris; Bacteria; Bacteriuria; Bronchial Diseases; Chemical and Drug Induced Liver Injury; Chemical Phenomena; Chemistry; Chlortetracycline; Demeclocycline; Drug Eruptions; Humans; Infections; Kidney Diseases; Methacycline; Oxytetracycline; Protein Binding; Tetracycline; Tooth Discoloration

Drug-induced liver injury is one of the main causes of drug attrition. The ability to predict the liver effects of drug candidates from their chemical structures is critical to help guide experimental drug discovery projects toward safer medicines. In this study, we have compiled a data set of 951 compounds reported to produce a wide range of effects in the liver in different species, comprising humans, rodents, and nonrodents. The liver effects for this data set were obtained as assertional metadata, generated from MEDLINE abstracts using a unique combination of lexical and linguistic methods and ontological rules. We have analyzed this data set using conventional cheminformatics approaches and addressed several questions pertaining to cross-species concordance of liver effects, chemical determinants of liver effects in humans, and the prediction of whether a given compound is likely to cause a liver effect in humans. We found that the concordance of liver effects was relatively low (ca. 39-44%) between different species, raising the possibility that species specificity could depend on specific features of chemical structure. Compounds were clustered by their chemical similarity, and similar compounds were examined for the expected similarity of their species-dependent liver effect profiles. In most cases, similar profiles were observed for members of the same cluster, but some compounds appeared as outliers. The outliers were the subject of focused assertion regeneration from MEDLINE as well as other data sources. In some cases, additional biological assertions were identified, which were in line with expectations based on compounds' chemical similarities. The assertions were further converted to binary annotations of underlying chemicals (i.e., liver effect vs no liver effect), and binary quantitative structure-activity relationship (QSAR) models were generated to predict whether a compound would be expected to produce liver effects in humans. Despite the apparent heterogeneity of data, models have shown good predictive power assessed by external 5-fold cross-validation procedures. The external predictive power of binary QSAR models was further confirmed by their application to compounds that were retrieved or studied after the model was developed. To the best of our knowledge, this is the first study for chemical toxicity prediction that applied QSAR modeling and other cheminformatics techniques to observational data generated by the means of automate

Topics: Animals; Chemical and Drug Induced Liver Injury; Cluster Analysis; Databases, Factual; Humans; MEDLINE; Mice; Models, Chemical; Molecular Conformation; Quantitative Structure-Activity Relationship

It was shown on 99 male albino rats that vitamin E, sodium selenite and Astragalus. L. infusion used separately lowered the toxic effect of tetracycline on the liver, while the use of vitamin E in combination with sodium selenite or Astragalus L. infusion prevented such an effect of the antibiotic. This was evident from the decreased levels of lipid peroxidation products, i.e. diene conjugates and malonic dialdehyde in the blood and liver, and a simultaneous increase in the ratio of sulfhydryl and disulfide groups in these biosubstrates. Parallelism of the changes in these indices of the blood and liver was observed. It is suggested that lipid peroxidation plays an important part in the pathogenesis of liver affection with tetracyclines. The combined use of vitamin E and selenium-containing drugs is considered advisable for the prophylaxis and treatment of such affections.

Topics: alpha-Tocopherol; Animals; Chemical and Drug Induced Liver Injury; Chlortetracycline; Drug Evaluation, Preclinical; Lipid Peroxides; Liver; Male; Oxidation-Reduction; Plant Extracts; Rats; Selenious Acid; Selenium; Tetracycline; Tocopherols; Vitamin E

Studies on albino rats showed that high doses of tetracycline-induced damages of the liver evident from increased activity of serum enzymes (alanine aminotransferase, aspartate aminotransferase and alkaline phosphatase) and inhibition of bile secretion, synthesis and secretion of bile acids and cholesterol excretion. Administration of vitamin E, sodium selenite, infusion of Astragalus L. and especially vitamin E combinations with sodium selenite markedly or completely arrested the occurrence of hepatotoxic properties of tetracycline. It is suggested that the use of vitamin E combinations with selenium-containing preparations is advisable in the prophylaxis and treatment of tetracycline-induced damages of the liver.

Topics: Animals; Bile; Chemical and Drug Induced Liver Injury; Chlortetracycline; Drug Evaluation, Preclinical; Liver; Liver Diseases; Male; Plant Extracts; Rats; Selenious Acid; Selenium; Tetracycline; Vitamin E

Topics: Anti-Bacterial Agents; Chemical and Drug Induced Liver Injury; Child; Chloramphenicol; Chlortetracycline; Fatty Liver; Female; Hepatitis; Oxytetracycline; Pregnancy; Pregnancy Complications; Prochlorperazine; Tetracycline; Toxicology

Topics: Anti-Bacterial Agents; Black People; Chemical and Drug Induced Liver Injury; Chlortetracycline; Demeclocycline; Female; Hepatitis; Hepatitis A; Humans; Kidney Diseases; Liver; Maternal-Fetal Exchange; Oxytetracycline; Pharmacology; Pregnancy; Pregnancy Complications; Tetracycline; Tetracyclines; Tooth; Toxicology; Urine

Topics: Anemia; Anemia, Aplastic; Anti-Bacterial Agents; Antibiotics, Antitubercular; Bacitracin; Chemical and Drug Induced Liver Injury; Chloramphenicol; Chlortetracycline; Erythromycin; Hearing Disorders; Hepatitis; Kidney Diseases; Neomycin; Oleandomycin; Streptomycin; Tetracycline; Toxicology

Topics: Animals; Cell Respiration; Chemical and Drug Induced Liver Injury; Chlortetracycline; Liver; Rats; Respiration

Topics: Anti-Bacterial Agents; Chemical and Drug Induced Liver Injury; Chloramphenicol; Chlortetracycline; Liver; Oxytetracycline; Streptomycin

Topics: Chemical and Drug Induced Liver Injury; Chlortetracycline

Topics: Animals; Chemical and Drug Induced Liver Injury; Chloramphenicol; Chlortetracycline; Dogs; Liver; Mice; Oxytetracycline

Topics: Chemical and Drug Induced Liver Injury; Chlortetracycline; Chronic Disease; Fatty Liver; Liver Diseases; Oxytetracycline

Topics: Chemical and Drug Induced Liver Injury; Chlortetracycline; Digestion; Fats