Gene/Protein Disease Symptom Drug Enzyme Compound
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Query: UMLS:C0008370 (cholestasis)
 9,378 document(s) hit in 31,850,051 MEDLINE articles (0.00 seconds)

In the field of gene expression analysis, DNA microarray technology is having a major impact on many different areas including toxicology. For instance, a number of studies have shown that transcription profiling can generate the information needed to assign a compound to a mode-of-action class. In this study, we investigated whether compounds inducing similar toxicological endpoints produce similar changes in gene expression. In vitro primary rat hepatocytes were exposed to 11 different hepatotoxicants: acetaminophen, amiodarone, clofibrate, erythromycin estolate, isoniazid, alpha-naphtylylisothiocyanate, beta-naphtoflavone, 4-pentenoic acid, phenobarbital, tetracycline, and zileuton. These molecules were selected on the basis of their variety of hepatocellular effects observed such as necrosis, cholestasis, steatosis, and induction of CYP P450 enzymes. We used a low-density DNA microarray containing 59 genes chosen as relevant toxic and metabolic markers. The in vitro gene expression data generated in this study were generally in good agreement with the literature, which mainly concerns in vivo data. Furthermore, gene expression profiles observed in this study have been confirmed for several genes by real-time PCR assays. All the tested drugs generated a specific gene expression profile. Our results show that even with a relatively limited gene set, gene expression profiling allows a certain degree of classification of compounds with similar hepatocellular toxicities such as cholestasis, necrosis. The clustering analysis revealed that the compounds known to cause steatosis were linked, suggesting that they functionally regulate similar genes and possibly act through the same mechanisms of action. On the other hand, the drugs inducing necrosis and cholestasis were pooled in the same cluster. The drugs arbitrarily classified as the CYP450 inducers formed individual clusters. In conclusion, this study suggests that low-density microarrays could be useful in toxicological studies.
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PMID:Use of a low-density microarray for studying gene expression patterns induced by hepatotoxicants on primary cultures of rat hepatocytes. 1288 83

Administration of Aacetylsalicylic acid in children with viral infections (influence B, chickenpox) can be related with development of Reye syndrome - severe encephalopathy and liver insufficiency with mortality in 50% of cases. During Reye syndrome most important is deficiency of carnitine and hepatocyte damage. Decreased amount of carnitine impairs the energy function of mitochondria and gluconeogenesis as well as production of urea. As a result develops toxic encephalopathy and liver insufficiency. The goal of the research was assessment of efficacy of L-Carnitine, Corvitin and their combination on functional state of liver in experimental model of Reye Syndrome in rats. The study was performed on mature white male Wistar rates with body mass 150-180g. 50 rats were randomly divided into 5 groups (10 rats in each group). The model of Reye syndrome was induced in accordance with A.Vengersky's method. Intraperitoneal administration of 4-pentenoic acid was performed once daily during seven days, the used dosage was 20mg/kg. The treatment of toxic hepatitis was carried with intraperitoneal administration of L-Carnitine 300mg/kg, Corvitine 100mg/kg and concurrent administration of these drugs. Monotherapy with Corvitin and L-Carnitin successfully improved liver function and equally decreased indicators of hepatocyte's cytolyses and increased levels of glucose and urea. The markers of cholestasis was slightly more improved during use of L-Carnitine. Simultaneous use of both drugs was effective in rats with Reye syndrome, indicators of liver damage normalized and herewith, no mortality outcome was observed. The most pronounced hepatoprotective effect of concurrent administration of L-Carnitine and Corvitin may be due to synergic action of these drugs and such regime can be recommended for correction of liver function during Reye syndrome.
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PMID:[ACTION OF L-CARNITINE, CORVITIN AND THEIR COMBINATION ON FUNCTIONAL STATE OF LIVER IN EXPERIMENTAL MODEL OF REYE SYNDROME IN RATS]. 2845 36