Gene/Protein Disease Symptom Drug Enzyme Compound
Pivot Concepts:   Target Concepts:
Query: UNIPROT:P17174 (aspartate aminotransferase)
 14,872 document(s) hit in 31,850,051 MEDLINE articles (0.00 seconds)

We determined whether the paracrine liver endothelin (ET) system participates in the pathogenesis of CCl4-induced hepatotoxicity. Wistar-Kyoto rats were divided into four groups: a bosentan-treated group with CCl4 intoxication, a vehicle-treated group with CCl4 intoxication, a nontreated control group, and a bosentan-treated control group. Hepatotoxicity was assessed by determination of serum levels of alanine aminotransferase (ALT), aspartate aminotransferase (AST) and lactate dehydrogenase (LDH). Tissue ET-1 concentrations and expression of endothelin receptor subtypes were analyzed. The liver tissue levels of ET-1 in rats with CCl4 intoxication were significantly higher than in normal rats. Scatchard analysis revealed no differences in the density and binding constants of ETA and ETB receptors between rats with CCl4 intoxication and controls. Bosentan treatment of rats undergoing CCl4 inhalation resulted in significant protection against elevation of ALT, AST, LDH, and bilirubin. In conclusion, this study showed that the paracrine ET system in involved in the pathogenesis of CCl4-induced hepatotoxicity and that blockade of the stimulated liver endothelin system reduces CCl4-induced liver injury.
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PMID:Protective effects of the mixed endothelin receptor antagonist bosentan in rats with CCL4-induced liver injury. 858 41

This study analyzed if the paracrine liver endothelin system participates in the pathogenesis of CCl4-induced hepatotoxicity. Wistar Kyoto rats were divided into four groups: a bosentan (mixed endothelin ETA and ETB receptor antagonist) treated group with CCl4 intoxication, a vehicle treated group with CCl4 intoxication, a nontreated control group and a bosentan treated control group. Hepatotoxicity was assessed by determination of alanine aminotransferase (ALT), aspartate aminotransferase (AST), lactate dehydrogenase (LDH) followed by histopathological examinations. Tissue endothelin-1 concentrations and expression of endothelin receptor subtypes were analyzed. The tissue levels of endothelin-1 in the liver of rats with CCl4 intoxication were significantly higher than those in normal rats. Scatchard analysis revealed no differences in the density and binding constant of endothelin ETA and ETB receptor between rats with CCl4 intoxication and controls. Bosentan treatment of rats undergoing CCl4 inhalation resulted in a significant protection against elevation of ALT, AST, LDH and bilirubin. Histopathological examination of live sections for necrotic, swollen and lipid-laden cells revealed findings that were in agreement with the serum enzyme data. In conclusion, this study showed that the paracrine endothelin system is involved in the pathogenesis of CCl4-induced hepatotoxicity and that the blockade of the stimulated liver endothelin systems reduces CCl4-induced liver injury.
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PMID:Role of the paracrine liver endothelin system in the pathogenesis of CCl4-induced liver injury. 874 89

The present study was designed to investigate if TAK-044, a novel endothelin (ET) ETA/ETB receptor antagonist, inhibits ischemia-reperfusion liver injury. The initial study showed the presence of both ETA and ETB receptors in canine hepatic membrane fractions using the specific binding assay of labeled ET-1 with ET isomers and TAK-044. The nonselective ETA/ETB receptor antagonist TAK-044 inhibited the specific binding of ET-1 to the receptors in a concentration-dependent manner. In subsequent studies using a canine 70% partial liver ischemic model (60 minutes), we found that an intravenous injection of TAK-044 (3 mg/kg) before ischemia significantly inhibited the release of serum liver enzymes (aspartate transaminase, alanine transaminase, mitochondrial glutamic oxaloacetic transaminase, and an increase of indocyanine green retention rate after reperfusion, compared with the control group. Elevation of the portal venous pressure was also suppressed significantly during the portal triad occlusion, and a rapid restoration of oxygen pressure in the liver tissue after reperfusion was observed in the TAK-044-treated group. Morphometric analysis revealed that the hepatocyte swelling and sinusoidal contraction 1 hour after reperfusion were significantly less severe in the treated group than in the control group. The sludging of erythrocytes in the sinusoidal lumens was also minimal in the treated group. In conclusion, the significant suppression of hepatic microcirculatory disturbance and tissue injury after ischemia-reperfusion were shown in the TAK-044-treated group. This finding indicates that the pretreatment of TAK-044 is useful as a hepatoprotective agent against ischemia-reperfusion injury, which is otherwise produced by a pathway involving ET-1.
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PMID:Hepatoprotective effect of the endothelin receptor antagonist TAK-044 against ischemia-reperfusion injury in the canine liver. 909 1