Gene/Protein Disease Symptom Drug Enzyme Compound
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Query: UMLS:C0038002 (splenomegaly)
 9,873 document(s) hit in 31,850,051 MEDLINE articles (0.00 seconds)

Drug-metabolizing enzyme activities, cytochrome concentration, and protein content of hepatic microsomal preparations from adult, female Sprague-Dawley rats were examined at 1-, 3-, 6-, 10-, 14- and 17-day intervals after administration of a single intravenous injection of Corynebacterium parvum (C. parvum) at a dose of 10 mg/m2. Aniline hydroxylase (AH) activity, aminopyrine demethylase (APD) activity, and cytochrome P-450 concentration were reduced 20-50% on days 3-6 and, thereafter, gradually recovered to control levels by day 17. Cytochrome c reductase activity and cytochrome b5 concentration were reduced significantly (24%) only on day 10. Microsomal protein concentration was unchanged. C. parvum added in vitro had no effect on AH or APD activity. Although livers of treated rats were only slightly (less than 20%) enlarged, gross splenomegaly was apparent, reaching a maximum on day 6. A marked inverse correlation existed between the temporal variation in the size of the spleen and APD activity. In rats killed 6 days after administration of C. parvum at 0.67 to 10.00 mg/m2, a direct relationship was apparent between the adjuvant dose and the magnitude of reduction of APD activity. A similar relationship was apparent between splenomegaly and APD activity. Histopathologic examination of liver sections from treated rats revealed numerous granulomas throughout the parenchyma. The magnitude of enzyme inhibition generally paralleled the severity of the hepatic lesions.
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PMID:Inhibition of hepatic drug metabolism in the rat after Corynebacterium parvum treatment. 684 17

In rats, surgical creation of a portacaval shunt leads to hepatic atrophy and lowered levels of cytochrome P450, the key component of liver enzymes involved with drug metabolism. These effects are largely attributable to diversion of portal blood away from the liver and not to decreased hepatic blood flow. The present study has established a simpler model of portal blood diversion in order to examine the role of portal blood constituents in the regulation of hepatic cytochrome P450. Portal vein ligation was performed on male Wistar rats in which portasystemic anastomoses had been produced by subcutaneous transposition of the spleen. Portal vein ligation resulted in portal hypertension, as evidenced by splenomegaly, and in hepatic atrophy. In liver of rats with portal vein ligation, microsomal cytochrome P450 levels were significantly less than in sham-operated control rats, but cytochrome b5, NADPH-cytochrome c reductase, and glucose-6-phosphatase were unaltered. The activities of four mixed function oxidases also were reduced significantly in the liver of rats with portal vein ligation, the changes being greatest for ethylmorphine N-demethylase, a prototype substrate for the phenobarbital-inducible isoenzyme of cytochrome P450. In contrast, the activity of microsomal heme oxygenase, the rate-limiting step in catabolism of heme to bilirubin, was enhanced after portal vein ligation. Experiments in pair-fed rats showed that the changes observed in liver from rats with portal vein ligation could not be attributed to caloric deprivation. Administration of phenobarbital increased liver mass, cytochrome P450 levels, and mixed function oxidase activities both in rats with portal vein ligation and in controls, indicating that the liver of the ligated rats retained considerable protein synthetic capacity. It appears that hepatic atrophy and lowering of cytochrome P450 levels that follow portal vein ligation are consequences of altered exposure of the liver to factors normally present in portal blood, and that the same alterations may also enhance heme oxygenase activity.
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PMID:Portal vein ligation selectively lowers hepatic cytochrome P450 levels in rats. 686 53