The influence of protein-calorie malnutrition (PCM) on the anti-inflammatory activity (suppression of carrageenan-induced paw edema and pleurisy) of salicylate was studied in Sprague-Dawley male rats. For this purpose, animals were fed a 21% (control) or a 5% (PCM) protein diet ad libitum or a control diet in restricted amounts (pair-fed). A significant increase in the anti-inflammatory activity of salicylate was observed in PCM but not in pair-fed rats. PCM caused a decrease in plasma salicylate (assayed by HPLC) concentration (due to increased synthesis of glycine conjugate and elimination), no change in tissue distribution, and a moderate decrease in serum protein binding of salicylate. PCM exerted inconsistent effects on the activities of liver lysosomal enzymes (activities of (beta)-glucuronidase decreased, of acid phosphatase did not change, and of aryl salfatase increased) and there was no relationship between the lysosome stabilizing and anti-inflammatory activities of salicylate and other aspirin-like drugs (indomethacin and oxyphenbutazone). It was therefore concluded that the PCM-induced increase in the anti-inflammatory activity of salicylate was primarily not due to any changes in its pharmacokinetics or in its effects on lysosomal membranes. The biosynthesis of prostaglandins and leukotrienes was studied because of their important role in inflammatory processes. PCM decreased the biosynthesis by pleural neutrophils of both cyclooxygenase-independent (major products: thromboxane B(,2) and 12-hydroxy-5,8,10-heptadecatrienoic acid) and lipoxygenase-dependent (leukotriene B(,4)) metabolites of arachidonic acid. The biosynthesis of prostaglandins E(,2) and F(,2(alpha)) by renal medulla homogenates and of prostaglandin D(,2) and 12-hydroxy-5,8,10,14-eicosatetraenoic acid by spleen homogenates were also reduced by PCM. At all concentrations of aspirin studied, the amounts of these metabolites were less in preparations from PCM than from control animals. Ho
| Identifer | oai:union.ndltd.org:LACETR/oai:collectionscanada.gc.ca:QMM.71861 |
| Date | January 1984 |
| Creators | Yue, Tian Li. |
| Publisher | McGill University |
| Source Sets | Library and Archives Canada ETDs Repository / Centre d'archives des thèses électroniques de Bibliothèque et Archives Canada |
| Language | English |
| Detected Language | English |
| Type | Electronic Thesis or Dissertation |
| Format | application/pdf |
| Coverage | Doctor of Philosophy (Department of Pharmacology and Therapeutics.) |
| Rights | All items in eScholarship@McGill are protected by copyright with all rights reserved unless otherwise indicated. |
| Relation | alephsysno: 000219104, proquestno: AAINK66580, Theses scanned by UMI/ProQuest. |
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