233 research outputs found
The principle of safety evaluation in medicinal drug - how can toxicology contribute to drug discovery and development as a multidisciplinary science? -
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Toxicokinetics in the process of drug development-its significance and practical problems-
No full textMolecular Toxicological Approach for Drug Safety Assessment-Toxicity-outbreak Related to Toxicogenomics, Toxicoproteomics and Metabolomics-
No full textLipid metabolism in nonspecific productive inflammatory tissue Part 1. Changes in lipid composition and fatty acid component of each lipid class
No full textGranulomatous inflammation was induced in rats by subcutaneous implantation of formalin-soaked filter paper and lipid classes in inflammatory tissue were investigated. An increase in triglyceride content was observed in parallel with the formation of adipose tissue in the early stage of inflammation. In the stage of growth of granulomatous tissue, phospholipids increased with the gradual decrease in triglyceride content. In the early stage of granulomatous tissue formation, triglycerides contained mainly saturated fatty acid (16:0) and unsaturated fatty acids (18:1 (ω-9), 18:2 (ω-6) and 18:3 (ω-3)). Phospholipids in the growing stage of granulomas contained mainly polyunsaturated fatty acids (20:4 (ω-6) and 22:4 (ω-6)). Rapid and selective in vitro and in vivo incorporation of radio-labelled unsaturated fatty acids (20:3 (ω-6), 20:4 (ω-6), 20:5 (ω-3)) into phospholipids was observed in granulomatous tissue. These results suggested that fatty acids released by lipolytic degradation of triglycerides in adipose tissue in the early stage of granulomatous inflammation are converted into phospholipids in cells accumulating in maturing granulation tissues, and also that these dynamic changes in lipid metabolism play important roles in the progress of inflammatory processes
Toxic effect onset and evaluations of medicinal drugs - horizon for Darwinian toxicological thought -
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Lipid metabolism in nonspecific productive inflammatory tissue Part 2. Incorporation of polyunsaturated fatty acids into phospholipids and effects of anti-inflammatory drugs on lipid dynamics
No full textFatty acid dynamics in phospholipids and incorporation of radio-labelled fatty acids into phospholipid fractions were examined, using granulation tissue induced by the implantation of formalin-soaked filter paper in rats. The effects of anti-inflammatory drugs on lipid dynamics were also studied. Concomitant with the progress of granulomatous inflammation, an increase in polyunsaturated fatty acids (mainly 20:4 (ω-6)) content of phospholipids was observed. Differing from saturated fatty acids, labelled polyunsaturated fatty acids (20:3 (ω-6), 20:4 (ω-6) and 20:5 (ω-3)) were easily incorporated in vivo into phosphatidylinositol and phosphatidylethanolamine in addition to phosphatidylcholine of granulation tissue. Indomethacin, tenoxicam and dexamethasone administered p. o. inhibited the granuloma formation. Indomethacin and tenoxicam had no marked effect on the tissue lipid composition. However, in dexamethasonetreated rats, tissue lipids were almost exclusively composed of triglycerides. Indomethacin and tenoxicam slightly decreased the percentages of 18:2 (ω-6) and 20:4 (ω-6) in phospholipid fractions.
Thus, polyunsaturated fatty acids released by lipolysis from fat cells accumulated in local inflammatory tissue in the early stage may be transferred into membrane phospholipids of inflammatory cells of later stage of inflammation and influence their functions. Antiinflammatory drugs may cause functional changes in cells accumulated in granulation tissue by changing the fatty acid components of the phospholipids
Aromatic retinoid Ro 40-8757 reduces immunotoxicities of cyclophosphamide as revealed by immunohistochemical staining of lymphoid tissues and general pathologic examinations.
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