ABSTRACT
BACKGROUND: Number of drugs is used in human medicine for a long time therapy. Their side effects on lipid metabolism are mostly unknown. Clinical testing of drugs concerns usually biochemical parameters involved in the liver and kidney function. The aim of our study was to search the effect of ibuprofen on the lipid composition in the important organs. Ibuprofen was chosen as a representative of currently used nonsteroidal antiinflammatory drugs. METHODS AND RESULTS: Group of 14 Crl-NMRI-BR male mice, approximately 8 weeks old, 30.5 +/- 1.2 g initial body mass, was used in the experiment. Animals were divided into 2 identical groups. One of them received 0.6 mg of ibuprofen per day (animal model for human dose 1200 mg/day) in the diet for a period of 6 weeks. After this time, animals were killed by decapitation, individual organs were excised, washed with physiological saline and lyophilized. Total lipid content was determined gravimetrically. Individual lipid classes were separated by thin-layer chromatography. Fatty acid profiles (in the form of methyl esters) in these lipid classes were analyzed by capillary gas chromatography using fused silica column 25 m x 0.25 mm I.D. with the chemically bonded stationary phase CP-WAX 52 CB (Chrompack, The Netherlands). The treatment resulted in the increased body mass of 7.9 +/- 1.7 g, which, in comparison with that of control group (4.9 +/- 3.4 g) was not statistically significant. Liver mass increased from 1.62 +/- 0.21 g to 1.86 +/- 0.19 g (p < 0.05). Total lipid content in the liver increased from 52.8 +/- 15.4 to 91.7 +/- 10.9 mg/g (p < 0.01). Changes in the fatty acid composition were most important in the kidney tissue. Relative levels of polyunsaturated fatty acids increased in phosphatidylethanolamine from 27.6 +/- 6.1 mol% to 33.9 < 0.6 mol% (p < 0.05) for n6 fatty acids and from 8.7 +/- 2.1 to 14.7 +/- 1.1 mol% (p < 0.001) for n3 fatty acids. These changes were compensated by the opposite ones in the relative content of saturated fatty acids from 49.7 +/- 7.0 mol% to 41.1 +/- 0.7 mol% (p < 0.05) and monoenoic fatty acids from 14.0 +/- 2.0 mol% to 10.4 +/- 0.9 mol% (p < 0.01). Changes in the fatty acid composition of the liver and heart lipids were mostly not statistically significant. CONCLUSIONS: An unusual component was observed in the triacylglycerol fraction of heart tissue, which was identified by the gas chromatography-mass spectrometry as a mixture of approximately 80% of isopropyl myristate and 20% of isopropyl palmitate. Absolute content of this component was not determined.
Subject(s)
Ibuprofen/pharmacology , Lipid Metabolism , Animals , Chromatography, Gas , Gas Chromatography-Mass Spectrometry , Kidney/metabolism , Liver/metabolism , Male , Mice , Myocardium/metabolismABSTRACT
Crl:NMRI-BR male mice received 0.6 mg/day of ibuprofen (animal model for human dose 1200 mg/day) in the diet for a period of 6 weeks. This treatment resulted in increased body mass, liver mass, and total lipid content in the liver tissue. Changes in the fatty acid composition in the individual lipid classes were most important in kidney tissue; levels of polyunsaturated fatty acids were increased in phospholipids and decreased in neutral lipids. These changes were compensated for by opposite changes in the levels of saturated and monoenoic acids. Similar changes were also observed in liver and heart lipids. An increased level of an unusual component was observed in heart tissue, which was identified as isopropyl myristate by GC-MS and verified by comparing the mass spectra and retention times with those of synthetic standards.
