RESUMEN
In people who do not have clinical immunity to malaria, infection with the malaria parasite could lead to severe complications. We describe a patient who had acute and severe lung injury from malaria. A 37-year-old woman had a 24-hour history of generalized weakness and chills 2 days after returning from Nigeria. She had received mefloquine as prophylaxis, but the patient did not take the medication. On admission, a thick blood smear revealed severe Plasmodium falciparum parasitemia. She was given doxycycline and quinine, but as her parasitemia resolved, dyspnea and hypoxemia developed and she consequently required placement of an endotracheal tube. Chest radiography results showed bilateral and diffuse infiltrate. This report shows that patients with P falciparum malaria should be monitored closely and transferred to an intensive care unit for additional management if respiratory distress develops. Physicians caring for patients who have recently traveled to malaria-endemic areas need to anticipate the possible development of malaria with all of its complications, including acute lung injury.
Asunto(s)
Malaria Falciparum/complicaciones , Síndrome de Dificultad Respiratoria/etiología , Adulto , Animales , Femenino , Humanos , Malaria Falciparum/tratamiento farmacológico , Nigeria , Plasmodium falciparum/aislamiento & purificación , Radiografía , Síndrome de Dificultad Respiratoria/diagnóstico por imagen , ViajeRESUMEN
The aim of the present study was to elucidate the effects of a single dose of 3-thia fatty acids (tetradecylthioacetic acid and 3-thiadicarboxylic acid) over a 24-hr study period on the expression of genes related to peroxisomal and mitochondrial beta-oxidation in liver of rats. The plasma triglyceride level decreased at 2-4 hr, 4-8 hr, and 8-24 hr, respectively, after a single dose of 150, 300, or 500 mg of 3-thia fatty acids/kg body weight. Four to eight hours after administration of 3-thia fatty acids, a several-fold-induced gene expression of peroxisomal multifunctional protein, fatty acyl-CoA oxidase (EC 1.3.3.6), fatty acid binding protein, and 2,4-dienoyl-CoA reductase (EC 1.3.1.43) resulted, concomitant with increased activity of 2,4-dienoyl-CoA reductase and fatty acyl-CoA oxidase. The expression of carnitine palmitoyltransferase-I and carnitine palmitoyltransferase-II increased at 2 and 4 hr, respectively, although at a smaller scale. In cultured hepatocytes, 3-thia fatty acids stimulated fatty acid oxidation after 4 hr, and this was both L-carnitine- and L-aminocarnitine-sensitive. The hepatic content of eicosapentaenoic acid and docosahexaenoic acid decreased throughout the study period. In contrast, the hepatic content of oleic acid tended to increase after 24 hr and was significantly increased after repeated administration of 3-thia fatty acids. Similarly, the expression of delta9-desaturase was unchanged during the 24-hr study, but increased after feeding for 5 days. To conclude, carnitine palmitoyltransferase-I expression seemed to be induced earlier than 2,4-dienoyl-CoA reductase and fatty acid binding protein, and not later than the peroxisomal fatty acyl-CoA oxidase. The expression of delta9-desaturase showed a more delayed response.
Asunto(s)
Carnitina O-Palmitoiltransferasa/biosíntesis , Ácidos Dicarboxílicos/farmacología , Ácido Graso Desaturasas/biosíntesis , Hígado/efectos de los fármacos , Microcuerpos/enzimología , Mitocondrias/enzimología , Proteínas de Neoplasias , Proteínas del Tejido Nervioso , Oxidorreductasas actuantes sobre Donantes de Grupo CH-CH , Oxidorreductasas/biosíntesis , ARN Mensajero/análisis , Sulfuros/farmacología , Acil-CoA Oxidasa , Animales , Carnitina O-Palmitoiltransferasa/genética , Proteínas Portadoras/biosíntesis , Proteínas Portadoras/genética , Fraccionamiento Celular , Colesterol/sangre , Ácido Graso Desaturasas/genética , Proteína de Unión a los Ácidos Grasos 7 , Proteínas de Unión a Ácidos Grasos , Hígado/enzimología , Masculino , Proteína P2 de Mielina/biosíntesis , Proteína P2 de Mielina/genética , Oxidorreductasas/genética , Ácido Palmítico/farmacología , Fosfolípidos/sangre , Ratas , Ratas Wistar , Factores de Tiempo , Triglicéridos/sangreAsunto(s)
Ácidos Docosahexaenoicos/farmacología , Ácido Eicosapentaenoico/farmacología , Hígado/efectos de los fármacos , Triglicéridos/metabolismo , Animales , Colesterol/metabolismo , Aceite de Maíz/metabolismo , Aceite de Maíz/farmacología , Ácidos Docosahexaenoicos/metabolismo , Ácido Eicosapentaenoico/metabolismo , Hígado/citología , Hígado/metabolismo , Microcuerpos/efectos de los fármacos , Microcuerpos/metabolismo , Microsomas Hepáticos/efectos de los fármacos , Microsomas Hepáticos/metabolismo , Mitocondrias/efectos de los fármacos , Mitocondrias/metabolismo , RatasRESUMEN
Administration of tetradecylthioacetic acid (a 3-thia fatty acid) increases mitochondrial and peroxisomal beta-oxidative capacity and carnitine palmitoyltransferase activity, but reduces free fatty acid and triacylglycerol levels in plasma compared to palmitic acid-treated rats and controls. The decrease in plasma triacylglycerol was accompanied by a reduction (56%) in VLDL-triacylglycerol. Prolonged supplementation of tetradecylthioacetic acid caused a significant increase in lipogenic enzyme activities (ATP-citrate lyase and acetyl-CoA carboxylase) and diacylglycerol acyltansferase, but did not affect phosphatidate phosphohydrolase. Plasma cholesterol, LDL- and HDL-cholesterol levels were reduced. 3-Hydroxy-3-methylglutaryl-coenzyme A reductase activity was, however, stimulated in 3-thia fatty acid-treated rats compared to controls. In addition. the mRNAs of 3-hydroxy-3-methylglutaryl-coenzyme A reductase and LDL-receptor were increased. Tetradecylthioacetic acid administration affected the fatty acid composition in plasma and liver by increasing the amount of monoenes, especially 18:1(n-9), mostly at the expense of omega-3 fatty acids. Compared to liver a large amount of tetradecylthioacetic acid accumulated in the heart, and this accumulation was accompanied by an increase in omega-3 fatty acids, particularly 22:6(n-3) and a decrease in omega-6 fatty acids, mainly 20:4(n-6). The results show that the hypolipidemic effect of tetradecylthioacetic acid is sustained after prolonged administration and may, at least in part, be due to increased fatty acid oxidation and upregulated LDL-receptor gene expression. The increase in lipogenic enzyme activities as well as increased 3-hydroxy-3-methylglutaryl-coenzyme A reductase activity, may be compensatory mechanisms to maintain cellular integrity. Decreased level of 20:4(n-6) combined with increased omega-3/omega-6 ratio in cardiac tissue after tetradecylthioacetic acid treatment may have influence on membrane dynamics and function.
Asunto(s)
Ácidos Grasos/metabolismo , Lípidos/sangre , Sulfuros/farmacología , Animales , Peso Corporal/efectos de los fármacos , Colesterol/biosíntesis , Epidídimo/efectos de los fármacos , Epidídimo/metabolismo , Ácidos Grasos/sangre , Ácidos Grasos/química , Corazón/efectos de los fármacos , Riñón/efectos de los fármacos , Riñón/metabolismo , Hígado/efectos de los fármacos , Hígado/enzimología , Hígado/metabolismo , Masculino , Lípidos de la Membrana/metabolismo , Mitocondrias/efectos de los fármacos , Mitocondrias/metabolismo , Tamaño de los Órganos/efectos de los fármacos , Oxidación-Reducción , Ratas , Ratas Wistar , Sulfuros/administración & dosificación , Triglicéridos/biosíntesis , Triglicéridos/sangreRESUMEN
Fish oils rich in n-3 fatty acids have been shown to decrease plasma lipid levels, but the underlying mechanism has not yet been elucidated. This investigation was performed in order to further clarify the effects of purified ethyl esters of eicosapentaenoic acid (EPA-EE) and docosahexaenoic acid (DHA-EE) on lipid metabolism in rats. The animals were fed EPA-EE, DHA-EE, palmitic acid, or corn oil (1 g/kg/d) by orogastric intubation along with a chow background diet for three months. At the end the animals were sacrificed. Plasma and liver lipids were measured, as well as lipid-related enzyme activities and mRNA levels. The fatty acid composition of plasma and different tissues was also determined. This study shows that, compared to the corn oil control, EPA-EE and DHA-EE lowered plasma cholesterol level, whereas only EPA-EE lowered the amount of plasma triacylglycerol. In liver peroxisomes, both EE preparations increased fatty acyl-CoA oxidase FAO activities, and neither altered 3-hydroxy-3-methylglutaryl (HMG)-CoA reductase activities. In liver microsomes, EPA-EE raised HMG-CoA reductase and acyl-CoAicholesterol acyltransferase activities, whereas DHA-EE lowered the former and did not affect the latter. Neither product altered mRNA levels for HMG-CoA reductase, low density lipoprotein-receptor, or low density lipoprotein-receptor related protein. EPA-EE lowered plasma triacylglycerol, reflecting lowered very low density lipoprotein secretion, thus the cholesterol lowering effect in EPA-EE-treated rats may be secondary to the hypotriacylglycerolemic effect. An inhibition of HMG-CoA reductase activity in DHA-EE treated rats may contribute to the hypocholesterolemic effect. The present study reports that 20:5n-3, and not 22:6n-3, is the fatty acid primarily responsible for the triacylglycerol lowering effect of fish oil. Finally, 20:5n-3 was not converted to 22:6n-3, whereas retroconversion of 22:6n-3 to 20:5n-3 was observed.
Asunto(s)
Colesterol/sangre , Grasas Insaturadas en la Dieta/farmacología , Ácidos Docosahexaenoicos/farmacología , Ácido Eicosapentaenoico/farmacología , Ácidos Grasos/sangre , Tejido Adiposo/metabolismo , Animales , Aceite de Maíz/farmacología , Grasas Insaturadas en la Dieta/administración & dosificación , Ácidos Docosahexaenoicos/administración & dosificación , Ácido Eicosapentaenoico/administración & dosificación , Ácidos Grasos/metabolismo , Hidroximetilglutaril-CoA Reductasas/metabolismo , Hígado/metabolismo , Hígado/ultraestructura , Masculino , Ácido Palmítico/farmacología , Ratas , Ratas WistarRESUMEN
The mechanism behind the hypolipidemic effect of tetradecylthioacetic acid (CMTTD, a non-beta-oxidizable 3-thia fatty acid) was studied in hamsters fed a high cholesterol diet (2%), which resulted in hyperlipidemia. Treating hyperlipidemic hamsters with CMTTD resulted in a progressive hypocholesterolemic and hypotriacylglycerolemic effect. Decreased plasma cholesterol was followed by a 39% and 30% reduction in VLDL-cholesterol and LDL-cholesterol, respectively. In contrast, the HDL-cholesterol content was not affected, thus decreasing the VLDL-cholesterol/HDL-cholesterol and LDL-cholesterol/HDL-cholesterol ratios. 3-Hydroxy-3-methylglutaryl- (HMG) CoA reductase activity and its mRNA level were unchanged after CMTTD administration. Also, the LDL receptor and LDL receptor-related protein (LRP-4) mRNAs were unchanged. The decrease in plasma triacylglycerol was accompanied by a 45% and 56% reduction in VLDL-triacylglycerol and LDL-triacylglycerol, respectively. The hypolipidemic effect of CMTTD was followed by a 1.4-fold increase in mitochondrial fatty acid oxidation and a 2.3-fold increase in peroxisomal fatty acid oxidation. CMTTD treatment led to an accumulation of dihomo-gamma-linolenic acid (20:3n-6) in liver, plasma, very low density lipoprotein, and heart. Noteworthy, CMTTD accumulated more in the heart, plasma, and VLDL particles compared to the liver, and in the VLDL particle alpha-linolenic acid (18:3n-3) decreased whereas eicosatetraenoic acid (20:4n-3) increased. In addition, linoleic acid (18:2n-6) and the total amount of polyunsaturated fatty acids decreased, the latter mainly due to a decrease in n-6 fatty acids. The present data show that CMTTD was detected in plasma and incorporated into VLDL, liver, and heart. The relative incorporation (mol%) of CMTTD was heart > VLDL > liver. In conclusion, CMTTD causes both a hypocholesterolemic and hypotriacylglycerolemic effect in hyperlipidemic hamsters.
Asunto(s)
Colesterol en la Dieta/sangre , HDL-Colesterol/sangre , LDL-Colesterol/sangre , Ácidos Grasos/metabolismo , Hipolipemiantes/metabolismo , Sulfuros/metabolismo , Animales , Cricetinae , Hipolipemiantes/farmacología , Masculino , Mesocricetus , Sulfuros/farmacologíaRESUMEN
The effects of prolonged administration (3 months) of a 3-thia fatty acid analogue and omega-3-fatty acids on cardiac fatty acid oxidation and the volume fraction of lipid droplets and mitochondria in cardiomyocytes were investigated. Doses were 1 g/day/kg body weight, except 150 mg/day/kg body weight for tetradecylthioacetic acid (a 3-thia fatty acid). One group served as control and did not receive any treatment. The volume fraction of lipid droplets in cardiomyocytes was significantly lower in the tetradecylthioacetic acid group compared to the other groups. Mitochondrial beta-oxidation was 60% greater and fatty acyl-CoA oxidase activity was increased by 430% in the tetradecylthioacetic acid group compared to control. This was accompanied by a greater volume fraction of mitochondria in cardiomyocytes (0.514 +/- 0.032% in tetradecylthioacetic acid v 0.318 +/- 0.007% in control) which was due to an increased size of mitochondria. The volume fraction of mitochondria was also greater in eicosapentaenoic acid (EPA) treated rats compared to control, but the enzymic activities were unaffected. Docosahexaenoic acid (DHA) treatment resulted in a greater volume fraction of lipid droplets in the cardiomyocytes, but the volume fraction of mitochondria and enzyme activities were unaltered. These results indicate that EPA and DHA have different effects on the modulation of mitochondrial biogenesis. Tetradecylthioacetic acid treatment results in megamitochondria formation and increased peroxisomal and mitochondrial beta-oxidation with a concomitant reduction of lipid droplets in the cardiomyocytes.
Asunto(s)
Ácidos Grasos/metabolismo , Lípidos/análisis , Mitocondrias Cardíacas/efectos de los fármacos , Miocardio/metabolismo , Sulfuros/farmacología , Animales , Masculino , Microscopía Electrónica , Mitocondrias Cardíacas/metabolismo , Dilatación Mitocondrial , Miocardio/ultraestructura , Oxidación-Reducción , Ratas , Ratas WistarRESUMEN
A simple and rapid method for the separation and identification of tissue levels of short chain coenzyme A (CoA) esters by a reversed-phase high-performance liquid chromatography with ultraviolet-visible adsorbance detection is described. Samples of liver, heart and kidney tissues were homogenised in 5% sulfosalicylic acid containing 50 microM of dithioerythritol in 1:9 w/v proportion. Following centrifugation, 20 microliters of the supernatant were directly injected onto a 3-micron ODS C18 column (100 x 4.6 mm I.D.). The separation of acetyl-CoA, malonyl-CoA, methylmalonyl-CoA, succinyl-CoA, propionyl-CoA and free CoASH was achieved in less than 20 min using gradient elution with sodium phosphate, sodium acetate and methanol at a constant flow-rate of 1.5 ml/min. The lowest detection limit was 3 pmol.
Asunto(s)
Cromatografía Líquida de Alta Presión/métodos , Coenzima A/metabolismo , Animales , Coenzima A/química , Frío , Ésteres , Riñón/metabolismo , Hígado/metabolismo , Masculino , Miocardio/metabolismo , Ratas , Ratas Wistar , Reproducibilidad de los Resultados , Espectrofotometría UltravioletaRESUMEN
The effects of sulfur-substituted fatty acid analogues on the subcellular distribution and activities of acetyl-CoA and propionyl-CoA hydrolases in rats fed a high carbohydrate diet were studied. Among subcellular fractions of liver homogenates from rats fed a high carbohydrate diet (20%), the acetyl-CoA and propionyl-CoA hydrolase activities are found in the mitochondrial, peroxisome-enriched and cytosolic fractions. We have shown that the subcellular distribution of acetyl-CoA hydrolase appears to be different from the distribution propionyl-CoA hydrolase activity. Thus, the highest specific activity of acetyl-CoA hydrolase was found in the mitochondrial fraction, whereas the highest specific activity of propionyl-CoA hydrolase was found in the peroxisome-enriched fraction. Rats treated with sulfur-substituted fatty acids, i.e., 3-thiadicarboxylic acid (400 mg/day per kg body weight), showed a significant increase in acetyl-CoA hydrolase activity where the peroxisomal and cytosolic hydrolases were increased 3.9- and 2.7-fold, respectively, compared to palmitic acid treated rats. Similar results were obtained with tetradecylthioacetic acid treated rats. Propionyl-CoA hydrolase activities, in rats treated with these two peroxisome proliferating fatty acid analogues showed increased activity mainly in the mitochondrial and the cytosolic subcellular fractions. Acetyl-CoA hydrolase activity was sensitive to NADH, whereas no stimulation of the propionyl-CoA hydrolase activity was observed in the presence of NADH. The hepatic amounts of acetyl-CoA, propionyl-CoA, and free CoASH were elevated after sulfur-substituted fatty acid treatment. Sulfur-substituted fatty acids also elevated the specific acetyl-CoA hydrolase activity in the mitochondrial fraction and the propionyl-CoA hydrolase activity in the light-mitochondrial fraction. These results, therefore, suggest that acetyl-CoA hydrolase and propionyl-CoA hydrolase are two distinct proteins and that these two enzymes have a multiorganelle localisation.
Asunto(s)
Acetil-CoA Hidrolasa/metabolismo , Ácidos Dicarboxílicos/farmacología , Carbohidratos de la Dieta/metabolismo , Hígado/enzimología , Sulfuros/farmacología , Tioléster Hidrolasas/metabolismo , Acetilcoenzima A/metabolismo , Acilcoenzima A/metabolismo , Animales , Coenzima A/metabolismo , Inducción Enzimática/efectos de los fármacos , Lípidos/biosíntesis , Hígado/ultraestructura , Masculino , NAD/metabolismo , Ratas , Ratas Wistar , Fracciones Subcelulares/enzimologíaRESUMEN
A single oral dose of two 3-thia (3-thiadicarboxylic and tetradecylthioacetic acids) and of 4-thia (tetradecylthiopropionic acid) fatty acids were administered to normolipidemic rats and their effects on lipid metabolism over a 24 hr period were studied. All three thia fatty acids could be detected in plasma 2 hr after treatment. Tetradecylthioacetic and tetradecylthiopropionic acids were detected in different hepatic lipid fractions but were incorporated mainly into hepatic phospholipids. Two hours after administration hepatic mitochondrial beta-oxidation and the total liver level of long-chain fatty acyl-CoA increased with a concomitant decrease in saturated fatty acids, total hepatic malonyl-CoA and plasma triacylglycerol levels in the 3-thia fatty acid groups. Tetradecylthiopropionic acid administration caused a decrease in mitochondrial beta-oxidation and an increase in plasma triacylglycerol at 24 hr. The activities of key lipogenic enzymes were unaffected in all treatment groups. Plasma cholesterol level was reduced only at 8 hr in 3-thiadicarboxylic acid treated rats although 3-hydroxy-3-methylglutaryl-CoA (HMG-CoA) reductase was suppressed already at 2, 4, 8 and 12 hr. The results show that thia fatty acids are rapidly absorbed and are systemically available after oral administration but the 3-thia fatty acids reached systemic circulation more slowly and less completely than the 4-thia fatty acid. Very low levels of the thia fatty acids are detected in plasma 24 hr after a single administration. They are incorporated into all hepatic lipid classes, especially phospholipids. Rapid incorporation of a non beta-oxidizable thia fatty acid into hepatic lipids may cause a diversion of other fatty acids from glycerolipid biosynthesis to mitochondrial beta-oxidation. Stimulation of mitochondrial beta-oxidation and suppression of HMG-CoA reductase are primary events, occurring within hours, after 3-thia fatty acid administration. The hypotriglyceridemic effect of the 3-thia fatty acids observed at 2-4 hr is independent of the activities of key lipogenic and triacylglycerol synthesising enzymes.
Asunto(s)
Ácidos Grasos/farmacología , Metabolismo de los Lípidos , Hígado/metabolismo , Ácidos Sulfurados/farmacología , Animales , Ácidos Dicarboxílicos/sangre , Inducción Enzimática , Lípidos/sangre , Hígado/efectos de los fármacos , Hígado/enzimología , Masculino , Propionatos/sangre , Ratas , Ratas Wistar , Sulfuros/sangre , Triglicéridos/sangreRESUMEN
To investigate the importance of factors influencing substrate availability for triacylglycerol biosynthesis on lipoprotein metabolism, the effects of two opposite-acting sulphur-substituted fatty acid analogues, tetradecylthioacetic acid and tetradecylthiopropionic acid were studied. Administration of tetradecylthioacetic acid to rats resulted in a reduction of plasma levels of triacylglycerols (44%) and cholesterol (26%). This was accompanied by a reduction in very-low-density lipoprotein (VLDL) triacylglycerols (48%), VLDL cholesterol (36%), low-density lipoprotein (LDL) cholesterol (36%) and high-density lipoprotein (HDL) triacylglycerols (50%), whereas HDL cholesterol levels did not change. Subsequently, the HDL/LDL-cholesterol ratio increased by 40%. The cholesterol-lowering effect was accompanied by a reduction in hydroxymethylglutaryl CoA (HMG-CoA) reductase activity (37%). Both mitochondrial and peroxisomal fatty acid oxidation increased (1.7-fold and 5.3-fold, respectively). Furthermore, there was a significant negative correlation between plasma triacylglycerols and mitochondrial fatty acid oxidation. Hepatic triacylglycerol synthesis was retarded, as indicated by a decrease in VLDL triacylglycerol secretion (40%), and by a reduced liver triacylglycerol content (29%). The activities of lipoprotein lipase and hepatic lipase in post-heparin plasma were not affected. Microsomal and cytosolic phosphatidate phosphohydrolase activities were inhibited (28% and 70%, respectively). Hepatic malonyl-CoA levels decreased by 29% and the total activity of acetyl-CoA carboxylase was reduced (23%). In hepatocytes treated with tetradecylthioacetic acid, mitochondrial fatty acid oxidation increased markedly (100%) and triacylglycerol secretion was reduced (40%). In tetradecylthiopropionic-acid-treated rats, a significant increase in both plasma and VLDL triacylglycerols was found (46% and 72%, respectively) but VLDL triacylglycerol secretion was unaffected. However, no effect on either plasma or lipoprotein cholesterol levels was seen. Mitochondrial fatty acid oxidation was decreased by 50% and hepatic triacylglycerol levels increased by 33%. In hepatocytes exposed to tetradecylthiopropionic acid, triacylglycerol synthesis increased (100%) while triacylglycerol secretion and fatty acid oxidation remained unaltered. The results illustrate that lipoprotein triacylglycerol levels can be modulated by changes in the availability of fatty acid substrate for triacylglycerol biosynthesis, mainly by affecting mitochondrial fatty acid oxidation. In addition, we demonstrate that suppression of rat hepatic HMG-CoA reductase activity during treatment with tetradecylthioacetic acid may contribute to a cholesterol-lowering effect.
Asunto(s)
Ácidos Grasos/metabolismo , Hígado/efectos de los fármacos , Hígado/metabolismo , Propionatos/farmacología , Sulfuros/farmacología , Triglicéridos/sangre , Triglicéridos/metabolismo , Animales , Colesterol/biosíntesis , Colesterol/metabolismo , Ésteres del Colesterol/biosíntesis , Lípidos/sangre , Lipoproteínas/sangre , Masculino , Oxidación-Reducción , Ratas , Ratas WistarRESUMEN
A practical procedure is described for the quantitative measurement of the amount of acyl units derived from tetradecylthioacetic acid (effecting hypolipemia in rats) and tetradecylthiopropionic acid (effecting hyperlipidemia). The procedure involves three main successive steps: (1) extraction; (2) solid-phase lipid class separation yielding free fatty acids, phospholipids, triacylglycerides, cholesterol esters, and diacylglycerides without crosscontamination; and (3) gas chromatography of hydrolyzed lipids derivatized to picolinyl esters, combined with unambiguous identification by gas chromatography-mass spectrometry. The overall recoveries of heptadecanoyl lipids added as internal standards during extraction were 94-96%, except for cholesteryl heptadecanoate where the recovery was 60% owing to incomplete hydrolysis. Recoveries of thia fatty acids from samples spiked with these compounds were 95%. Flame-ionization response factors were found to be 0.92 and 0.81 for the tetradecylthioacetic acid and tetradecylthiopropionic acid picolinyl esters, respectively, compared to that of heptadecanoic acid. The lower limit of quantitation was 25 pmol as injected. Measurement of the amount of thia fatty acyl units in rat plasma and in liver lipids 4 h after administration of single doses by gastric intubation indicated efficient absorbtion and rapid incorporation into liver lipids, particularly in the phospholipid fraction. Both plasma clearance and channelling into lipids was slower for the 4-thia fatty acid.
Asunto(s)
Cromatografía de Gases/métodos , Ácidos Grasos/análisis , Lípidos/análisis , Hígado/química , Propionatos/metabolismo , Sulfuros/metabolismo , Animales , Ácidos Grasos/sangre , Ácidos Grasos/metabolismo , Cromatografía de Gases y Espectrometría de Masas/estadística & datos numéricos , Cinética , Metabolismo de los Lípidos , Masculino , Propionatos/administración & dosificación , Ratas , Ratas Wistar , Sensibilidad y Especificidad , Sulfuros/administración & dosificaciónRESUMEN
This manuscript describes changes in plasma lipid profiles and parameters of oxidative status in the plasma and liver of rats fed 5 different fatty acids: 95% eicosapentaenoic acid, 92% docosahexaenoic acid (DHA), corn oil (n-6), 1-mono-(carboxymethylthio)-tetradecane (CMTTD) and palmitic acid (controls) for 3 months. At the given doses both EPA and the 3-thia fatty acid, CMTTD, caused a significant decrease in plasma triglycerides, phospholipids, free fatty acids and cholesterol. DHA decreased plasma free fatty acids and cholesterol, while corn oil feeding reduced only plasma free fatty acids. Plasma and hepatic vitamin E levels were significantly decreased in EPA, DHA and CMTTD fed rats, but remained unchanged in corn oil fed rats. Plasma glutathione was noted to decrease after EPA and DHA feeding but remained unchanged in other groups. However, hepatic glutathione content was increased in EPA, DHA and CMTTD fed rats, whereas cysteine levels were noted to decrease. As hepatic levels of cysteinylglycine remained unchanged, increased rate of cellular glutathione synthesis rather than its decreased degradation is likely to contribute to the increased hepatic glutathione content in EPA, DHA and CMTTD fed rats. Except for reduction in the levels of plasma lipid peroxidation caused by CMTTD, no significant changes were noted between the different treatment groups. Hepatic lipid peroxidation was elevated only in rats given DHA. Furthermore, our results show that EPA and DHA cause minimal imbalance of the peroxisomal H2O2 metabolising enzymes as compared to CMTTD. In addition, contrary to the potent peroxisome proliferator compound CMTTD which decreased the activities of glutathione transferase and glutathione peroxidase, EPA and DHA increased the activities of these detoxification enzymes.
Asunto(s)
Aceite de Maíz/farmacología , Aceites de Pescado/farmacología , Sulfuros/farmacología , Animales , Peso Corporal , Ácidos Docosahexaenoicos/farmacología , Ácido Eicosapentaenoico/farmacología , Metabolismo de los Lípidos , Peroxidación de Lípido , Lípidos/sangre , Hígado/enzimología , Masculino , Tamaño de los Órganos , Ratas , Ratas Wistar , Compuestos de Sulfhidrilo/metabolismo , Vitamina E/metabolismoRESUMEN
A single administration of 3-thiadicarboxylic and tetradecylthioacetic acids stimulates both mitochondrial and peroxisomal beta-oxidation and lowers plasma triacylglycerol levels. An increased rate of mitochondrial beta-oxidation and carnitine palmitoyl-transferase activity was established after 3 h and this was accompanied by a lowering of plasma triacylglycerol. Peroxisomal beta-oxidation, however, remained unchanged up to 8 h and was significantly increased after 12 h. These results suggest that after a single administration of 3-thia fatty acids mitochondrial beta-oxidation precedes peroxisomal beta-oxidation. Furthermore, they show that the observed tricylglycerol-lowering effect, which is established early (3-4 h) after the administration of 3-thia fatty acids, is initially due to an increased mitochondrial beta-oxidation.