RESUMEN
OBJECTIVE: The present study was designed to investigate the effects of dietary n-6 and n-3 lipids and exercise on the activities of hepatic antioxidant enzymes and microsomal lipid composition and peroxidation in Fischer-344 male rats. METHODS: Weanling male Fischer-344 rats were fed ad libitum semipurified diets containing 10% corn oil (CO) or 10% fish oil (FO), with equal levels of antioxidants. After 2 months on the diets, weight-matched animals in each diet group were divided into sedentary (S) and exercised (Ex) groups, and the diets were continued. The animals in the exercise group were run on a treadmill 30 to 40 minutes to exhaustion 6 days/week for 2 months. At the end of 2 months, the rats were sacrificed and livers were collected; antioxidant enzymes were determined in the cytosol, fatty acid composition was analyzed in the microsomes, and vitamin E levels were analyzed in the sera. RESULTS: The rats in the FO-S group exhibited significantly higher liver cytosolic catalase activity, while their superoxide dismutase (SOD) and glutathione peroxidase (GSH-Px) activities were significantly lower compared to the CO-S group. The GSH-Px activity was significantly higher in the FO-Ex group compared to FO-S group. The source of dietary lipids significantly influenced the fatty acid composition of the total lipids in the microsomes. Feeding the FO-based diet significantly increased 18:0 and n-3 fatty acids incorporation into the microsomes (18:3, 20:5, 22:5, and 22:6), whereas ingestion of CO resulted in a significant increase in 14:0, 14:1, 18:1, and n-6 fatty acids (18:2 and 20:4). The serum vitamin E levels were significantly higher in the CO groups, and exercise had no effect on vitamin E levels. Exercise significantly decreased the generation of thiobarbituric acid reactive substances (TBARS) by liver microsomes. Consumption of FO, which is highly susceptible to oxidation, did not show any significant changes in membrane lipid peroxidation. CONCLUSIONS: The present study suggests that feeding FO increases the activity of liver cytosolic catalase in FO-S rats and GSH-Px in FO-Ex rats. In addition, exercise significantly decreased the generation of TBARS by the liver microsomal lipids. Serum vitamin E levels were higher in the CO group and exercise did not alter vitamin E levels. This suggests that the amount of vitamin E included in the diets was possibly adequate to cope with the oxidative stress induced during exercise.
Asunto(s)
Antioxidantes/metabolismo , Grasas Insaturadas en la Dieta/farmacología , Ácidos Grasos Omega-3/farmacología , Ácidos Grasos Insaturados/farmacología , Hígado/enzimología , Esfuerzo Físico , Animales , Peso Corporal , Catalasa/metabolismo , Aceite de Maíz/administración & dosificación , Citosol/enzimología , Ácidos Grasos/análisis , Ácidos Grasos Omega-6 , Aceites de Pescado/administración & dosificación , Glutatión Peroxidasa/metabolismo , Peroxidación de Lípido , Lípidos/análisis , Masculino , Microsomas Hepáticos/química , Microsomas Hepáticos/metabolismo , Ratas , Ratas Endogámicas F344 , Superóxido Dismutasa/metabolismo , Vitamina E/sangre , DesteteRESUMEN
A new antiinflammatory agent identified as 8-[C-beta-D-[2-O-(E)-cinnamoyl]glucopyranosyl]-2- [(R)-2-hydroxypropyl]-7-methoxy-5-methylchromone (1) has been isolated from Aloe barbadensis Miller. At a dose of 200 microg/mouse ear, 1 exhibited topical antiinflammatory activity equivalent to 200 microg/ear of hydrocortisone. There was no reduction in thymus weight caused by treatment with 1 for any of the doses tested, while 200 microg/ear of hydrocortisone resulted in a 50% decrease in thymus weight.
Asunto(s)
Aloe/química , Antiinflamatorios no Esteroideos/aislamiento & purificación , Cromonas/aislamiento & purificación , Plantas Medicinales , Animales , Antiinflamatorios no Esteroideos/farmacología , Cromatografía Líquida de Alta Presión , Cromonas/farmacología , Aceite de Crotón , Oído Externo/patología , Cromatografía de Gases y Espectrometría de Masas , Inflamación/inducido químicamente , Inflamación/patología , Inflamación/prevención & control , Espectroscopía de Resonancia Magnética , Masculino , Espectrometría de Masas , Ratones , Ratones Endogámicos BALB C , Espectrofotometría UltravioletaRESUMEN
The fatty acid of acyl dihydroxyacetone phosphate can be exchanged enzymatically for another fatty acid. It has been shown that this reaction proceeds by cleavage of the oxygen bound to C-1 of the dihydroxyacetone phosphate (DHAP) moiety rather than by the more common cleavage at the acyl to oxygen bond. In the present study, the stereochemistry of this reaction was defined further; using deuterated substrates and fast atom bombardment-mass spectrometry, it was shown that the fatty acid exchange involves the stereospecific labilization of the pro-R hydrogen at C-1 of the DHAP moiety of acyl DHAP. The mechanism of ether bond formation, in which acyl DHAP is converted to O-alkyl DHAP, also proceeds via labilization of the pro-R hydrogen and cleavage of the fatty acid at the C-1 to oxygen bond. In addition, other workers have provided evidence that the enzyme responsible for the exchange reaction is O-alkyl DHAP synthetase. Therefore, the present results support the hypothesis that the acyl exchange is the reverse reaction of the first step in O-alkyl DHAP synthesis; in both of these reactions the pro-R hydrogen of C-1 of the DHAP moiety of acyl DHAP and the fatty acid moiety are labilized with cleavage of the fatty acid at the DHAP C-1 to oxygen bond.
Asunto(s)
Dihidroxiacetona Fosfato/química , Dihidroxiacetona/análogos & derivados , Dihidroxiacetona/química , Dihidroxiacetona Fosfato/metabolismo , Ácidos Grasos/química , Hidrógeno/química , Conformación Molecular , Espectrometría de Masa Bombardeada por Átomos VelocesRESUMEN
Methods are detailed for the preparation of [2-18O]glycolate from chloroacetic acid and for the direct conversion of these intermediates to regiospecifically labeled [2-18O]-2-O-acylglycolic acids containing approximately 90% 18O at the C-O-acyl bond. Methods are also detailed for optimization of reaction conditions and yields for each synthetic step in previously published methods for the preparation of 1-O-acyldihydroxyacetone-3-O-phosphate (DHAP) from acyloxyacetic acid (i.e., 2-O-acylglycolic acid), where acyl is tetradecanoyl, hexadecanoyl, or heptadecanoyl. The optimized reaction conditions generate 1-O-acyl DHAP in its acid form, both in high overall yield and in high purity, without requiring a final chromatographic purification of the product, 1-O-acyl DHAP. Combining these new methods, efficient and facile preparations of regiospecifically labeled [1-18O]-1-O-hexadecanoyl DHAP and [1-18O]-1-O-heptadecanoyl DHAP have now been demonstrated, in which approximately 90% 18O is specifically located only at the C-O-acyl position. Some mechanistic postulates are offered to account for the optimized yields, regioselectivities, and high 18O incorporation which are observed in the reactions we have employed to generate 1-O-acyl DHAP from glycolate intermediates.
Asunto(s)
Dihidroxiacetona Fosfato/análogos & derivados , Dihidroxiacetona Fosfato/síntesis química , Dihidroxiacetona/síntesis química , Glicolatos/síntesis química , Triosas/síntesis química , Dihidroxiacetona/análogos & derivados , Espectrometría de Masas , Isótopos de OxígenoRESUMEN
We have previously provided evidence for a mechanism by which acyl DHAP is converted enzymatically to O-alkyl DHAP. This mechanism involves, in part, the formation of an endiol of acyl DHAP, loss of the fatty acid by splitting of the DHAP carbon-1 to oxygen bond and the gain of a long chain fatty alcohol. It has been shown that acyl DHAP can exchange its fatty acid for one in the medium, presumably by the mediation of O-alkyl DHAP synthase. In the present investigation we have shown that the fatty acid which is gained by acyl DHAP in the exchange process retains both carboxyl oxygens, as predicted by our postulated mechanism. This reaction is exceptional because the usual action of acyl hydrolases is to cleave at the oxygen to acyl bond.