6-ketoprostaglandin-f1-alpha and propionylcarnitine

The effect of short- and long-term feeding with L-carnitine, L-acetyl carnitine and L-propionyl carnitine on the production of eicosanoids from in vitro stimulated carrageenan-induced rat peritoneal macrophages was investigated. Both young (4 weeks) and old (18 months) rats were used. A lower number of cells was isolated from the peritonea of treated than control young rats after 4 d feeding, but after 60 d no differences were observed. A similar reduction in cell number was found when old animals were given L-acetyl carnitine or L-propionyl carnitine (acutely) or L-acetyl carnitine or L-carnitine (chronically). Plasma carnitine levels were higher in young rats given carnitine both chronically and acutely. Carnitine derivatives were without effect. In contrast, levels of total carnitine in the plasma of old rats given L-carnitine and L-acetyl carnitine for 4 d and 60 d were higher than in controls. There was no correlation between total plasma carnitine level and effects on prostaglandin, thromboxane and leukotriene B4 (LTB4) production. In young rats the most important changes were observed in relation to the production of prostacyclin (PGI2), measured as 6 keto-prostaglandin F1 alpha. Prostacyclin production was higher in the groups given carnitine or its derivatives. The net result of the changes in PGI2 was that the 6 keto-prostaglandin F1 alpha: thromboxane B2 and the 6-keto-prostaglandin F1 alpha: LTB4 ratios tended to be higher in cells from young animals following short-term feeding with L-carnitine.(ABSTRACT TRUNCATED AT 250 WORDS)

Topics: 6-Ketoprostaglandin F1 alpha; Acetylcarnitine; Animals; Carnitine; Cell Count; Eicosanoids; In Vitro Techniques; Leukotriene B4; Macrophages, Peritoneal; Male; Rats; Rats, Wistar; Time Factors

Little is known about the ability of carnitine to modulate cell functions. As carnitine plays an important role in lipid metabolism we investigated the acute effect of L-carnitine, L-acetyl carnitine and L-propionyl carnitine (300 mg/kg per d; 4 d) on the basal and calcium-ionophore (A23187)-stimulated release of arachidonic acid metabolites from rat carrageenan-elicited peritoneal macrophages. A decrease in the number of peritoneal carrageenan-elicited macrophages was observed after feeding all three compounds. The basal release of prostaglandin E2, 6 keto-prostaglandin F1 alpha and leukotriene B4 was stimulated by all treatments. In contrast, thromboxane B2 production was diminished by feeding carnitine and acetyl carnitine. A23187-stimulated synthesis of 6 keto-prostaglandin F1 alpha and leukotriene B4 was further enhanced by all three compounds. Acetyl carnitine and propionyl carnitine also enhanced thromboxane B2 synthesis. However, no effects on prostaglandin E2 formation were detected. The 6 keto-prostaglandin F1 alpha:thromboxane B2 ratio, calculated from the basal and A23187-stimulated values, was increased by carnitine treatment. In the presence of A23187 there was also an increase in the 6 keto-prostaglandin F1 alpha:leukotriene B4 ratio. We conclude that carnitine, and possibly some of its derivatives, could modify the macrophage component of an inflammation in vivo.

Topics: 6-Ketoprostaglandin F1 alpha; Acetylcarnitine; Animals; Calcimycin; Carnitine; Dinoprostone; Eicosanoic Acids; Leukotriene B4; Macrophages; Male; Rats; Rats, Inbred Strains; Thromboxane B2