EFFECTS OF SHORT-TERM AND LONG-TERM FEEDING OF L-CARNITINE AND CONGENERS ON THE PRODUCTION OF EICOSANOIDS FROM RAT PERITONEAL LEUKOCYTES

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 B-4 (LTB(4)) production. In young rats the most important changes were observed in relation to the production of prostacyclin (PGI(2)), measured as 6 keto-prostaglandin F-1 alpha. Prostacyclin production was higher in the groups given carnitine or its derivatives. The net result of the changes in PGI(2) was that the 6 keto-prostaglandin F-1 alpha:thromboxane B-2 and the 6 keto-prostaglandin F-1 alpha:LTB(4) ratios tended to be higher in cells from young animals following short-term feeding with L-carnitine. When young rats were given carnitine compounds for 60 d PGI(2) production was lower in cells from L-acetyl carnitine- and L-propionyl carnitine-fed animals. The net result of the changes in PGI(2) was that the 6 keto-prostaglandin F-1 alpha:thromboxane B-2 and the 6 keto-prostaglandin F-1 alpha:LTB(4) ratios were lower in cells from animals fed with carnitine compounds. In old rats the PGI, production was lower after short-term feeding with carnitine compounds and was higher after long-term feeding. LTB, production was lower after L-carnitine and L-acetyl carnitine treatment for 4 d and also lower after 60 d treatment with L-acetyl carnitine. The net results of the changes in PGI, were that the 6 keto-prostaglandin F-1 alpha:thromboxane B-2 and the 6 keto-prostaglandin F-1 alpha:LTB(4) ratios were lower after short-term feeding of all three compounds and higher after the long-term treatment with L-acetyl carnitine and L-propionyl carnitine in old rats. By long-term treatment with low-dose aspirin of patients with heart failure and claudication, the 6 keto-prostaglandin F-1 alpha:thromboxane B-2 ratio is positively increased, which is a beneficial cardioprotective effect. The mechanism of action of carnitine in heart failure and claudication could also be achieved by an increase of this ratio. Our results suggest that elderly patients could be treated chronically by carnitine to obtain this beneficial effect.