Kinetics of dodecanedioic acid and effect of its administration on glucose kinetics in rats

Abstract

Dodecanedioic acid (C12), a saturated aliphatic dicarboxylic acid with twelve C atoms, was given as an intraperitoneal bolus to male Wistar rats, with the aim of evaluating C12 suitability as an energy substrate for parenteral nutrition. The 24 h urinary excretion of C12 was 3·9% of the administered dose. C12 kinetics were investigated by a one-compartment model with saturable tissue uptake and reversible binding to plasma albumin. The analysis of plasma concentration and urinary excretion data from different animals yielded the population means of the kinetic parameters: renal clearance was 0·72ml/min per kg body weight (BW) (much smaller than inulin clearance in the rat), and maximal tissue uptake was 17·8 μmol/min per kg BW corresponding to 123·7 J/min per kg BW. These results encourage the consideration of C12 as a possible substrate for parenteral nutrition. To investigate the effect of C12 administration on glucose kinetics, two other groups of rats, one treated with an intraperitoneal bolus of C12 and the other with saline, were subsequently given an intravenous injection of D-[U-14C]glucose in a tracer amount. Radioactivity data of both control and C12-treated rats were analysed by means of a two-compartment kinetic model which takes into account glucose recycling. The estimates of glucose pool size (2·3 mmol/kg BW) and total-body rate of disappearance (82·1 μmol/min per kg BW) in control rats agreed with published values. In C12-treated rats, the rate of disappearance appeared to be reduced to 36·7 μmol/min per kg BW and the extent of recycling appeared to be negligible.