Relationships between methoxyindole and kynurenine pathway metabolites in plasma and urine in children suffering from febrile and epileptic seizures

Abstract

Our results point to the existence of an imbalance in the tryptophan metabolite pathways during convulsions, blunting the normal diurnal-nocturnal rhythm of kynurenines. They also support the idea of a difference in the production of tryptophan metabolites between febrile and epileptic patients, suggesting that the tryptophan pathways follow different routes depending upon the type and duration of the convulsion.

Comparison between tryptophan methoxyindole and kynurenine metabolic pathways in normal and preterm neonates and in neonates with acute fetal distress

“…At night, tryptophan degradation would occur via the methoxyindoles, thus explaining increased nocturnal melatonin concentrations whereas, during the day, because production of melatonin would not be necessary, degradation of the amino acid precursor would take place via the kynurenine pathway. The tryptophan metabolic disorders studied here and those reported elsewhere (34) suggest that the changes in the tryptophan metabolic pathways may be attributable to a so-called 'enzymatic gate' mechanism, in which the substrate is used according to the factors regulating it. Under situations of acute stress such as fetal distress or convulsions, the melatonin pathway would predominate, because of its known antistress and neuroprotective effect (43).…”

“…This equilibrium is lost under conditions of stress (5,6,34,36), and the degree of deviation depends on both the type of stress experienced and the patient. Two types of neonatal stress, prematurity and fetal distress, were studied here.…”

“…Under situations of acute stress such as fetal distress or convulsions, the melatonin pathway would predominate, because of its known antistress and neuroprotective effect (43). Once the crisis is overcome, the pathways would readjust and the initial situation be restored (34).…”

“…These metabolites were determined by thin-layer chromatography (TLC) described elsewhere (33,34), using 60 F254 silica gel plates (Merck, Madrid, Spain). Briefly, 20 ml standard mixture containing 4 mg each standard or 100 ml urine were applied to the chromatographic plate and quickly dried to avoid diffusion of the sample.…”

“…The chromatographic method was highly sensitive, even when there were marked concentration variations among the five metabolites studied. The TLC method was subject to quality control (34). Within-run (withinplate) analytical variation for the kynurenine standards of eight replicates at every concentration of each metabolite was determined, and the coefficients of variation thus obtained were between 6.5% and 8.5%.…”