Tryptophan metabolism via serotonin in rats with hexachlorobenzene experimental porphyria

One of the three pathways for the metabolisation of dietary tryptophan is the formation of serotonin. Tryptophan hydroxylase catalyses the formation of 5-hydroxytryptophan, the first and regulatory step of this biosynthesis. The aim of the present work is to study alterations in this tryptophan metabolism in rats with experimental Porphyria Cutanea Tarda induced by hexachlorobenzene. With this purpose, the content of tryptophan and its metabolites related to the serotonin pathway are determined by HPLC techniques, in tissues (brain, liver and gut) and in fluids (blood, plasma and urine) of controls and hexachlorobenzene-porphyric rats. In these experimental-porphyric animals, we determine a significant increase in the excretion of 5-hydroxyindole acetic acid in urine and a decrease in the content of serotonin in small gut, respect to controls. Significant increases in contents of serotonin in 24-hr urine and tryptophan in liver are also found. No other significant variations for the different metabolites are detected in any of the tissues and fluids studied. Brain and liver activities of the rate-limiting enzyme tryptophan hydroxylase can only be measured in porphyric rats. Our results agree with an increased turnover of gastrointestinal serotonin derived from dietary tryptophan and its excretion as urinary 5-hydroxyindole acetic acid, which is formed in liver. An increased serotonin pathway in porphyric livers is confirmed by the measured increase in the activity of hepatic tryptophan hydroxylase. The absence of neurological symptoms in patients with Porphyria Cutanea Tarda could be related to the absence of a statistically significant variation in serotonin content shown in brain.