The Contribution of cocoa additive to cigarette smoking addiction

Page 58 of 207 RIVM report 650270002
Serotonin
Critical assessment
The serotonin toxicity is observed by elevated local or systemic serotonin level, that
is induced by several exogenous agents or by carcinoid tumor. Several pathologies
are related to the increased serotonin level. No toxicity data on the effects of
serotonin administered through inhalation are available. It is unlikely that exposure to
serotonin through smoking leads to systemic serotonin levels that exert
toxicologically relevant effects.
Conclusion
Since no data on the toxicological effects of serotonin exposure through inhalation
are available, the influence of exposure to serotonin through smoking on the
respiratory system cannot be established. Given the high endogenous serotonin levels
as compared to the exposure via smoking, it is unlikely that systemic effects will be
induced.
INTERACTIONS
Chemical
One-electron oxidation of serotonin with N-3(.) and Br-2(.) radicals resulted in the
formation of an indoloxyl radical with a pK(a) value much less than 3. The reactions
of OH radicals ((OH)-O(.)) with serotonin lead to the formation of (OH)-O(.)adducts,
which decay by acid catalyzed water elimination to give almost
quantitatively the corresponding indoloxyl and indolyl radicals, respectively. The
first-order rate constants determined for water elimination are pH dependent,
suggesting that the dehydration reaction is acid and base catalyzed. The (OH)-O(.)adduct
of serotonin reacts with oxygen in competition with the dehydration reaction
to yield a peroxyl radical adduct, which is tentatively suggested to eliminate HO2(.).
On the basis of the above findings, the mechanisms for the (OH)-O(.)-induced
formation of indoloxyl from serotonin is proposed (46).
In vivo
Numerous agents affect the serotonin level in the body, by inhibition of tryptophan or
serotonin metabolism and by inhibition of serotonin re-uptake in the presynaps.
Fructose malabsorption is associated with lower tryptophan levels that may play a
role in the development of depressive disorders. High intestinal fructose
concentration seems to interfere with L-tryptophan metabolism, and it may reduce
availability of tryptophan for the biosynthesis of serotonin (47).The effect of changes
in chronic protein intake on plasma and cerebrospinal fluid (CSF) concentrations of
tryptophan and 5-hydroxyindoleacetic acid (5HIAA), the principal serotonin
metabolite, was studied in monkeys. The variation in CSF 5HIAA suggested that
chronic protein intake may influence serotonin synthesis and turnover, perhaps via
changes in tryptophan concentrations (26). Ethanol and food (banana) affect the
metabolic pathway of serotonin. The urinary excretion products of serotonin are 5hydroxyindole-3-acetic
acid (5HIAA) and 5-hydroxytryptophol (5HTOL), and the
ratio of 5HTOL to 5HIAA is normally very low (< 0.01) in man. During metabolism
of ethanol there is a shift in the catabolic pattern of serotonin, and the formation of
5HTOL increases appreciably at the expense of 5HIAA. This increased is more
pronounced with concomitant intake of serotonin rich food (3 –4 bananas) and
unpleasant symptoms symptoms (diarrhea, headache, and fatigue) are observed,
which are associated with the serotonin system (11).
Inhibition of serotonin metabolism or inhibition of serotonin re-uptake in the synaps