The Contribution of cocoa additive to cigarette smoking addiction

RIVM report 650270002 Page 83 of 207
Histamine
undergoes significant N-methylation to produce N-methylnicotinium ion. S-(-)-
Nicotine appears to inhibit the N-methylation of its optical antipode by the alveolar
nicotine N-methyltransferase. The results indicate that a contributing factor in the
toxicology of cigarette smoke inhalation may be due to the inhibition of pulmonary
metabolism of histamine by nicotine (56).
In vitro studies with rat intestines showed that the potentiation of histamine toxicity
by putrefactive amines, such as cadaverine, results from the inhibition of histamine
metabolism which leads to increased uptake of unmetabolized histamine (57).
The airway response to histamine has been shown to be related to the 24 hour urinary
excretion of sodium. To assess whether this relation is likely to represent a direct
causal association a randomised double blind crossover trial of slow sodium (80
mmol/day) was compared with placebo in 36 subjects having a low sodium diet. The
dose of histamine causing a 20% fall in FEV1 (PD20) was 1.51 doubling doses lower
when the men were taking sodium than when they were taking placebo (p less than
0.05). On the basis of PD10 values, the difference in men was 1.66 doubling doses of
histamine (p less than 0.05). There was no corresponding effect in women.
Regressing PD10 against urinary excretion of electrolytes with data from the two
occasions during the trial and the measurements made before the trial showed a
significant association with sodium excretion after allowance had been made for any
effect associated with potassium or creatinine excretion, the latter being a marker of
the completeness of the urine collection. Again there was no corresponding effect
among women. These findings are compatible with the differences in regional
mortality data for England and Wales, which show a relation between asthma
mortality and regional per person purchases of table salt for men but not for women
(58).
Critical assessment
Chemical (see critical assessment of the general section)
The free amino group is
a potential group to react with aldehydes and ketones and with monoaminooxydase
(MOA);
a base group, i.e. a potential group to react with acids.
The ring nitrogen atoms:
The extra pairs of electrons are involved in the pi-cloud of the ring and are not
available for sharing with acids.
Substitution reactions may occur in which the stabilized ring is retained.
In vivo
Histamine level in the body is increased either by mediators (at food allergy) or by
inhibition of the histamine metabolism (by nicotine or putrefactive amines).
Increased sodium intake seems to increase the hyperresponsiveness to histamine
reactions in asthmatic men. It is unclear whether histamine increases the permeability
of the respiratory mucosa to other compounds.
Conclusion
Chemical
Especially the free amino group has the potential of a reactive site.