The Role of Histamine in Radiation

Toxic Effects .
Part 1.
Dmitri Popov. PhD, Radiobiology. MD
(Russia)
Advanced Medical Technology and Systems
Inc. Canada.

The Role of Histamine in

Radiation Toxic Effects .
A biogenic amine is a biogenic substance with

one or more amine groups. They are

basic nitrogenous compounds formed mainly
by decarboxylation of amino acids or
byamination and transamination of aldehydes and
ketones. Biogenic amines are organic bases with
low molecular weight and are synthesized by
microbial, vegetable and animal metabolisms. In
food and beverages they are formed by the
enzymes of raw material or are generated by
microbial decarboxylation of aminoacids.
http://en.wikipedia.org/wiki/Biogenic_amine

The Role of Histamine in

Radiation Toxic Effects .
Classical monoaminesHistamine - a substance

derived from the amino acid histidine that acts as

a neurotransmitter mediating arousal and attention, as
well as a pro-inflammatory signal released from mast
cells in response to allergic reactions or tissue
damage. Histamine is also an important stimulant of
HCl secretion by the stomach through histamine
H2 receptors.
Serotonin - a central nervous system neurotransmitter
derived from the amino acid tryptophan involved in
regulating mood, sleep, appetite, and sexuality.
http://en.wikipedia.org/wiki/Biogenic_amine

The Role of Histamine in

Radiation Toxic Effects .
Histamine is an organic nitrogenous compound

involved in local immune responses as well as

regulating physiological function in the gut and acting
as a neurotransmitter. Histamine is involved in
the inflammatory response. As part of an immune
response to foreign pathogens or physical agents
such as radiation histamine is produced
by basophils and by mast cells found in nearby
connective tissues. Histamine increases the
permeability of the capillaries to white blood cells and
some proteins, to allow them to engage pathogens in
the infected tissues.
http://en.wikipedia.org/wiki/Biogenic_amine

The Role of Histamine in

Radiation Toxic Effects .
Histamine is derived from the decarboxylation of

the amino acid histidine, a reaction catalyzed by

the enzyme L-histidine decarboxylase. It is
a hydrophilic vasoactive amine.
http://en.wikipedia.org/wiki/Histamine

The Role of Histamine in

Radiation Toxic Effects .
Most histamine in the body is generated in granules
in mast cells and in white blood cells
called basophils and eosinophils. Mast cells are
especially numerous at sites of potential injury
the nose, mouth, and feet, internal body surfaces,
and blood vessels. Non-mast cell histamine is
found in several tissues, including the brain,
where it functions as a neurotransmitter. Another
important site of histamine storage and release is
the enterochromaffin-like (ECL) cell of
the stomach.

The Role of Histamine in

Radiation Toxic Effects .
The most important pathophysiologic mechanism

of mast cell and basophil histamine release

is immunologic. These cells, if sensitized by
IgE antibodies attached to
their membranes, degranulate when exposed to
the appropriate antigen.
Certain amines and alkaloids, including such
drugs as morphine, and curare alkaloids, can
displace histamine in granules and cause its
release. Antibiotics likepolymyxin are also found
to stimulate histamine release. RADIATION can
also stimulate histamine release.

The Role of Histamine in

Radiation Toxic Effects .
Histamine release occurs when allergens bind to

mast-cell-bound IgE antibodies. Reduction of IgE

overproduction may lower the likelihood of
allergens finding sufficient free IgE to trigger a
mast-cell-release of histamine.
How radiation can play a role of allergens and

trigger a mast-cell-release of histamine.

The Role of Histamine in

Radiation Toxic Effects .
Histamine H1receptor.

CNS: Produced in the tuberomamillary nucleus,

projecting to thedorsal raphe, locus coeruleus,

and either to and/or through thehippocampal
formation, amygdala, basal
ganglia, thalamus, superior colliculus,
and cerebellum
PNS: Smooth muscle and endothelium

The Role of Histamine in

Radiation Toxic Effects .
CNS: sleep-wake cycle, body

temperature, nociception, endocrine

homeostasis,appetite, mood, learning,
and memory
PNS: Causes bronchoconstriction,
bronchial smooth muscle contraction,vasodilation,
separation of endothelial cells (responsible
for hives), and pain and itching due to insect
stings; the primary receptors involved in allergic
rhinitis symptoms and motion sickness

The Role of Histamine in

Radiation Toxic Effects .
Histamine H2receptor.

Located on parietal cells and vascular smooth

muscle cells. Primarily involved in vasodilation.

Also stimulate gastric acid secretion.
Histamine H3receptor. Found on central nervous
system and to a lesser extent peripheral nervous
system tissue,
Decreased neurotransmitter release:
histamine, acetylcholine, norepinephrine,
serotonin

The Role of Histamine in

Radiation Toxic Effects .
Histamine H4receptor. Found primarily in

the basophils and in the bone marrow.

It is also found on thymus, small
intestine, spleen, and colon.
Plays a role in mast cell chemotaxis.

The Role of Histamine in

Radiation Toxic Effects .
Tissue mast cells, which have been traditionally

studied in the context of post-radiation allergic

inflammation , are not well studied and remain
controversial to play a role in activation both innate
and acquired immunity after irradiation.

The Role of Histamine in

Radiation Toxic Effects .
A qualitative risk assessment of biogenic amines

(BA) after irradiation in blood, lymph and tissues

was conducted, using data from the scientific
literature, as well as original research studies
conducted .
Histamine and serotonin are considered as the
potentially toxic substances after irradiation.
Concern due to associated intensive irradiation
and enzyme activity and potential for immune
system toxic and autoimmune response with auto
antibodies and Biogenic Amines formation.

The Role of Histamine in Radiations

Toxic Effects.
Scombroid fish poisoning (often called "histamine

poisoning") is caused by ingestion of certain

species of marine fish that contain high levels of
histamine and possibly other biogenic amines.
These fish species contain high levels of free
histidine in their tissue and when such fish are
subjected to temperature abuse after harvest,
bacteria decarboxylate histidine to produce
histamine. A number of bacterial species can
produce histamine, but Morganella
morganii and Proteus spp. are particularly strong
histamine producers.

The Role of Histamine in

Radiation Toxic Effects .
Histamine playing important role in food toxicity.
Histamine is an organic nitrogen compound that

may trigger an allergic response in human and

mammalian systems. Other biogenic amines
(such as cadaverine and putrescine) are thought
to potentiate the toxic effect of histamine.
Although fatal cases are rare, severity of the
symptoms can vary depending on the amount of
histamine and other biogenic amines ingested
and the individuals sensitivity to specific biogenic
amines. WHO
http://www.who.int/foodsafety/histamine/en/

The Role of Histamine in

Radiation Toxic Effects .
Scombroid fish poisoning (often called "histamine

poisoning") is caused by ingestion of certain species

of marine fish that contain high levels of histamine
and possibly other biogenic amines. These fish
species contain high levels of free histidine in their
tissue and when such fish are subjected to
temperature abuse after harvest, bacteria
decarboxylate histidine to produce histamine. A
number of bacterial species can produce histamine,
but Morganella morganii and Proteus spp. are
particularly strong histamine producers.
http://www.who.int/foodsafety/histamine/en/

The Role of Histamine in

Radiation Toxic Effects .
Eating food (fish particularly) with high levels of

histamine can result in Histamine Fish Poisoning.

HFP
The symptoms of HFP can be very similar to
severe allergic reactions which can happens
within minutes to hours after ingestion of toxic fish
with high levels of Histamine in tissue.
Symptoms of Histamine poisoning include:
A burning/tingling sensation around of mouth.
Rush and or swelling over the chest and\or neck.

The Role of Histamine in

Radiation Toxic Effects .
Lowering of blood pressure.
Headache..
Itchy skin, vomiting, diarrhea.
Symptoms of irradiation:
The prodrome (early symptoms) of Acute Radiation

Syndrome typically includes nausea and vomiting,

headaches, fatigue, fever and short period of skin
reddening. These symptoms may occur at radiation
doses as low as 35 rad (0.35 Gy). These symptoms
are common to many illnesses (Include HFP) and
may not, by themselves, indicate acute radiation
sickness.

The Role of Histamine in

Radiation s Toxic Effects .
The role of Histamine in development of Radiation s toxic

effects remain very controversial and need to be

reconsidered.
1. Scientists reported that histamine and biogenic amines
playing extremely active role in development pathophysiological consequences after irradiation.
http://www.intechopen.com/books/current-topics-inionizing-radiation-research/radiation-toxins-molecularmechanisms-of-toxicity-and-radiomimetic-propertiesRadiation Toxicity: A Practical Medical Guide
edited by William Small,, Gayle E. Woloschak.
2. Scientists reported that histamine and biogenic amines
dont play any role in development patho-physiological
consequences and clinical signs after irradiation.

The Role of Histamine in

Radiation Toxic Effects .
3. Scientists reported that histamine and biogenic amines

playing extremely active role in development

Radioprotective mechanisms after irradiation.
Histamine prevents radiation-induced toxicity by
increasing proliferation of damaged intestinal mucosa and
suppressing apoptosis that was associated with an
increase in SOD and Catalase levels. This effect might be
of clinical value in patients undergoing radiotherapy. Int J
Radiat Biol. 2007 Oct;83(10):653-63.
Mechanisms underlying the radioprotective effect of
histamine on small intestine.
Medina VA1, Croci M, Mohamad NA, Massari N, Garbarino
G, Cricco GP, Nez MA, Martn GA, Crescenti EJ, Bergoc
RM, Rivera ES.

The Role of Histamine in

Radiation Toxic Effects .
Part 2 under way.