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 Radiation’s 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 individual’s 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 patho-physiological consequences after irradiation. http://www.intechopen.com/books/current-topics- in-ionizing-radiation-research/radiation-toxins-molecular-mechanisms- of-toxicity-and-radiomimetic-properties- Radiation Toxicity: A Practical Medical Guide  edited by William Small,, Gayle E. Woloschak. 2. Scientists reported that histamine and biogenic amines don’t 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, Núñez MA, Martín GA, Crescenti EJ, Bergoc RM, Rivera ES.

The Role of Histamine in Radiation’ Toxic Effects . Part 2 under way.