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Allergic and Toxic Responses of Insect Venom and It's Immunotherapy

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Allergic and Toxic Responses of Insect Venom and It's Immunotherapy Review Article Ravi Kant Upadhyay et al. / Journal of Pharmacy Research 2010, 3(12),3123-3128 ISSN: 0974-6943 Available online through http://jprsolutions.info Allergic and toxic responses of insect venom and it’s immunotherapy Ravi Kant Upadhyay*, Shoeb Ahmad Department of Zoology, D D U Gorakhpur University, Gorakhpur, 273009. India Received on:06-08-2010; Revised on: 18-09-2010; Accepted on:12-11-2010 ABSTRACT Insect venom is a poisonous substance that contains a complex mixture of certain proteins, enzymes, small peptides, certain inorganic elements and acids. These venom components are responsible for multiple pharmacological effects in different organisms and act like toxins. These act at cellular level and break the normal barrier to leak out molecules across the cell membrane and form ion channels by attaching themselves to the membrane surface. Venom allergens cause immuno- stimulation of body tissues and show strong T cell responses in hypersensitive patients and signify the production of allergen specific IgE antibodies and generate anaphylactic reactions.. These also trigger a cascade of mediators including histamine, leucotrienes, and platelet activating factors, enzymes and peptides. Venom toxins make fast release of certain chemicals i.e. serotonins, kinins, prostaglandins and leukotrienes that results in visible clinical symptoms related to paralysis, inflammation, swelling and itching. Insect venom toxins elevate the level of blood sugar, lactate, glucagon and cortisol and cause massive destruction of RBCs and nerve cells. Besides this, insect venom possess highly potent short peptides, which act upon ion channels of excitable cells and inhibit the activity of important metabolic enzymes like ACP ALP, GPT, GOT, LDH, AChE and Creatinine phosphokinase. Melittin is a short peptide that shows cytotoxicity and cause intra- vascular hemolysis of RBCs, leucocytes, platelets and vascular endothelium. It is highly basic peptide that inserts itself into the phospholipid bi-layer of cell membranes. It in conjugation with PLA2 causes active pancreatitis and rhabdomyolysis in patients. Indeed, it appears that peptide toxins are strong ion channel blockers, which selectively act on various ion channels. This review aims to emphasize use of toxin specific immunoglobulins in immunotherapy of patients to detoxify the effect of venom toxins. Immunotherapy contributes to decrease the number of mast cells, do activation of eosinophils, and induce T cell tolerance to the venom allergens. It subside the toxic effects of venom toxins and much ably revert the enzyme activity. Key words: Insect venom, allergy, honeybee, toxic responses, sting, immunotherapy INTRODUCTION Arthropods mainly insects such as honeybee (Apis) (Edstrom, 1992, Dotimas VENOM COMPOSITION et al., 1987), social wasps (Vespula, Vespa, and Polistes), Paper wasps, hornets Arthopods mainly Apis, Bombus, Xilocopa, Vespula, Dolichovespula, and (Hoffman, 1996) and some ant species (Blum, 1978) possess venom glands Polistes species possess pharmacologically different types of venom toxins and discharge them to make territorial defense (Hider,1988;Blum,1981). These (Hoffman and Jacobson 1984) with diverse function and structural composi- insects after sensing little disturbance with in the territory and foraging sites tion (Blum, 1981, Lindsay and Bashford, 2001; Siphadauang and Noga, 2001). (Reisman, 1994), start searching the nuisance element and inflict toxic venom Their mechanism of action is unique causing electro-physiological inhibition into the body of victim (Nabil et al., 1998). Venom is inflicted by using of various ionic channels in nerve cell membrane (Schmid-Antomarchi et al., specialized sting apparatus attached with venom gland found in the last seg- 1985). These contain a number of charged residues including several positively ment of body. Stinging is a natural defense mechanism that is very swift and charged amino acids, which are biologicaly active (Hawgood and Bon, 1991). occurs almost instantaneously (Dotimas and Hider, 1987). It is triggered by Pharmacologically, insect venoms are a rich source of biologicaly different pheromone secretion after alarming (Hider, 1988). It is highly painful (Mietka- molecules such as alkaloids, terpenes, polysaccharides, biogenic amines (His- Ciszowski 2007) and provokes allergic and toxic reactions in the patients tamine) and organic acids, but the majority of them are peptides and proteins (Golden, 2006). It shows reflex action in the muscles (Hermann, 1971), do (Schmidt, 1986). Venom of Apis species is a mixture of biogenic amines such immobilization of invaders or predators (Frazier, 1976) and causes itching, as histamine, serotonin, dopamine, noradrenaline, apamin, melittin and phos- swelling, redness, irritation in human skin and headache in patients. On an pholipase A2 (Table 2) (Wongsiri et al., 1987) and shows compositional simi- average 8 out of 1000 individuals show allergic reactions to sting and 4 of larities to social wasp venom, especially to Vespula, Vespa and Polistes genera these i. e. 50% become severely sensitive (Frazier, 1976). Besides insects, (Nakazima, 1986). Apis mellifera venom contains low molecular weight com- scorpion and spiders utilize venom toxins for self-defense and hunting the ponents such as serotonin, histamine, acetylcholine, several kinins, enzymes prey (Fitzgeralg and Flood, 2006; Benton, et al., 1963). However, multiple phospholipase A2 and hyaluronidase, polypeptides such as melittin and apamin insect stings cause anaphylaxis, dyspnea, collapse, rhabdomyolysis and pig- and mast cell degranulating pepetides. Wasp venom lacks serotonin and adrena- ment induced acute renal failure and severe pancreatitis. Insect venom causes line amongst biogenic amines (Banks and Shipolini, 1986) while ant venom respiratory distress syndrome (Franca et al, 1994). Heavy envenomation in contains simple organic acids and complex mixture of proteins and enzymes. groups causes obstruction of respiratory tube that contributes hypoxia and It causes allergy, inflammation, itching and show toxic responses in mammals respiratory failure in patients. If timely treatment is not provided to such (Fundenberg et al., 1980). Bee venom contains melittin peptide that provokes patients it results in death of the victim (Schmacher and Egen 1995, Mckenna allergic reactions (Table 2) (Fennel et al., 1968). Similarly, hornetin a highly 1992, Tungent and Clark 1993). Insect venom show very high proteolytic basic protein isolated form Vespa flavitarsus shows hemolytic activity in red activity (Hoffaman and Jacobson 1996) and exhibit coagulant, fibrinolytic blood cells and damage presynaptic nerve cells (Ho and Ko, 1986). Besides (Koh et al, 2001; Mackessy 1996) and hemorrhagic activities (Bjarnheimer this, few venom enzymes such as phospholipases, hyaluronidase, and acid and Fox 1994, Mackessy 1996). Bee venom causes hyperglycemia (Scheuer et phosphatase also act as allergens (Tonismagi et al., 2006). Contrary to this al, 1969), liver and muscle necrosis and elevate the serum enzyme activity Vespula maculifrons, Vespula maculate, and Vespula arenaria venom protiens (Tunget and Clark 1993). Venom components mainly melittin shows cyto- show different allergic reactions due to presence of phospholipase A1B, hyalu- toxicity (hemolysis) while apamin act as neurotoxin. In addition to it mast ronidase and some other allergenic compounds (Mueller et al., 1982). Inter- cell degranulating peptides show anaphylactic reactions. Besides this, enzymes estingly, insect venom is a pool of allergic and toxic peptide and enzymes, like phospholipase A2 causes acute pancreatitis and do pulmonary failure. It is which show diverse arrays of biological activity. Some of these are described in joined by melittin which in conjugation with PLA2 act upon RBCs, leucocytes, detail as following blood platlets and vascular endothelium. (A). PEPTIDES *Corresponding author. Ravi Kant Upadhyay (i) MELITTIN Melittin occurs in the bee venom is responsible for the major allergic reac- Department of Zoology, tions, which are alkaline in nature (Edstrom, 1992). Chemically, it is com- D D U Gorakhpur University, posed of 26 amino acids with amphipathic nature that allows it to interact Gorakhpur, India 273009 Journal of Pharmacy Research Vol.3.Issue 12. December 2010 3123-3128 Ravi Kant Upadhyay et al. / Journal of Pharmacy Research 2010, 3(12),3123-3128 with lipid membrane, which in turn facilitate its permeability to erythrocyte degranulation peptides (Hoffman, 1996) which causes massive release of his- and other cell membranes (Schmidt, 1982). Its tetrameric form causes a con- tamine (Gmachl, and Kreil, 1995; Hider and Dotimas, 1987) and binds to stant skin nerve depolarization and severe pain (Edstrom,1992) Melittin specific protein membrane receptors (Hider and Ragnarson, 1981). These are shows lytic effects on erythrocytes and damage intracellular membranes such rich in a-helix, and present two disulfide bonds in its structure (Dotimas et al., as lysosomes (Dotimas and Hider, 1987; Habermann, 1972) and release en- 1987) (Table 1). zymes (Henger and Habermann, 1972). Due to melittin action, leucocytes diameter is reduced, membrane disintegrated and increased matrix density. (B) ENZYMES Melittin induces the cardiotoxicity and causes transient increase in spontane- (i) PHOSPHOLIPASE A2 (PLA2) ous heart beat rate followed by decrease and cessation of heartbeat and do Phospholipase is highly active enzyme that exert more deleterious effects morphological
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