Comparative study on the ability of IgG and F(ab')2 antivenoms to neutralize lethal and myotoxic effects induced by Micrurus nigrocinctus (coral snake) venom.

Abstract

Abstract. A comparative study was performed on the ability of IgG and F(abЈ) 2 antivenoms to neutralize lethal and myotoxic activities of Micrurus nigrocinctus venom. Both antivenoms were adjusted to a similar neutralizing potency in experiments where venom and antivenoms were preincubated prior to injection. No significant differences were observed between IgG and F(abЈ) 2 antivenoms concerning neutralization of lethal effect in rescue experiments, i.e., when antivenom was administered intravenously after envenomation. However, F(abЈ) 2 antivenom was more effective in prolonging the time of death when subneutralizing doses were administered immediately after venom injection. Both products partially reversed the binding of M. nigrocinctus ␣-neurotoxins to acetylcholine receptor in vitro. The IgG and F(abЈ) 2 antivenoms effectively neutralized venom-induced myotoxicity when administered intravenously immediately after envenomation, although neutralization was poor if antivenom injections were delayed. Intramuscular injection of venom promoted diffusion of antivenom antibodies throughout muscle tissue, and F(abЈ) 2 diffused to a higher extent than IgG molecules. Thus, despite the observation that F(abЈ) 2 antivenom was more effective than IgG antivenom in prolonging the time of death when subneutralizing doses were administered immediately after envenomation, no major differences were observed in antivenom neutralization of lethal and myotoxic effects or in their capacity to reverse neurotoxin binding to the acetylcholine receptor.Antivenoms constitute the mainstay for treating snakebites 1 and many antivenoms are currently produced around the world. 2,3 The majority of these products are made of F(abЈ) 2 antibody fragments resulting from pepsin digestion of equine immunoglobulins, 4 although some manufacturers produce whole IgG antivenoms. 5 Pharmacokinetic studies show that F(abЈ) 2 fragments have a more convenient profile than whole IgG preparations since they have larger volumes of distribution and reach the tissue compartment at a faster rate. 6,7 Thus, it has been assumed that F(abЈ) 2 antivenoms are more effective than IgG products in reaching and neutralizing toxins within tissues. However, León and others 8 described that IgG and F(abЈ) 2 polyvalent antivenoms do not differ in their ability to neutralize local hemorrhage, edema, and myonecrosis induced by the venom of the crotaline snake Bothrops asper. It is therefore important to test this assumption in a variety of venom-antivenom systems.Coral snakes (genus Micrurus) are the representatives of the family Elapidae in America, 9 inflicting a number of accidents on this continent. [10][11][12] Although poorly studied, Micrurus venoms induce typical neurotoxic effects, with blockade of the neuromuscular synapse by ␣-neurotoxins that bind cholinergic receptors at the motor endplate. 13-15 Micrurus ␣-neurotoxins are similar to those of other elapids. 14,15 They are low molecular weight proteins that rapidly spread throughout tissues and bind acetylcholine r...

Role of hyaluronidase inhibitors in the neutralization of toxicity of Egyptian horned viper Cerastes cerastes venom

“…Although the available antivenom neutralizes the active venom components, stopping further damage but do not reverse the damage already done [26][27][28]52]. It is important to search for different venom inhibitors, either synthetic or natural, which would complement the action of antivenom, particularly in relation to the neutralization of local tissue damage.…”

Comparative assay of Vipera ammodytes antivenom potency

“…The antivenom was obtained as immunoglobulins concentrate by caprylic acid precipitation and dialisys method 8 , from sheep serum (Ovis aries, 2 years old males), previously hyperimmunized with Vipera ammodytes venom.…”

“…This kind of medicines is obtained from the hyperimmunized animals with one or more snake species venoms [4][5][6] . If the old antivenoms were separated and used as crude serum, the modern antivenoms embody mainly purified immunoglobulins concentrates 7,8 . Many factors affect the antivenom therapy, but the standardization and subsequently the methods to assess the product efficacy are very important.…”

“…The antivenom capability to annihilate certain toxic or biochemical venom properties grants the antivenom potency and can be expressed as median effective dose, ED 50 1,9 . One of the most used and aged antivenom potency assessing method is based on the injection in the animal experiment bodies of a significant venom-antivenom mixture and interpolation of the 50% survival animal 1,3,7,8,10,11 . Another way is represented by immunoenzymatic method for the assay of antivenom potency [11][12][13][14] .…”

Comparative abilities of IgG and F(ab)2 monovalent antivenoms to neutralize lethality, phospholipase A2, and coagulant activities induced by Daboia siamensis venom and their anticomplementary activity

“…These results support the notion that F(ab') 2 antivenoms are more effective than IgG antivenoms at neutralizing venom in tissue. However, some studies show that IgG and F(ab') 2 antivenoms do not differ in their abilities to neutralize the systemic and local effects of Bothrops asper venom [9][10][11][12][13][14] . It has been shown by in vitro methods that F(ab') 2 antivenoms have higher anticomplementary activity than IgG precipitated by caprylic acid and thus decreasing the risk of early adverse reactions occurring after antivenom treatment 14,15 .…”