Study of the design and analytical properties of the lethality neutralization assay used to estimate antivenom potency against Bothrops asper snake venom

Solano, Gabriela; Segura, Álvaro; Herrera, María; Gómez, Aarón; Villalta, Mauren; Gutiérrez, José Marı́a; León, Guillermo

doi:10.1016/j.biologicals.2010.05.006

Cited by 30 publications

(26 citation statements)

References 29 publications

Supporting

Mentioning

Contrasting

Unclassified

Order By: Relevance

“…Moreover, in some cases, the challenge dose is defined as the Minimum Lethal Dose (MLD) [37]. (b) The strain and weight of mice used in the tests, as some studies have revealed variations in the susceptibility of certain strains to venoms [38,39]. (c) The route of venom injection.…”

Section: Neutralization Of Lethality: the Gold Standard In The Prementioning

confidence: 99%

Preclinical Evaluation of the Efficacy of Antivenoms for Snakebite Envenoming: State-of-the-Art and Challenges Ahead

Gutiérrez

Solano

Plá

et al. 2017

Toxins

Self Cite

127

100

View full text Add to dashboard Cite

Animal-derived antivenoms constitute the mainstay in the therapy of snakebite envenoming. The efficacy of antivenoms to neutralize toxicity of medically-relevant snake venoms has to be demonstrated through meticulous preclinical testing before their introduction into the clinical setting. The gold standard in the preclinical assessment and quality control of antivenoms is the neutralization of venom-induced lethality. In addition, depending on the pathophysiological profile of snake venoms, the neutralization of other toxic activities has to be evaluated, such as hemorrhagic, myotoxic, edema-forming, dermonecrotic, in vitro coagulant, and defibrinogenating effects. There is a need to develop laboratory assays to evaluate neutralization of other relevant venom activities. The concept of the 3Rs (Replacement, Reduction, and Refinement) in Toxinology is of utmost importance, and some advances have been performed in their implementation. A significant leap forward in the study of the immunological reactivity of antivenoms against venoms has been the development of “antivenomics”, which brings the analytical power of mass spectrometry to the evaluation of antivenoms. International partnerships are required to assess the preclinical efficacy of antivenoms against snake venoms in different regions of the world in order to have a detailed knowledge on the neutralizing profile of these immunotherapeutics.

show abstract

Section: Neutralization Of Lethality: the Gold Standard In The Prementioning

confidence: 99%

Preclinical Evaluation of the Efficacy of Antivenoms for Snakebite Envenoming: State-of-the-Art and Challenges Ahead

Gutiérrez

Solano

Plá

et al. 2017

Toxins

Self Cite

127

100

View full text Add to dashboard Cite

show abstract

“…The LD 50 value is defined as the amount of a substance (or venom) causing death of 50% injected mice [4,7,8,9,10,11,12,13]. …”

Section: Introductionmentioning

confidence: 99%

Evaluation of the Lethal Potency of Scorpion and Snake Venoms and Comparison between Intraperitoneal and Intravenous Injection Routes

Oukkache

Jaoudi²,

Ghalim

et al. 2014

Toxins

View full text Add to dashboard Cite

Scorpion stings and snake bites are major health hazards that lead to suffering of victims and high mortality. Thousands of injuries associated with such stings and bites of venomous animals occur every year worldwide. In North Africa, more than 100,000 scorpion stings and snake bites are reported annually. An appropriate determination of the 50% lethal doses (LD50) of scorpion and snake venoms appears to be an important step to assess (and compare) venom toxic activity. Such LD50 values are also commonly used to evaluate the neutralizing capacity of specific anti-venom batches. In the present work, we determined experimentally the LD50 values of reference scorpion and snake venoms in Swiss mice, and evaluated the influence of two main venom injection routes (i.e., intraperitoneal (IP) versus intravenous (IV)). The analysis of experimental LD50 values obtained with three collected scorpion venoms indicates that Androctonus mauretanicus (Am) is intrinsically more toxic than Androctonus australis hector (Aah) species, whereas the latter is more toxic than Buthus occitanus (Bo). Similar analysis of three representative snake venoms of the Viperidae family shows that Cerastes cerastes (Cc) is more toxic than either Bitis arietans (Ba) or Macrovipera lebetina (Ml) species. Interestingly, the venom of Elapidae cobra snake Naja haje (Nh) is far more toxic than viper venoms Cc, Ml and Ba, in agreement with the known severity of cobra-related envenomation. Also, our data showed that viper venoms are about three-times less toxic when injected IP as compared to IV, distinct from cobra venom Nh which exhibited a similar toxicity when injected IP or IV. Overall, this study clearly highlights the usefulness of procedure standardization, especially regarding the administration route, for evaluating the relative toxicity of individual animal venoms. It also evidenced a marked difference in lethal activity between venoms of cobra and vipers, which, apart from the nature of toxins, might be attributed to the rich composition of high molecular weight enzymes in the case of viper venoms.

show abstract

“…The challenge doses employed were: two LD 50 for lethality; two E. ocellatus venom MCCs for coagulation; 2 mg of N. nigricollis venom for PLA 2 activity; and 20 mg (0.16 mg/mL) and 10 mg (0.08 mg/mL) of E. ocellatus and B. arietans venoms, respectively, for proteolytic activity. The neutralizing ability of antivenoms for lethal, PLA 2 and proteolytic activities was expressed as Median Effective Dose (ED 50 ), corresponding to the ratio of mg venom/mL antivenom in which the activity of the control venom was reduced by 50% [31,32]. In the case of the coagulant effect, neutralization was expressed as Effective Dose (ED), i.e.…”

Section: Neutralization Of Toxic and Enzymatic Activities By Antivenomsmentioning

confidence: 99%

Purification of equine whole IgG snake antivenom by using an aqueous two phase system as a primary purification step

et al. 2015

Self Cite

View full text Add to dashboard Cite

Study of the design and analytical properties of the lethality neutralization assay used to estimate antivenom potency against Bothrops asper snake venom

Cited by 30 publications

References 29 publications

Preclinical Evaluation of the Efficacy of Antivenoms for Snakebite Envenoming: State-of-the-Art and Challenges Ahead

Preclinical Evaluation of the Efficacy of Antivenoms for Snakebite Envenoming: State-of-the-Art and Challenges Ahead

Evaluation of the Lethal Potency of Scorpion and Snake Venoms and Comparison between Intraperitoneal and Intravenous Injection Routes

Purification of equine whole IgG snake antivenom by using an aqueous two phase system as a primary purification step

Contact Info

Product

Resources

About