Involvement of the AT1 Receptor in the Pathophysiology of the Respiratory Failure Induced by Scorpion Venom

Background: Renin-Angiotensin System (RAS) is related to cardiovascular diseases. It is also involved in the pathogenesis of pulmonary dysfunction, through the induction of proinflammatory mediators in lungs. Respiratory failure is a life-threatening complication in scorpion envenomation, a public health problem in Algeria. Our aim was to explore the role of angiotensin type I receptors (AT1R) in the respiratory dysfunction induced in an envenomed model with Androctonus australis hector (Aah) venom, in the presence or absence of an AT1R antagonist. Methods: Respiratory failure is assessed by the arterial blood gas analysis (pO2 and pCO2, sO2, hemoglobin and HCO3 concentration and pH), by neutrophil infiltration (myeloperoxidase activity) and oxidative stress markers (Nitrites, MDA, H2O2, catalase and GSH), in lungs and the pulmonary artery. Results: A severe respiratory dysfunction, including a marked perturbation of the oxygenation parameters and the acid base balance, reflecting a state of hypoxia and acidosis were induced by the venom. An important infiltration of neutrophils into the tissues and the generation of ROS with the alteration of the antioxidant system were found. Inhibition of the AT1R before envenomation revealed the recovery of the respiratory parameters in sera. The reduction of inflammatory cells infiltration and the prevention of the redox status imbalance were also recorded. Conclusion: These results indicate the involvement of Ang II throught the AT1R in the respiratory failure induced by Aah’s venom. However, further studies are still required to understand the RAS role in the pulmonary injury developed in the envenoming syndrome, a serious public health surgery that must be immediately treated

Effects of atropine and propranolol on lung inflammation in experimental envenomation: comparison of two buthidae venoms

Background Previous works had shown that scorpion venom induced neurotransmitter elevation and an inflammatory response associated with various anatomo-pathological modifications. The most dangerous scorpions species in Algeria responsible for these effects are Androctonus australis hector (Aah) and Androctonus amoreuxi (Aam). Results Comparison of the physiopathological effects induced by the two venoms showed differences in the kinetic of cytokine release and in lung injury. The lung edema was only observed in response to Aah venom and it was correlated with cell infiltration. In order to better understand the involved mechanism in inflammatory response, we used two antagonists, atropine (non-selective muscarinic antagonist) and propranolol (β adrenergic antagonist), which lead to a decrease of cell infiltration but has no effect on edema forming. Conclusion These results suggest another pathway in the development of lung injury following envenomation with Aam or Aah venom

Serotherapy against<em> </em>Voltage-Gated Sodium Channel-Targeting αToxins from <em>Androctonus</em> Scorpion Venom

Because of their venom lethality towards mammals, scorpions of the Androctonus genus are considered a critical threat to human health in North Africa. Several decades of exploration have led to a comprehensive inventory of their venom components at chemical, pharmacological, and immunological levels. Typically, these venoms contain selective and high affinity ligands for the voltage-gated sodium (Nav) and potassium (Kv) channels that dictate cellular excitability. In the well-studied Androctonus australis and Androctonus mauretanicus venoms, almost all the lethality in mammals is due to the so-called α-toxins. These peptides commonly delay the fast inactivation process of Nav channels, which leads to increased sodium entry and a subsequent cell membrane depolarization. Markedly, their neutralization by specific antisera has been shown to completely inhibit the venom’s lethal activity, because they are not only the most abundant venom peptide but also the most fatal. However, the structural and antigenic polymorphisms in the α-toxin family pose challenges to the design of efficient serotherapies. In this review, we discuss past and present accomplishments to improve serotherapy against Androctonus scorpion stings