Elsevier

Toxicon

Volume 127, 1 March 2017, Pages 77-84
Toxicon

Role of some vasoactive mediators in scorpion envenomed children: Possible relation to envenoming outcome

https://doi.org/10.1016/j.toxicon.2017.01.006Get rights and content

Highlights

  • Disturbances of vasoactive mediators, hormonal and electrolyte imbalance were obvious in scorpion envenomed children.

  • The complication was obvious in children below 5 years old.

  • The magnitude of elevation/decline of these biomarkers was directly related to the occurrence of complication.

  • Profiling these biomarkers could be considered for evaluation in scorpion envenomed children.

  • The use of inhibitors of these vasoactive biomarkers should be considered as a line of treatment.

Abstract

Scorpion envenomation causes an autonomic storm resulting in changes in the vasoactive mediators’ levels which lead to myocardial damage, cardiovascular disturbances, peripheral circulatory failure, pulmonary edema, multi-system-organ-failure and death. The study aimed to determine the circulating levels of adrenaline, noradrenaline, angiotensin converting enzyme (ACE), Angiotensin II (Ang II), kallikrein enzyme, nitric oxide (NO), aldosterone, and electrolytes Na+, K+ and Ca+2 in scorpion envenomed children and to evaluate the potential relation between these vasoactive mediators, the severity of scorpion envenoming and the clinical outcome of envenomed children. Forty envenomed children (22 mild and 18 severe cases) along with 10 healthy control children were enrolled in the study. The circulating levels of adrenaline, noradrenaline, Ang II, ACE, kallikrein enzyme, and NO were determined by ELISA, and spectrophotometric assays on admission and 24 h later. On admission, serum aldosterone, and electrolytes; Na+, K+ and Ca+2 were determined by RIA, Flame photometer and Flame atomic absorption respectively. All envenomed children showed significant surge of adrenaline, noradrenaline, ACE, Ang II, aldosterone, NO and Na+, that concomitantly faced by significant reduction in kallikrein, K+ and Ca+2 on admission. Twenty four hours later, all envenomed children continued to show significant elevation of ACE, Ang II and NO. The severely envenomed children showed considerable reduction in circulating levels of adrenaline, noradrenaline, ACE and Ang II, while dramatic increase in kallikrein activity was reported in comparison to mildly envenomed children after 24 h of medical care. Also, NO exhibited considerable accumulation in non survivors, on admission, that was persistent for the subsequent 24 h and was accompanied by high kallikrein, low catecholamines and Ang II levels compared to survivors. Finally, the hypertensive cases showed substantial higher levels of catecholamine, ACE and Ang II, 24 h after admission. These findings indicated that, disturbances of the studied vasoactive mediators were common in scorpion envenomed children and may account for several inflammatory manifestations and clinical outcome. ACE inhibitors could be considered as possible therapeutic agent in victims with prominent increase in ACE and Ang II while kallikrein inhibitor and antioxidants may be effective in the treatment of late hypotensive ones.

Introduction

Scorpion envenomation is a common health problem in many tropical and subtropical countries, and is an important cause of morbidity and mortality, especially among children (Dehghankhalili et al., 2015, Fukuhara et al., 2004). In Upper Egypt, particularly, Assiut Governorate, scorpion envenomation still represents a medical problem and a life hazard (Mohamad et al., 2014, Mohey-Eldeen and Meki, 1996). Single venom may contain hundreds of different components producing diverse pathological effects. Scorpion venom contains muco-polysaccharides, hyaluronidase, phospholipase, serotonin, histamine, and neurotoxins. Neurotoxins are the most important components of the venom. These low-molecular weight polypeptides cause severe adrenergic and cholinergic activities and adversely affect sodium, potassium, and chloride channels of various cells (Bawaskar and Bawaskar, 2003, Utkin, 2015).

Severe scorpion envenoming causes an autonomic storm resulting in massive release of catecholamines, angiotensin converting enzyme (ACE), angiotensin II (Ang II), glucagon, cortisol, bradykinin, prostaglandins and changes in insulin secretion. All these agents cause stimulation of neuro-endocrinal-immunological axis and are proved to induce the release of immunological mediators as IL-6, and RANTES (Abdel-Haleem et al., 2006). As a consequence of these changes in the hormonal milieu, scorpion envenoming results in a syndrome of fuel energy deficits and inability of the vital organs to utilize the existing metabolic substrates, which causes myocardial damage, cardiovascular disturbances, peripheral circulatory failure, pulmonary edema, and many other clinical manifestations alone or in combination, producing multi-system organ failure and death (Chippaux, 2012, Murthy, 2000). The clinical manifestations are characterized by transient cholinergic (vomiting, sweating, bradycardia, ventricular premature contraction, salivation and hypotension) and prolonged sympathetic stimulation (hypertension, tachycardia, pulmonary edema and shock (Bawaskar and Bawaskar, 2003).

Nitric oxide (NO) plays a critical role in the regulation of vascular tone, organ blood flow as well as inhibition of platelets and neutrophils aggregation. However, excessive production of NO has been reported in several myocardial disorders involving inflammatory process such as endotoxic shock and heart failure (Lecour et al., 2001). Systemic inflammatory response that is associated with NO overproduction may contribute to vascular hyporeactivity, hypotension and organ failure in scorpion envenomation (Sahan-Firat et al., 2012).

The aim of the present study was to determine circulating levels of adrenaline, noradrenaline, ACE, Ang II, kallikrein enzyme, NO, aldosterone and electrolytes including Na+, K+ and Ca+2 in scorpion envenomed children on and 24 h after admission. Also, the study was set to evaluate the potential relation between these vasoactive mediators and the severity and outcome of scorpion envenoming in children.

Section snippets

Patients and methods

This study was carried out at Pediatrics and Biochemistry Departments, Assiut University, during the summer (May, June and July) of 2015. Written informed consents were taken from the parents of participating children. The study was approved by the ethics committee of Faculty of Medicine, Assiut University, Assiut, Egypt.

Results

The present study included 40 scorpion envenomed children with mean age 6.5 ± 0.7 years and 10 apparently healthy controls. Twenty two and eighteen patients were mildly and severely envenomed respectively. The severe cases were classified into 12 survival and 6 non-survival cases. According to blood pressure measurements, the study included 13 hypertensive and 9 hypotensive cases on admission but after 24 h, the study include 12 hypotensive and 6 hypertensive cases. In addition, the study

Discussion

Scorpion envenomation in children is a potentially fatal condition caused by neurotoxins and cardiotoxins that present in the majority of scorpion venoms (Meki and Mohey El-Dean, 1998, Mohamad et al., 2014). Massive release of catecholamines, Ang II, ACE, glucagon, cortisol, and changes in insulin secretion results in a syndrome of fuel energy deficits with subsequent multi-system-organ-failure and death (Konca et al., 2015, Murthy, 2000). Moreover, Viswanathan and Prabhu (2011) and Berger

Funding

This research did not receive any specific grant from funding agencies in the public, commercial, ornot-for-profit sectors.

Conflicts of interest

The Authors declare no conflict of interest

Ethical statement

This study was carried out at Pediatric and Biochemistry Departments, Assiut University, during the summer months (May, June and July) of 2015. Written informed consent was taken from the parents of children participants and this study was approved from the ethics committee of Faculty of Medicine, Assiut University, Assiut, Egypt.

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