Involvement of Kallikrein-Kinin System on Cardiopulmonary Alterations and Inflammatory Response Induced by Purified Aah
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Involvement of Kallikrein-Kinin System on Cardiopulmonary Alterations and Inflammatory Response Induced by Purified Aah I Toxin from Scorpion Venom Wafa Medjadba,1 Marie-France Martin-Eauclaire,2 and Fatima Laraba-Djebari1,3
Abstract—Bradykinins are released from kininogen by kallikrein. They increase capillary lung permeability after their binding to β1 and especially β2 receptors before being metabolized by kininase enzyme. This study was performed to evaluate cardiopulmonary damages and inflammatory response on injected rats with Aah I toxin of scorpion venom and the involvement of Kallikrein-Kinin system in this pathogenesis. Obtained results revealed that Aah I toxin induces inflammatory cell infiltration accompanied by cellular peroxidase activities, a release of cytokine levels, pulmonary and myocardial damage, with altered metabolic activities and imbalanced redox status. Administration of aprotinin (bradykinin inhibitor) and especially icatibant (bradykinin β2 receptor antagonist) seemed to be able to protect animals against the toxicity of Aah I; nevertheless, the use of captopril (kininase II inhibitor) reduced partially some cardiac disorders. These findings indicate that the kallikrein-kinin system may contribute to the physiopathological effect and lung edema formation induced by toxin, which suggests a potential use of drugs with significant anti-kinin properties. KEY WORDS: kallikrein-kinin system; lung permeability; inflammation; Aah I neurotoxin; cardiopulmonary damage.
INTRODUCTION Scorpion stings represent a medical problem in many countries, and envenomation symptoms are associated with pulmonary edema (PE) and myocardial injury in the most severe cases [1]. These symptoms have been attributed to the neurotoxins’ pharmacological effects [2, 3]. Androctonus australis hector, the most dangerous scorpion
1
USTHB, Faculty of Biological Sciences, Laboratory Cellular and Molecular Biology, Department Cellular and Molecular Biology, BP32, EL Alia, Bab Ezzouar, 16111 Algiers, Algeria 2 Aix-Marseille University, CNRS UMR 7286 CRN2M, IFR Jean-Roche, Faculté de Médecine Nord, Bd Pierre Dramard, 13916 Marseille, Cedex 20, France 3 To whom correspondence should be addressed at USTHB, Faculty of Biological Sciences, Laboratory Cellular and Molecular Biology, Department Cellular and Molecular Biology, BP32, EL Alia, Bab Ezzouar, 16111 Algiers, Algeria. E-mail: [email protected]; [email protected] Abbreviations: Aah, Androctonus australis hector; Aah I, Neurotoxins purified from Aah venom; ACE, Angiotensin-converting enzyme; ACEI, Angiotensin-converting enzyme inhibitor; Apro, Aprotinine; Cap, Captopril; Icati, lcatibant; IL-1β, Cytokines: Interleukin-1β; IL-6, Interleukin-6; I-10, Interleukin-10; MDA, Malondialdehyde
species in Algeria, contains three alpha toxins (Aah I to III), which are responsible for the majority of the toxicity in mammals [4]. Previous studies reported that edema formation in the lung can be attributed to acute left ventricular failure [5, 6]. However, other authors attribute thes
