Pharmaco-Modulations of Induced Edema and Vascular Permeability Changes by Vipera lebetina Venom: Inflammatory Mechanism
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Pharmaco-Modulations of Induced Edema and Vascular Permeability Changes by Vipera lebetina Venom: Inflammatory Mechanisms Fatima Sebia-Amrane1,2 and Fatima Laraba-Djebari1,2,3
Abstract—The inflammatory response induced by Vipera lebetina venom (VLV) in the mice hind paw was evaluated by paw edema value and vascular permeability changes. The edema was produced in a dose- and time-dependent manner. This response was maximal within 2 h and disappeared after 24 h The minimum edema-forming dose was estimated at 0.8 μg/20 g body weight. Microscopic examination confirmed that VLV also induces skin structure alterations with collagen fiber dissociation and polynuclear infiltration, which is characteristic of edema formation. The induced edema with VLV (1 μg/paw) could be due to the release of pharmacological active substances at the site of injection. Histamine, serotonine, and arachidonate metabolites may play important roles in the vasoactive and edematic effect of VLV since pretreatment of mice with cromoglycate, cyproheptadine, ibuprofen, loratidine, and indomethacin significantly reduced the edema formation (77, 63, 57, 45, and 43 %, respectively). The obtained results demonstrate that the induced edema and vasodilatation by this venom may be triggered and maintained by different pharmacological mechanisms, since cromoglycate and cyproheptadine were the most active inhibitors of the edema. The relationships between histamine and serotonin release from mast cells and arachidonate metabolites activation could be the main step in edema-forming and the induced vasodilatation by the venom. KEY WORDS: VLV; edema; vascular permeability; inflammation.
INTRODUCTION
venom components (PLA2, proteases, and bioamines) play a relevant role in the inflammatory response, contributing to edema-forming and tissue damage [3]. Reactions of a local type may involve an intense sharp pain, swelling, and severe itching. Local alterations are the consequences of an increase in vascular permeability and leukocyte influx [4]. Viperidae venoms contain diverse enzymatic activities, which suggest that concurrent pathogenic mechanisms are active. Various categories of chemically different molecules isolated from VLV induce inflammatory reactions and have been claimed to contribute to the severity of local symptoms present in this envenomation. Siigur and collaborators [5] showed that VLV contains bradykininreleasing enzyme. They also reported the isolation of lebetase, a fibrinolytic metalloproteinase of molecular weight 23.7 kDa. The enzyme is directly acting, degrading the fibrin and fibrinogen chain somewhat
Snakes from Viperidae family are responsible for the majority of snakebites in the world. The effects induced by venoms obtained from Viperidae specimens have been studied clinically and experimentally and include a complex series of local and systemic alterations such as local myonecrosis, hemorrhage, and edema, as well as systemic hemorrhage and acute renal failure. Local edema is often the prominent early feature caused by venom at the bite site [1,
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