Abstract
BackgroundSnake venoms contain various bioactive constituents which possess potential therapeutic effects. The aim of this work was to investigate the effect of the extract from Agkistrodon halys venom on lipopolysaccharide (LPS)-induced myocardial injury.MethodsThirty male Sprague-Dawley rats were randomly assigned to three groups (10 rats per group): control group, LPS group and LPS + extract group. Rats in control and the LPS groups were intravenously injected with sterile saline solution, and rats in the LPS + extract group with the extract. After 2 h, rats of the control group were intraperitoneally injected sterile saline solution, and rats in the LPS and the LPS + extract groups were treated with LPS (20 mg per kg body weight). Levels of creatine kinase (CK) and lactate dehydrogenase (LDH) in serum were determined. Anti-inflammation of the extract was analyzed via determination of TNF-α and IL-6 in serum, and expression of TNF-α, IL-6, COX-2 and p-ERK protein in hearts. Heme oxygenase-1 (HO-1) and p-NF-κB protein expression in hearts, superoxide dismutase (SOD) activity and malondialdehyde (MDA) level in serum were used to evaluate the anti-oxidative properties of the extract.ResultsExtract pretreatment significantly decreased the level of serum CK and LDH, reduced the generation of inflammatory cytokines such as TNF-α and IL-6, and also reduced serum level of MDA in the LPS + extract group compared with the LPS group. In addition, the extract increased SOD activity in serum, HO-1 protein expression in hearts, and decreased TNF-α, IL-6, COX-2, p-NF-κB and p-ERK1/2 protein expression.ConclusionOur results suggested that beneficial effect of this extract might be associated with an improved anti-oxidation and anti-inflammatory effect via downregulation of NF-κB/COX-2 signaling by activating HO-1/CO in hearts.
Highlights
Snake venoms contain various bioactive constituents which possess potential therapeutic effects
Activated PC (APC) increases the survival of patients with sepsis through its antiinflammatory effect [25] by reducing both nuclear factorκB (NF-κB) pathway and expression of pro-inflammatory cytokines such as tumor necrosis factor-α (TNF-α) and IL-6 induced by LPS [26, 27]
Effect of the extract on creatine kinase (CK) and lactate dehydrogenase (LDH) The extract used in the study was a component which we recently isolated from Agkistrodon halys venom
Summary
Snake venoms contain various bioactive constituents which possess potential therapeutic effects. The aim of this work was to investigate the effect of the extract from Agkistrodon halys venom on lipopolysaccharide (LPS)-induced myocardial injury. Many progresses have been made in the use of snake venom constituents to develop medications including anti-hypertensive and anti-stroke drugs, and some studies suggested that venom extracts possess anti-cancer activity [21, 22]. APC increases the survival of patients with sepsis through its antiinflammatory effect [25] by reducing both NF-κB pathway and expression of pro-inflammatory cytokines such as TNF-α and IL-6 induced by LPS [26, 27]. We hypothesize that PCA from snake venom attenuates LPS-induced myocardial injury on the basis of previous results. In the present work the effect of the extract on myocardial injury in sepsis induced by LPS was further analyzed, together with its anti-inflammatory and antioxidative effects
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