Renal Effects of Supernatant from Macrophages Activated by Crotalus durissus cascavella Venom: The Role of Phospholipase A2 and Cyclooxygenase

Health Science Center, University of Fortaleza-UNIFOR, Fortaleza, Ceara, Brazil.
Pharmacology &amp Toxicology 02/2003; 92(1):14-20. DOI: 10.1034/j.1600-0773.2003.920103.x
Source: PubMed


In Brazil, the genus Crotalus is responsible for approximately 1500 cases of snakebite annually. The most common complication in the lethal cases is acute renal failure, although the mechanisms of the damaging effects are not totally understood. In this work, we have examined the renal effects caused by a supernatant of macrophages stimulated by Crotalus durissus cascavella venom as well the potential role of phospholipase A2 and cyclo-oxygenase. Rat peritoneal macrophages were collected and placed in a RPMI medium and stimulated by crude Crotalus durissus cascavella venom (1, 3 or 10 microg/ml) for 1 hr. They were then washed and kept in a culture for 2 hr. The supernatant (1 ml) was tested in an isolated perfused rat kidney. The first 30 min. of each experiment were used as an internal control, and the supernatant was added to the system after this period. All experiments lasted 120 min. A study of toxic effect on perfusion pressure, glomerular filtration rate, urinary flow percent of sodium tubular transport and percent of proximal tubular sodium transport was made. The lowest concentration of venom (1 microg/ml) was not statistically different from the control values. The most intense effects were seen at 10 microg/ml for all renal parameters. The infusion of the supernatant of macrophages stimulated with crude venom (3 or 10 microg/ml) increased the perfusion pressure, glomerular filtration rate and urinary flow, decreased the percent of sodium tubular transport and percent of proximal tubular sodium transport. Dexamethasone (10 microM) and quinacrine (10 microM) provided protection against the effect of the venom on glomerular filtration rate, urinary flow, percent of sodium tubular transport, percent of proximal tubular sodium transport and perfusion pressure. Indomethacin (10 microM) and nordiidroguaretic acid (1 microM) reversed almost all functional changes, except those of the perfusion pressure. These results suggest that macrophages stimulated with Crotalus durissus cascavella venom release mediators capable of promoting nephrotoxicity in vitro. Moreover, phospholipase A2 and cyclooxygenase products are involved in these biologic effects.

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    • "Acute renal failure is a frequent complication observed in victims of snakebites. Evaluation of renal function parameters after crude venom administration has suggested a direct effect on glomerular filtration rate, a slow and steady accumulation of nitrogenous waste products, and an inability of the kidney to regulate the balance of sodium, electrolytes, acid, and water [10] [11] [12] [13]. Girón et al. [14] demonstrated that the intravenous and intraperitoneal "
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    ABSTRACT: In this study, we investigated in groups of female BALB/c mice injected with Crotalus durissus terrificus venom (Cdt) the renal function based on creatinine clearance, percentage of fractional excretion cytokines and histological examination of renal tissue. Cdt caused renal alterations that induced proteinuria during the initial hours post-venom and reduced creatinine clearance 15 min. up to 2 hours post-venom administration. In urine from mice injected with Cdt induced a decrease in IL-4 levels. More pronounced increments of IL-5, IL-6 and IFN-γ were observed after 15 and 30 min, respectively. The highest levels of TNF and IL-10 were observed at 1 and 4 hs, respectively. The ratios of pro- and anti-inflammatory cytokines in animals injected with Cdt, which may be manifested in the inflammatory status during the envenoming. In groups of animals treated with Cdt were observed a decreasing in creatinine clearance and its effect on glomerular filtration rate was accompanied by decreased fractional excretion of cytokines and morphologic disturbances. This loss of change selectively in envenomation could thus explain why the relatively excretion of cytokines is reduced while of total proteins increases. In conclusion the fractional excretion of cytokines is significantly reduced in mice injected with Cdt, despite proteinuria.
    Mediators of Inflammation 11/2011; 2011:103193. DOI:10.1155/2011/103193 · 3.24 Impact Factor
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    • "A.G.C. Bonavita et al. / Toxicon 47 (2006) 885–893 889 stimuli have been identified (Julius and Basbaum, 2001), suggesting that distinct chemical modulation may be implicated in thermal and mechanical hyperalgesia systems. Venom toxins were reported for their property of activating some constitutive as well as inflammatory cells (Cardoso et al., 2001; Farsky et al., 2000; Landucci et al., 1998; Martins et al., 2003; Schweitz et al., 1989). We demonstrated herein that Bjv induced a dose-and timedependent degranulation of mast cells, a phenomenon shown to be sensitive to treatment with stabilizers sodium cromoglicate and sodium nedocromil. "
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    ABSTRACT: Bothrops jararaca venom (Bjv) is known to induce local inflammation and severe pain. Since, mast cells are able to secrete mediators involved in algesic processes, in this study we examined the putative role of these cells in the hyperalgesia triggered by Bjv in the rat paw. We noted that treatment with mast cell stabilizer sodium cromoglicate as well as with histamine and 5-hydroxytriptamine receptor antagonists meclizine and methysergide, respectively, inhibited the Bjv-induced hyperalgesia. In addition, we showed that stimulation of isolated rat peritoneal mast cells with Bjv in vitro resulted in the release of stored and neo-generated inflammatory mediators such as histamine and leukotriene C(4), respectively. Bjv-induced histamine secretion was clearly sensitive to treatment with sodium cromoglicate and sodium nedocromil. We further observed that metalloproteinase inhibitors 1,10-phenantroline and DM43 inhibited mast cell degranulation in vitro, under conditions where inhibitors of phospholipase A(2) as well as of serine- and cysteine-proteinases were inactive. Altogether, our findings indicate that mast cells seem to contribute to the hyperalgesia caused by Bjv in the rat paw, and also provide evidence that this response might be dependent on the ability of the Bjv to activate directly mast cells.
    Toxicon 07/2006; 47(8):885-93. DOI:10.1016/j.toxicon.2006.02.017 · 2.49 Impact Factor
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