ABSTRACT
Phospholipases A2 (PLA2s) from snake venom possess antitumor and antiangiogenic properties. In this study, we evaluated the antimetastatic and antiangiogenic effects of MjTX-II, a Lys49 PLA2 isolated from Bothrops moojeni venom, on lung cancer and endothelial cells. Using in vitro and ex vivo approaches, we demonstrated that MjTX-II reduced cell proliferation and inhibited fundamental processes for lung cancer cells (A549) growth and metastasis, such as adhesion, migration, invasion, and actin cytoskeleton decrease, without significantly interfering with non-tumorigenic lung cells (BEAS-2B). Furthermore, MjTX-II caused cell cycle alterations, increased reactive oxygen species production, modulated the expression of pro- and antiangiogenic genes, and decreased vascular endothelial growth factor (VEGF) expression in HUVECs. Finally, MjTX-II inhibited ex vivo angiogenesis processes in an aortic ring model. Therefore, we conclude that MjTX-II exhibits antimetastatic and antiangiogenic effects in vitro and ex vivo and represents a molecule that hold promise as a pharmacological model for antitumor therapy.
Subject(s)
Angiogenesis Inhibitors , Bothrops , Cell Proliferation , Crotalid Venoms , Lung Neoplasms , Animals , Humans , Angiogenesis Inhibitors/pharmacology , Lung Neoplasms/drug therapy , Cell Proliferation/drug effects , Phospholipases A2/pharmacology , Cell Movement/drug effects , Human Umbilical Vein Endothelial Cells/drug effects , Vascular Endothelial Growth Factor A/metabolism , A549 Cells , Cell Line, Tumor , Antineoplastic Agents/pharmacology , Neovascularization, Pathologic/drug therapy , Reactive Oxygen Species/metabolism , Venomous SnakesABSTRACT
Objective: This study aimed to evaluate the effects of ovariectomy on glycerol-induced renal changes in rats. Methods: Twenty-four female Wistar rats were submitted to ovariectomized (OVX) or sham surgery. One week after surgery, the animals received an intramuscular injection (8ml/kg) of 50% glycerol or saline (0.15 M) solution. These animals were divided into the following groups (n=6 per group): Sham, sham-operated female rats injected with saline; OVX, ovariectomized female rats injected with saline; Sham+Gly, sham-operated female rats injected with glycerol; OVX+Gly, ovariectomized female rats injected with glycerol. All rats were euthanized 3 days after the injections and the kidneys were removed for histological and immunohistochemical studies. Blood and urine samples were also collected for renal function studies. Results: The OVX+Gly group presented higher creatinine serum levels, as well as greater fractional excretion of sodium and urinary flow than the Sham+Gly group. Histological lesions and tubulointerstitial staining for macrophages, nuclear factor-kappa B, and nitrotyrosine were more pronounced in the renal cortex of the OVX+Gly group compared to the Sham+Gly group. Conclusion: We conclude that ovariectomy aggravated changes in renal function and structure in glycerol-induced acute kidney injury by the intensification of the proinflammatory tissue response.
Objetivo: Avaliar os efeitos da ovariectomia nas alterações renais induzidas pelo glicerol em ratas. Métodos: Vinte e quatro ratas Wistar foram submetidas à ovariectomia (OVX) ou cirurgia sham (intervenção falsa). Uma semana após a cirurgia, os animais receberam injeção intramuscular (8ml/kg) de glicerol a 50% ou solução salina (0,15 M). As ratas foram divididas nos seguintes grupos (n=6 por grupo): Sham, fêmeas sham-operadas e injetadas com solução salina; OVX, fêmeas ovariectomizadas e injetadas com solução salina; Sham+Gly, fêmeas sham-operadas e injetados com glicerol; OVX+Gly, fêmeas ovariectomizadas e injetadas com glicerol. Todas as ratas foram eutanasiadas 3 dias após as injeções e os rins foram removidos para estudos histológicos e imuno-histoquímicos. Amostras de sangue e urina também foram coletadas para estudos de função renal. Resultados: O grupo OVX+Gly apresentou maiores níveis séricos de creatinina, assim como maiores fração de excreção de sódio e fluxo urinário do que o grupo Sham+Gly. As lesões histológicas e imunomarcação tubulointersticial para macrófagos, fator nuclear-kappa B e nitrotirosina foram mais pronunciadas no córtex renal do grupo OVX+Gly em comparação ao grupo Sham+Gly. Conclusão: Concluímos que a ovariectomia agravou as alterações na função e estrutura renal, na lesão renal aguda induzida por glicerol, pela intensificação da resposta tecidual pró-inflamatória.
