RESUMEN
OBJECTIVES: To investigate the antiinflammatory activity of Serenoa repens (SeR), LY, and) on proinflammatory phenotype in rat peritoneal macrophages (Ms) stimulated with Salmonella enteritidis lipopolysaccharide (LPS) and in the prostate of rats with partial bladder outlet obstruction. SeR, combined with other compounds, such as LY and Se is used to relieve symptoms associated with benign prostatic hyperplasia (BPH). Inflammation plays a pivotal role in the pathogenesis of BPH and represents a target for anti-BPH drugs. METHODS: After stimulation with 1 µg/mL of LPS, peritoneal rat MΦs were coincubated with LY (2 µg/mL), Se (0.03 µg/mL), and SeR (10 µg/mL), alone or in association (LY-Se-SeR) and with RPMI. Inducible cyclooxygenase (COX-2), 5-lypoxygenase (5-LOX), inducible nitric oxide synthase (iNOS), and inhibitor κBα (IκB-α) protein were evaluated by Western blot. Nuclear factor-kappa B (NF-κB) binding activity was measured by electrophoretic mobility shift assay. Tumor necrosis factor-α (TNF-α) gene expression was investigated by real-time polymerase chain reaction. We also evaluated malondialdehyde (MDA) and nitrite levels. RESULTS: LPS stimulation produced a proinflammatory phenotype in rat peritoneal MΦs. LY, Se, and SeR inhibited the inflammatory cascade, but the Ly-Se-SeR association caused a greater inhibitory effect on the expression of COX-2, 5-LOX, and iNOS. The Ly-Se-SeR association showed a higher efficacy in reducing the loss of IκB-α, the increased NF-κB binding activity, the enhanced mRNA levels of TNF-α, the elevated MDA, and nitrite content. The LY-Se-SeR association in vivo caused a greater inhibitory effect on prostate inflammation induced in rats by partial bladder outlet obstruction. CONCLUSIONS: The LY-Se-SeR association might be useful in the treatment of BPH.
Asunto(s)
Antioxidantes/farmacología , Carotenoides/farmacología , Proteínas I-kappa B/efectos de los fármacos , Proteínas I-kappa B/genética , Macrófagos Peritoneales/efectos de los fármacos , Selenio/farmacología , Serenoa , Animales , Células Cultivadas , Inflamación/inmunología , Licopeno , Masculino , Inhibidor NF-kappaB alfa , Fenotipo , Próstata/efectos de los fármacos , Próstata/inmunología , Ratas , Ratas Sprague-Dawley , Obstrucción del Cuello de la Vejiga Urinaria/inmunologíaRESUMEN
In rat experimental varicocele, polydeoxyribonucleotide (PDRN) induces vascular endothelial growth factor (VEGF) production, thereby enhancing testicular function. This may point to a new therapeutic approach in human varicocele.
Asunto(s)
Polidesoxirribonucleótidos/farmacología , Polidesoxirribonucleótidos/uso terapéutico , Receptor de Adenosina A2A/metabolismo , Regulación hacia Arriba/fisiología , Varicocele/metabolismo , Varicocele/prevención & control , Factor A de Crecimiento Endotelial Vascular/biosíntesis , Animales , Masculino , Sustancias Protectoras/farmacología , Sustancias Protectoras/uso terapéutico , Distribución Aleatoria , Ratas , Ratas Sprague-Dawley , Testículo/patología , Varicocele/patologíaRESUMEN
BACKGROUND: The aim of our study was to determine whether intermittent hemodiafiltration (HDF) leads to an alteration in monocyte antiviral activity as well as in the in vitro release of cytokines such as interleukin-12 (IL-12), tumor necrosis factor-alpha (TNF-alpha) and interferon-alpha (IFN-alpha) by the same cells. METHODS: We enrolled 25 patients undergoing HDF for 3.5-4 hours 3 times a week (12 men, 13 women; mean age 58 +/- 6.7 years) and 25 healthy donors (ND) (12 men, 13 women; mean age 57 +/- 8 years). Monocytes from peripheral blood mononuclear cells were isolated with a Monocyte Isolation Kit II. Monocytic cells were infected with herpes simplex virus type 2 (HSV-2). Cytokines were assayed in supernatants. RESULTS: The in vitro antiviral activity of monocytes from HDF patients was significantly impaired with respect to ND. Furthermore, monocytes from post-HDF patients were more prone to viral infection. Lipopolysaccharide (LPS) stimulation induced significant viral inhibition only in monocytes from NDs (p<0.05). The cytokine pattern (TNF-alpha, IFN-alpha and IL-12) in monocytes stimulated with LPS was markedly inhibited in HDF patients compared with ND (p<0.05). A basal production of TNF-alpha was found in monocytes from pre-HDF and post-HDF patients. No IFN-alpha production was found in LPS-stimulated and HSV-2-infected monocytes from pre-HDF and post-HDF patients. IL-12 production appeared significantly decreased after HDF in all experimental conditions (p<0.05). CONCLUSIONS: The significant increase of viral replication in monocytes from HDF patients compared with healthy donors could be related to a significant reduction of cytokine production. Moreover, the dialytic session influenced the intrinsic antiviral activity of monocytes, favoring viral replication.