Protective effect of nebivolol on rat ovary exposed to deltamethrin toxicity

Purpose: We aimed to investigate the antioxidant activity of nebivolol against possible damage to the ovarian tissue due to the application of deltamethrin as a toxic agent, by evaluating histopathological proliferating cell nuclear antigen (PCNA) and tumor necrosis factor-alpha (TNF-α) signal molecules immunohistochemically. Methods: The animals were divided into three groups as control, deltamethrin and deltamethrin + nebivolol groups. Vaginal smears were taken after the animals were mated and detected on the first day of pregnancy. After the sixth day, deltamethrin (0.5 mL of 30 mg/kg BW undiluted ULV), and 2 mL of sterile nebivolol solution were administered intraperitoneally every day for 6-21 periods. After routine histopathological follow-up, the ovarian tissue was stained with hematoxylin and eosin stain. Results: Control group showed normal histology of ovarium. In deltamethrin group, hyperplasic cells, degenerative follicles, pyknotic nuclei, inflammation and hemorrhagic areas were observed. Nebivolol treatment restored these pathologies. Deltamethrin treatment increased TNF-α and PCNA reaction. However, nebivolol decreased the expression. Conclusions: It was thought that deltamethrin toxicity adversely affected follicle development by inducing degeneration and apoptotic process in preantral and antra follicle cells, and nebivolol administration might reduce inflammation and slow down the apoptotic signal in the nuclear phase and regulate reorganization.

Computational study of therapeutic potential of phosphorene as a nano-carrier for drug delivery of nebivolol for the prohibition of cardiovascular diseases: a DFT study.

Density functional theory (DFT) calculations were utilized to assess the drug delivery efficiency of phosphorene carrier for nebivolol drug to treat cardiovascular diseases. The optimized structures, excited state, and electronic properties of nebivolol, phosphorene, and nebivolol-phosphorene (nebivolol-PH) complex were considered to determine the drug delivery ability of phosphorene at the target site. The increased dipole moment (6.08 D) results in the higher solubility of the complex in polar solvents (water). Weak interactive forces between nebivolol and phosphorene were demonstrated by the non-covalent interaction (NCI) plot that facilitated the offloading of nebivolol at the targeted area. The analysis of frontier molecular orbitals (FMOs) revealed that during excitation, the charge was transferred from nebivolol as a higher occupied molecular orbital (HOMO) to phosphorene as a lower unoccupied molecular orbital (LUMO). Thus, the charge-transfer process was further studied by charge decomposition analysis (CDA). The calculated results at the excited state for the nebivolol-PH complex exhibited that the maximum wavelength (λmax) was red-shifted by 6 nm in the gas phase. The electron-hole theory and photoinduced electron transfer (PET) processes were carried out for the exploration of different excited states of the complex. Additionally, phosphorene with + 1 and - 1 charge states indicated the minor structural changes and provide the stable nebivolol-PH complex. This theoretical study also investigated that phosphorene can be exploited as an effective carrier for the delivery of a therapeutic agent as nebivolol to treat cardiovascular diseases. This work will also encourage the researchers to investigate the other 2D nanoparticles as a nano-drug delivery system (NDDS).

Protective effects of Nebivolol against interleukin-1ß (IL-1ß)-induced type II collagen destruction mediated by matrix metalloproteinase-13 (MMP-13).

The pathological progression of osteoarthritis (OA) involves degradation of articular cartilage matrix. Type II collagen is the main component of cartilage matrix, which is degraded by pro-inflammatory cytokines such as IL-1ß mediated by MMP-13. Nebivolol, a licensed drug used for the treatment of hypertension in clinics, displays its anti-inflammatory capacity in various conditions. However, whether Nebivolol has a protective effect on cartilage matrix degradation has not been reported before. In this study, we investigated the effects of Nebivolol on regulating the expression of MMP-13 and degradation of type II collagen. Our results indicate that Nebivolol alleviated the increase in gene expression, protein expression, and activity of MMP-13 induced by IL-1ß. Importantly, IL-1ß strikingly reduced the levels of type II collagen in cell culture supernatants, which was reversed by treatment with Nebivolol in a dose-dependent manner. Mechanistically, Nebivolol was found to alleviate the increased levels of phosphorylated IκBα and reduced levels of total IκBα induced by IL-1ß, which subsequently mitigated p65 nuclear translocation and the transcriptional activity of NF-κB. Furthermore, our results indicated that IL-1ß treatment resulted in a significant increase in expression of the transcriptional factor interferon regulatory factor-1 (IRF-1) at both the mRNA and protein levels, which was significantly ameliorated by treatment with Nebivolol. The combination of these findings suggests that Nebivolol can potentially be applied in human OA treatment.

Nebivolol-Loaded Microsponge Gel for Healing of Diabetic Wound.

An attempt was made to formulate nebivolol-loaded microsponge gel to access drug at wound area, incorporated into gel that possess optimum moist wound management environment during later stages of wound closure. Nebivolol, antihypertensive drug, exhibits vasodilating effects via nitric oxide pathway, slows diabetic neuropathy, and restores endothelial function in diabetic wounds. Microsponges were prepared by optimizing independent variables; drug to polymer ratio and internal phase volume and their effects on production yield, entrapment efficiency, and particle size. Formulations of microsponges were evaluated for drug content. Differential scanning calorimetry indicated reduction in crystallinity of NB during the formation of microsponges. In vitro study (drug to polymer 1:4 and 10 ml internal phase volume acetone) showed 80% drug released within 8 h. Spherical and porous microsponges confirmed by scanning electron microscopy were incorporated in the carbopol 934 (2%) gel base. Gel was characterized for pH, viscosity, and drug content. Less spreadability determined by texture analyzer demonstrated viscous nature of gel. In vitro diffusion study revealed entrapped drug in porous microsponges with slow release to heal wound. In vivo study performed using streptozotocin-induced diabetic rats and excision wound model showed wound healing and closure activity within day 10. Histology revealed inflammatory cell infiltrations and neovascularization in granulation tissues, ultimately healing wound. Microsponge gel prolonged drug release due to entrapped form in porous structure of microsponges with significant and fast wound healing and closure in diabetic rats. Microsponges with loaded drug fulfilled accessibility at wound area, while gel provided optimum moist wound management environment during later stages of wound closure.

Effect of nebivolol on liver regeneration in an experimental 70% partial hepatectomy model.

BACKGROUND: Factors affecting liver regeneration are still relevant. The purpose of this study is to investigate the effect of nebivolol treatment on liver regeneration in rats in which 70% partial hepatectomy was performed. METHODS: Three groups were created: the control group, the low dose group, and the high dose group, with 20 rats in each group and 70% hepatectomy was performed in all rats. Immediately after partial liver resection, 2 mL physiological saline solution was administered to the control group via oral gavage, 0.5 mg/kg nebivolol was administered via oral gavage to the low dose group and 2 mg/kg nebivolol was administered via oral gavage to the high dose group. On the 1st and 5th days after liver resection, 10 subjects were sacrificed from each group, and liver weights and the mitotic count and Ki-67 were measured. RESULTS: Regenerating liver weight on the 1st and 5th days after partial hepatectomy was statistically different in the low dose and high dose nebivolol groups compared to the control group. Mitotic count on the 1st day after partial hepatectomy was significantly higher in the low dose and high dose nebivolol groups than the control group. There was no statistically significant difference detected between the three groups for the 5th day. On the 1st day, Ki-67 rates were significantly higher in both groups given nebivolol than the control group. However, 5th day results were not statistically significant. CONCLUSION: Nebivolol increases regeneration after partial hepatectomy in rats.

Nebivolol compared with metoprolol for erectile function in males undergoing coronary artery bypass graft.

OBJECTIVE: The aim of this study was to evaluate erectile function in males undergoing coronary artery bypass graft (CABG) while on two different adrenoceptor beta-blocker regimens, namely nebivolol and metoprolol. We hypothesize that the negative effects of cardiopulmonary bypass on erectile function may be possibly attenuated by preferring a vasodilating selective ß1-blocker, nebivolol, to metoprolol as an anti-ischemic and antiarrhythmic agent in males undergoing CABG. METHODS: This randomized, double-blind, prospective clinical study was conducted in patients scheduled for CABG surgery between February 2012 and June 2014. A total of 60 consecutive patients who met inclusion criteria were randomized and divided into the following two groups: N group, which received 5 mg of nebivolol orally for 2 weeks before surgery plus 12 weeks after surgery or M group, which received 50 mg of metoprolol orally for the same period. All patients were evaluated by the erectile function domain of the International Index of Erectile Function-5 (IIEF-5) at the time of admission (before starting the beta-blocker) and 3 months after surgery. RESULTS: In the metoprolol group, the mean IIEF-5 score decreased significantly from a baseline of 15.2±5.8 to 12.9±5.8 (p<0.001), but in the nebivolol group, this difference was not significant (from a baseline 12.9±5.5 to 12.4±5.5, p=0.053). In all patients, the mean IIEF-5 score decreased significantly from a baseline of 14.0±5.7 to 12.6±5.6 (p<0.001). CONCLUSION: Although erectile function in males undergoing CABG surgery decreases when metoprolol is used, nebivolol exerts protective effects on erectile function against the disruptive effects of cardiopulmonary bypass in patients undergoing CABG.

Efectividad y seguridad de nebivolol como tratamiento ambulatorio de primera línea para isquemia miocárdica, no complicada, en adultos / Effectiveness and safety of nebivolol as a first-line outpatient treatment for uncomplicated myocardial ischemia in adults

Antecedentes: Descripción de la condición de salud de interés (indicación): La isquemia miocárdica es un problema causado por el estrechamiento de las arterias que irrigan el corazón. Cuando hay obstrucciones en las arterias, se disminuye el flujo de sangre y oxígeno que irriga el músculo cardiaco. En el momento en que \r\naumentan los requerimientos de oxígeno, como con el ejercicio, el corazón no puede satisfacer la demanda del mismo, por lo cual se generan los síntomas. La cardiopatía isquémica es un síndrome que abarca una serie de patologías que incluyen: la angina estable e inestable, síndrome coronario agudo, y la cardiopatía isquémica crónica. Descripción de la tecnología: El nebivolol es un beta bloqueador selectivo ß-1 de los receptores cardíacos, posee acción vasodilatadora, su acción es prolongada. Es empleado en el tratamient o de la hipertensión arterial, angina de pecho, insuficiencia cardíaca congestiva. Evaluación de efectividad y seguridad: Pregunta de evaluación: En adultos mayores de 18 años con isquemia miocárdica, no complicada¿ Cuál es la efectividad y seguridad de nebivolol comparado con metoprolol como tratamiento ambulatorio de primer a línea? La pregunta de investigación fue refinada y validada con base en: autorización de mercadeo de la tecnología para la indicación de interés (registro sanitario INVIMA), listado de medicamentos vitales no disponibles, cobertura de las tecnologías en el Plan Obligatorio de Salud (POS) (Acuerdo 029 de 2011), revisión de grupos terapéuticos (código ATC: Anatomical, Therapeutic, \r\nChemical classification system), recomendaciones de guías de práctica clínica actualizadas, disponibilidad de evidencia sobre efectividad y seguridad (reportes de evaluación de tecnologías, revisiones sistemáticas de la literatura), uso de las tecnologías (listas nacionales de recobro, estadísticas de prescripción, etc), consulta con expertos temáticos (especialistas clínicos), y otros actores clave. No se identificaron otros comparadores relevantes para la evaluación. Población: Adultos mayores de 18 años con \r\nisquemia miocárdica, no complicada. Tecnología de interés: Nebivolol. Metodología: Búsqueda de literatura, Búsqueda en bases de datos electrónicas. Conclusiones: Efectividad: no se identificó evidencia de efectividad que describa el uso de nebivolol comparado con metoprolol para el tratamiento de la isquemia miocárdica. \r\nSeguridad: no se identificó evidencia de seguridad que describa el uso de nebivolol comparado con metoprolol para el tratamiento de la isquemia miocárdica. Costo-efectividad: no se identificaron estudios de costo-efectividad para Colombia.