RESUMO
The Mediterranean diet, which is characterized by high consumption of olive oil, prevents cardiovascular disease. Meanwhile, olive mill wastewater (OMWW), which is obtained as a byproduct during olive oil production, contains various promising bioactive components such as water-soluble polyphenols. Hydroxytyrosol (HT), the major polyphenol in OMWW, has anti-oxidative and anti-inflammatory properties; however, the atheroprotective effects of OMWW and HT remain to be fully understood. Here, we investigated the effect of OMWW and HT on atherogenesis. Male 8-week-old apolipoprotein E-deficient mice were fed a western-type diet supplemented with OMWW (0.30%w/w) or HT (0.02%w/w) for 20 weeks. The control group was fed a non-supplemented diet. OMWW and HT attenuated the development of atherosclerosis in the aortic arch as determined by Sudan IV staining (P < 0.01, respectively) without alteration of body weight, plasma lipid levels, and blood pressure. OMWW and HT also decreased the production of oxidative stress (P < 0.01, respectively) and the expression of NADPH oxidase subunits (e.g., NOX2 and p22phox) and inflammatory molecules (e.g. IL-1ß and MCP-1) in the aorta. The results of in vitro experiments demonstrated that HT inhibited the expression of these molecules that were stimulated with LPS in RAW264.7 cells, murine macrophage-like cells. OMWW and HT similarly attenuated atherogenesis. HT is a major component of water-soluble polyphenols in OMWW, and it inhibited inflammatory activation of macrophages. Therefore, our results suggest that the atheroprotective effects of OMWW are at least partially attributable to the anti-inflammatory effects of HT.
Assuntos
Aterosclerose , Olea , Camundongos , Masculino , Animais , Águas Residuárias , Olea/química , Azeite de Oliva/farmacologia , Azeite de Oliva/química , Aterosclerose/prevenção & controle , Anti-Inflamatórios/farmacologia , Polifenóis/farmacologia , Polifenóis/química , Água , ApolipoproteínasRESUMO
Objectives: An anterior bite plane (ABP) is an orthodontic appliance that prevents posterior teeth from making contact. This appliance's functional concept is to reduce muscle activity, overcome deep overbite, and temporomandibular joint (TMJ) disorders (TMD). However, ABP treatment for malocclusion frequently results in unfavorable reversible and irreversible long-term effects. This problem presents difficulties for dentists in developing an appropriate treatment modification plan in order to achieve the best results. As a result, the goal of this study is to observe the effects of different ABP types on the TMJ and mandible. Materials and Methods: Thirty-six three-month-old male Wistar strain rats were divided into three groups: control, upper flat, and upper-lower inclined ABP. The overbite and body weight were measured. TMJ was examined histologically using hematoxylin and eosin (HE). To observe the entire mandibular bone in response to ABP, mandibular planes and angulations were measured. Results: After 7 days, the upper-lower inclined ABP group has significantly lower body weight than the control group. On days 7 and 14, overbite was significantly reduced in both the upper flat and upper-lower inclined ABP groups. The superficial layer of the condyle was depleted in both ABP groups, according to HE analysis. Mandibular angle analysis revealed that the upper-lower inclined ABP group had a greater incisal and ramus angle. Furthermore, lower incisor (Li)-condyle (Co) mandibular points increased significantly more in the upper-lower inclined ABP group than in the control group. Conclusion: According to this study, various forms of ABP may have an impact on the TMJ and mandibular morphology, specifically on the length, angulation, and superficial surface of the condyle.
RESUMO
AIM: Recent studies have demonstrated that selective sodium-glucose cotransporter 2 inhibitors (SGLT2is) reduce cardiovascular events, although their mechanism remains obscure. We examined the effect of canagliflozin, an SGLT2i, on atherogenesis and investigated its underlying mechanism. METHOD: Canagliflozin (30 mg/kg/day) was administered by gavage to streptozotocin-induced diabetic apolipoprotein E-deficient (ApoEï¼/ï¼) mice. Sudan IV staining was performed at the aortic arch. Immunostaining, quantitative RT-PCR, and vascular reactivity assay were performed using the aorta. In vitro experiments using human umbilical vein endothelial cells (HUVECs) were also performed. RESULT: Canagliflozin decreased blood glucose (Pï¼0.001) and total cholesterol (Pï¼0.05) levels. Sudan IV staining showed that 12-week canagliflozin treatment decreased atherosclerotic lesions (Pï¼0.05). Further, 8-week canagliflozin treatment ameliorated endothelial dysfunction, as determined by acetylcholine-induced vasodilation (Pï¼0.05), and significantly reduced the expressions of inflammatory molecules such as ICAM-1 and VCAM-1 in the aorta at the RNA and protein levels. Canagliflozin also reduced the expressions of NADPH oxidase subunits such as NOX2 and p22phox in the aorta and reduced urinary excretion of 8-OHdG, suggesting a reduction in oxidative stress. Methylglyoxal, a precursor of advanced glycation end products, increased the expressions of ICAM-1 and p22phox in HUVECs (Pï¼0.05, both). Methylglyoxal also decreased the phosphorylation of eNOSSer1177 and Akt but increased the phosphorylation of eNOSThr495 and p38 MAPK in HUVECs. CONCLUSION: Canagliflozin prevents endothelial dysfunction and atherogenesis in diabetic ApoEï¼/ï¼ mice. Anti-inflammatory and antioxidative potential due to reduced glucose toxicity to endothelial cells might be its underlying mechanisms.
Assuntos
Apolipoproteínas E/genética , Canagliflozina/farmacologia , Complicações do Diabetes/tratamento farmacológico , Doenças Vasculares/tratamento farmacológico , Animais , Aorta/efeitos dos fármacos , Aterosclerose/tratamento farmacológico , Diabetes Mellitus Experimental , Endotélio Vascular/efeitos dos fármacos , Células Endoteliais da Veia Umbilical Humana , Humanos , Imuno-Histoquímica , Técnicas In Vitro , Inflamação , Masculino , Camundongos , Camundongos Endogâmicos C57BL , Estresse Oxidativo , Inibidores do Transportador 2 de Sódio-Glicose/farmacologiaRESUMO
Diabetic patients have coagulation abnormalities, in which thrombin plays a key role. Whereas accumulating evidence suggests that it also contributes to the development of vascular dysfunction through the activation of protease-activated receptors (PARs). Here we investigated whether the blockade of thrombin attenuates endothelial dysfunction in diabetic mice. Induction of diabetes by streptozotocin (STZ) increased the expression of PAR1, PAR3, and PAR4 in the aorta. STZ-induced diabetic mice showed impairment of endothelial function, while the administration of dabigatran etexilate, a direct thrombin inhibitor, significantly attenuated endothelial dysfunction in diabetic mice with no alteration of metabolic parameters including blood glucose level. Dabigatran did not affect endothelium-independent vasodilation. Dabigatran decreased the expression of inflammatory molecules (e.g., MCP-1 and ICAM-1) in the aorta of diabetic mice. Thrombin increased the expression of these inflammatory molecules and the phosphorylation of IκBα, and decreased the phosphorylation of eNOSSer1177 in human umbilical endothelial cells (HUVEC). Thrombin significantly impaired the endothelium-dependent vascular response of aortic rings obtained from wild-type mice. Inhibition of NF-κB attenuated thrombin-induced inflammatory molecule expression in HUVEC and ameliorated thrombin-induced endothelial dysfunction in aortic rings. Dabigatran attenuated the development of diabetes-induced endothelial dysfunction. Thrombin signaling may serve as a potential therapeutic target in diabetic condition.