•Myricitrin decreased hepatic lipid peroxidation and increased GSH and CYP2E1 level.•Myricitrin reduced COX-2 and TNF-α overexpression and inflammation in the liver.•Myricitrin inhibited hepatic ...expression of TGF-β1 and α-SMA and liver fibrosis.•Myricitrin increased PCNA expression in regenerating liver tissue.
Myricetin-3-O-α-rhamnoside (myricitrin) is a naturally occurring phenolic compound which possesses antioxidant and anti-inflammatory activity. The aim of this study was to determine the hepatoprotective effects of myricitrin. Myricitrin at doses of 10, 30 and 100mg/kg and silymarin at dose of 100mg/kg were administered to BALB/cN mice by oral gavage, once daily for two consecutive days following carbon tetrachloride (CCl4)-intoxication. Myricitrin significantly ameliorated CCl4-induced increase in serum aspartate transaminase (AST) and alanine transaminase (ALT) levels and histopathological changes in the liver. Hepatic oxidative stress was reduced by myricitrin, as evidenced by the decrease in lipid peroxidation, with concomitant increase in glutathione (GSH) level and cytochrome P450 2E1 (CYP2E1) expression. In addition, cyclooxygenase-2 (COX-2) and tumor necrosis factor-alpha (TNF-α) overexpression in the liver was reduced, suggesting the suppression of inflammation. The expression of transforming growth factor-beta1 (TGF-β1) and alpha-smooth muscle actin (α-SMA) was markedly ameliorated, indicating the inhibition of profibrotic response. Myricitrin also improved the regeneration of hepatic tissue after CCl4-intoxication, as evidenced by increased proliferating cell nuclear antigen (PCNA) expression. The results of the current study suggest that myricitrin exhibits a significant hepatoprotective activity. Myricitrin provided better hepatoprotection when compared to silymarin, which is consistent with its higher in vitro antioxidant potential.
Low-intensity pulsed ultrasound (LIPUS) is a form of ultrasound that utilizes low-intensity pulsed waves. Its effect on bones that heal by intramembranous ossification has not been sufficiently ...investigated. In this study, we examined LIPUS and the autologous bone, to determine their effect on the healing of the critical-size bone defect (CSBD) of the rat calvaria. The bone samples underwent histological, histomorphometric and immunohistochemical analyses. Both LIPUS and autologous bone promoted osteogenesis, leading to almost complete closure of the bone defect. On day 30, the bone volume was the highest in the autologous bone group (20.35%), followed by the LIPUS group (19.12%), and the lowest value was in the control group (5.11%). The autologous bone group exhibited the highest intensities of COX-2 (167.7 ± 1.1) and Osx (177.1 ± 0.9) expression on day 30. In the LIPUS group, the highest intensity of COX-2 expression was found on day 7 (169.7 ±1.6) and day 15 (92.7 ± 2.2), while the highest Osx expression was on day 7 (131.9 ± 0.9). In conclusion, this study suggests that LIPUS could represent a viable alternative to autologous bone grafts in repairing bone defects that are ossified by intramembranous ossification.
Highlights • Chlorogenic acid attenuated cisplatin-induced renal oxidative stress by reducing the expression of 4-HNE, HO-1 and CYP2E1. • The inhibition of inflammatory response was achieved through ...the reduction of TNF-α and COX-2 expression. • The expression of p53, Bax, active caspase-3 and LC3B was suppressed, suggesting the inhibition of apoptosis and autophagy. • Attenuation of Mrp1 and Mrp2 expression and the increase in Oct2 expression indicated reduced burden of tubular cells. • The recovery of kidneys form cisplatin injury was accompanied by the suppression of cyclin D1 and augmented PCNA expression.
The aim of this study was to investigate the effects of flavone luteolin against cisplatin (CP)-induced kidney injury in mice. Luteolin at doses of 10mg/kg was administered intraperitoneally (ip) ...once daily for 3 days following single CP (10 or 20mg/kg) ip injection. Mice were sacrificed 24h after the last dose of luteolin. The CP treatment significantly increased serum creatinine and blood urea nitrogen and induced pathohistological changes in the kidneys. Renal oxidative/nitrosative stress was evidenced by decreased glutathione (GSH) levels and increased 3-nitrotyrosine (3-NT) and 4-hydroxynonenal (4-HNE) formation as well as cytochrome P450 2E1 (CYP2E1) expression. The CP administration triggered inflammatory response in mice kidneys through activation of nuclear factor-kappaB (NF-κB) and overexpression of tumor necrosis factor-alpha (TNF-α) and cyclooxygenase-2 (COX-2). Simultaneously, the increase in renal p53 and caspase-3 expression indicated apoptosis of tubular cells. The administration of luteolin significantly reduced histological and biochemical changes induced by CP, decreased platinum (Pt) levels and suppressed oxidative/nitrosative stress, inflammation and apoptosis in the kidneys. These results suggest that luteolin is an effective nephroprotective agent, with potential to reduce Pt accumulation in the kidneys and ameliorate CP-induced nephrotoxicity.
Xenogeneic biomaterials Cerbone® and OsteoBiol® are widely used in oral implantology. In dental practice, xenogeneic biomaterial is usually combined with autologous bone to provide bone volume ...stability needed for long-term dental implants. Magnesium alloy implants dissolve and form mineral corrosion layer that is directly in contact with bone tissue, allowing deposition of the newly formed bone. CSBD heals by intramembranous ossification and therefore is a convenient model for analyses of ostoconductive and osteoinductive properties of different type of biomaterials. Magnesium alloy-enriched biomaterials have not yet been applied in oral implantology. Therefore, the aim of the current study was to investigate biological properties of potentially new bovine xenogeneic biomaterial enriched with magnesium alloy in a 5 mm CSBD model. Osteoconductive properties of Cerabone®, Cerabone® + Al. bone, and OsteoBiol® were also analyzed. Dynamics of bone healing was followed up on the days 3, 7, 15, 21, and 30. Calvary bone samples were analyzed by micro-CT, and values of the bone morphometric parameters were assessed. Bone samples were further processed for histological and immunohistochemical analyses. Histological observation revealed CSBD closure at day 30 of the given xenogeneic biomaterial groups, with the exception of the control group. TNF-α showed high intensity of expression at the sites of MSC clusters that underwent ossification. Osx was expressed in pre-osteoblasts, which were differentiated into mature osteoblasts and osteocytes. Results of the micro-CT analyses showed linear increase in bone volume of all xenogeneic biomaterial groups and also in the control. The highest average values of bone volume were found for the Cerabone® + Mg group. In addition, less residual biomaterial was estimated in the Cerabone® + Mg group than in the Cerabone® group, indicating its better biodegradation during CSBD healing. Overall, the magnesium alloy xenogeneic biomaterial demonstrated key properties of osteoinduction and biodegradidibility during CSBD healing, which is the reason why it should be recommended for application in clinical practice of oral implantology.
Autologous dentin is frequently used in guided bone regeneration due to its osteoinductive properties, which come from its similarity to native bone. On the other hand, the xenogeneic bone ...biomaterial Cerabone
serves as a biocompatible, but hardly resorbed biomaterial. During bone healing, an inflammatory, vascular, and osteogenic response occurs in which cytokines such as tumor necrosis factor-alpha (TNF-α), vascular endothelial growth factor (VEGF), and osteopontin (OPN) are released locally and systemically. The aim was to follow up the dynamics (on days 3, 7, 15, 21, and 30) of critical-sized bone defect (CSBD) healing after the implantation of bovine devitalized dentin, rat dentin, and xenogeneic bone biomaterial. For this purpose, histological and histomorphometric methods were employed. Additionally, serum concentrations of TNF-α, VEGF, and OPN were monitored in parallel to better understand the biomaterial-dependent systemic response in rats. At the last time interval, the results showed that the bone defect was bridged over in all three groups of biomaterials. The rat dentin group had the highest percentage of bone volume (BV/TV) and the least percentage of residual biomaterial (RB), which makes it the most optimal biomaterial for bone regeneration. Serum concentrations of the TNF-α, VEGF, and OPN refer to systemic response, which could be linked to intense bone remodeling between days 15 and 21 of the bone healing.
► CCl4-intoxication caused a severe liver damage in mice. ► Rosmarinic acid significantly ameliorated oxidative/nitrosative stress and apoptosis in the liver. ► Rosmarinic acid significantly ...suppressed inflammatory response in the liver. ► Rosmarinic acid prevented hepatic stellate cells activation and fibrogenesis.
The aim of this study was to investigate the therapeutic potential of rosmarinic acid (RA), a natural phenolic, in the treatment of acute liver toxicity. RA at 10, 25 and 50mg/kg was administered by gavage once daily for 2 consecutive days, 6h after CCl4 intoxication. CCl4 intoxication caused hepatic necrosis and increased serum ALT activity. In the livers, oxidative/nitrosative stress was evidenced by increased 3-nitrotyrosine (3-NT) and thiobarbituric acid reactive substances (TBARS) formation and a significant decrease in Cu/Zn superoxide dismutase (SOD) activity. CCl4 administration triggered inflammatory response in mice livers by activating nuclear factor-kappaB (NF-κB), which coincided with the induction of tumor necrosis factor-alpha (TNF-α) and cyclooxygenase-2 (COX-2). RA improved histological and serum markers of liver damage and significantly ameliorated oxidative/nitrosative stress and inflammatory response in liver tissue. Additionally, RA prevented transforming growth factor-beta1 (TGF-β1) and alpha-smooth muscle actin (α-SMA) expression, suggesting suppression of profibrotic response. Furthermore, RA significantly inhibited the CCl4-induced apoptosis, which was evident from decreased cleavage of caspase-3. The hepatoprotective activity of RA coincided with enhanced NF-E2-related factor 2 (Nrf2) and heme oxygenase-1 (HO-1) expression. The results of this study indicates that RA possesses antioxidant, anti-inflammatory, antiapoptotic and antifibrotic activity against acute liver toxicity.
A certain percentage of carpal tunnel syndrome (CTS) is associated with inflammatory conditions. Osteoarthritis (OA) increases the risk of CTS, and both diseases are common in the general population. ...Moreover, OA and CTS are often present in the same patients. Since inflammation and fibrosis are found in both conditions, the question is whether circulating inflammatory cytokines and cytokines involved in fibrosis in OA and CTS patients could serve as indicators of coexisting CTS and OA pathology. This investigation was performed on 31 CTS patients, 29 hip OA patients, and 15 healthy volunteers. Blood samples were collected, and serum levels of TGF-β1, BMP-7, IL-1β, and TNFα were measured using the ELISA method. The statistical analysis was performed to reveal the most significant differences in the serum levels of these cytokines. Statistical significance was set at p-values ≤ 0.05. The serum level of TGF-β1 was the highest in CTS patients (16.36 pg/mL) and significantly different compared to OA and healthy control. Analysis of the cytokine serum level in the subdivided group revealed that serum levels of TGF-β1 and BMP-7 were significantly higher in CTS+/OA+ patients as well as BMP-7 in the OA+/CTS+ group. There was no significant difference in serum levels of the inflammatory cytokines TNFα and IL-1β among all groups. This study showed that in the end stage of CTS and OA, serum levels of inflammatory cytokines (IL1-β and TNFα) were not altered, while the serum levels of TGF-β1 and BMP-7 were significantly higher, especially in patients with coexisting OA and CTS. These findings suggest the possible values of TGF-β1 and BMP-7 as a predictive factor for the comorbidity of CTS and OA.
The aim of this study was to determine the prevalence of usage and the knowledge and attitudes towards dietary supplements among medical sciences and nonmedical sciences students from Croatia. The ...study was conducted based on a questionnaire about dietary supplement usage, knowledge and attitudes. The prevalence of dietary supplement use, among 910 university students was 30.5%. The most-used dietary supplements were vitamins (18.0% in medical sciences students and 9.8% in non-medical sciences students). For all students, the internet (66.1%) was the most common source of information, followed by healthcare professionals (33.2%). The most common reason for taking dietary supplements was to maintain good health (26.4%). Use of the internet rather than health professionals as a trusted information source should be revised among this young population. Supplement intake was significantly associated with body mass index (BMI) (
= 0.016) and physical activity (
= 0.050). Students with normal BMI (61.5%) and the most physically active students (37.7%) took significantly more dietary supplements. Results of this study could help medicine faculties to improve their curriculum and support the development of public health messages aimed at wise and safe use of dietary supplements.
Bacterial contamination of the membranes used during guided bone regeneration directly influences the outcome of this procedure. In this study, we analyzed the early stages of bacterial adhesion on ...two commercial dense polytetrafluoroethylene (d-PTFE) membranes in order to identify microstructural features that led to different adhesion strengths. The microstructure was investigated by X-ray diffraction (XRD), differential scanning calorimetry (DSC), and Fourier transform infrared (FTIR). The surface properties were analyzed by atomic force microscopy (AFM), scanning electron microscopy (SEM), and surface free energy (SFE) measurements. Bacterial properties were determined using the microbial adhesion to solvents (MATS) assay, and bacterial surface free energy (SFE) was measured spectrophotometrically. The adhesion of four species of oral bacteria (
,
,
, and
) was studied on surfaces with or without the artificial saliva coating. The results indicated that the degree of crystallinity (78.6% vs. 34.2%, with average crystallite size 50.54 nm vs. 32.86 nm) is the principal feature promoting the adhesion strength, through lower nanoscale roughness and possibly higher surface stiffness. The spherical crystallites ("warts"), observed on the surface of the highly crystalline sample, were also identified as a contributor. All bacterial species adhered better to a highly crystalline membrane (around 1 log
CFU/mL difference), both with and without artificial saliva coating. Our results show that the changes in polymer microstructure result in different antimicrobial properties even for chemically identical PTFE membranes.
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