Administration Of Resveratrol Research Articles

The effects of resveratrol and quercetin administration in experimental pleural inflammation

The effects of resveratrol and quercetin administration in experimental pleural inflammation

The Histological and Immunohistochemical Study of Tramadol Induced Testicular Toxicity and Protective Effects of Resveratrol in Adult Male Albino Rats

Background and Objectives: Tramadol is a centrally acting analgesic drug. Chronic intake of Tramadol has negative impactson testis. Resveratrol is considered to be a natural compound that has antioxidant and anti-inflammatory effects.Aim : The present study was designed to monitor the impacts of the use of Tramadol on the testis of adult male albino rats andthe beneficial effects of Resveratrol.Materials and Methods: 40 adult male albino rats were classified randomly into 4 groups. Each one inclued10 rats as follows:Group I (control group): received 0.1 ml of physiological saline solution. Group II: received Resveratrol 20 mg/kg/day orallyfor 4 weeks. Group III: (Tramadol-treated group): received Tramadol 50 mg/kg/day orally for 4 weeks. GroupIV: receivedTramadol 50 mg/kg body weight daily orally followed byResveratrol 20 mg/kg body weight daily by intragastric gavage for 4 week. Blood samples were obtained to assess serumlevels of testosterone, FSH and LH. Testes were removed and prepared for histological examination and immunohistochemicalstaining. The experimental data were analyzed using IBM SPSS Statistics software.Results: Tramadol-treated group showed severe distortion of the testicular structure in which many seminiferous tubuleswere degenerated with losing their normal histological architecture. Meanwhile, sections of testes of group IV (Tramadol–Resveratrol treated group) showed nearly normal histology. Positive immune-reactivity for PCNA in the control, Resveratroltreated and Tramadol - Resveratrol treated groups while, Tramadol- treated group showed few positive immuno-reactivity forPCNA. Serum LH, FSH and testosterone hormones levels were significantly higher in Tramadol-Resveratrol treated group compared to Tramadol treated group.Conclusion: Intake of Tramadol induced testicular damage which can be ameliorated by administration of Resveratrol in theconcomitant with Tramadol treatment.

Effects of resveratrol on alpha-amanitin-induced nephrotoxicity in BALB/c mice.

Alpha-amanitin (α-AMA), the primary toxin of Amanita phalloides, is known to cause nephrotoxicity and hepatotoxicity. Resveratrol is an antioxidant that has shown efficacy in many nephrotoxicity models. The aim of this study was to investigate the effects of resveratrol against the early and late stages of α-AMA-induced nephrotoxicity, compared to those of silibinin, a well-known antidote for poisoning by α-AMA-containing mushrooms. Mice kidney tissues were obtained from five groups: (1) α-AMA + NS (simultaneous administration of α-AMA and normal saline), (2) α-AMA + SR (simultaneous administration of α-AMA and resveratrol), (3) α-AMA + 12R (resveratrol administration 12 h after α-AMA administration), (4) α-AMA + 24R (resveratrol administration 24 h after α-AMA administration), and (5) α-AMA + Sil (simultaneous administration of α-AMA and silibinin). Histomorphological and biochemical analyses were performed to evaluate kidney damage and oxidant-antioxidant status in the kidney. Scores of renal histomorphological damage decreased significantly in the early resveratrol treatment groups (α-AMA + SR and α-AMA + 12R), compared to those in the α-AMA + NS group (p < 0.05). Catalase levels increased significantly in the α-AMA + SR group, compared to those in the α-AMA + NS group (p < 0.001). Early resveratrol administration within 12 h after α-AMA ingestion may reverse the effects of α-AMA-induced nephrotoxicity, partly through its antioxidant action, thereby suggesting its potential as a treatment for poisoning by α-AMA-containing mushrooms.

Resveratrol suppresses nociceptive jaw-opening reflex via 5HT3 receptor-mediated GABAergic inhibition

Systemic administration of the dietary constituent, resveratrol, was previously shown to inhibit the nociceptive jaw-opening reflex (JOR) via the endogenous opioid system. The present study investigated whether resveratrol could similarly affect the JOR under in vivo conditions via 5HT3 receptor-mediated GABAergic inhibition. We used electrical stimulation of the tongue in pentobarbital-anesthetized rats to evoke the JOR, which was recorded as the anterior belly of the digastric muscle electromyograms (dEMG). Intravenous administration of resveratrol (2 mg/kg) reduced the dEMG amplitude in response to three times the determined threshold electrical stimulation, with maximum inhibition reached within approximately 10 min. These inhibitory effects on the JOR were reversible to control levels after approximately 20 min. Pretreatment of rats with either 5HT3 receptor antagonist, ondansetron (0.25−1 mg/kg, i.p.), or GABAA receptor antagonist, bicuculline (0.5−1 mg/kg, i.p.), significantly and dose-dependently attenuated the inhibitory effects of resveratrol on dEMG amplitude compared with untreated controls. These findings suggest that resveratrol also attenuates the nociceptive JOR via 5HT3 receptor-mediated GABAergic inhibition. The present study therefore provides new insight into a possible mechanism underlying resveratrol-induced trigeminal antinociception via the descending pain control system and highlights a potential therapeutic agent for complementary alternative medicine.

Resveratrol Attenuates Pressure Overload-Induced Cardiac Fibrosis and Diastolic Dysfunction via PTEN/AKT/Smad2/3 and NF-κB Signaling Pathways.

Cardiac fibrosis is a key feature of cardiac remodeling. Recently, a protective role for resveratrol (RES) in pressure-overload-induced cardiac hypertrophy and contractile dysfunction has been demonstrated. However, the effect of RES on cardiac fibrosis and diastolic function in this model remains unclear. Cardiac remodeling is induced in mice by transverse aortic constriction (TAC) for 2-4 weeks. RES is administered at dose of 5 or 50mgkg-1 d-1 for 2 weeks. It is found that RES administration at 50mgkg-1 d-1 significantly attenuates TAC-induced adverse cardiac systolic and diastolic function, fibrosis, inflammation, and oxidative stress via inhibiting PTEN degradation and the downstream mediators. However, RES at 5mgkg-1 d-1 has no significant effects. RES at 50mgkg-1 d-1 also ameliorates pre-established adverse cardiac function and remodeling induced by TAC. Treatment with PTEN inhibitor VO-OHpic (10mgkg-1 d-1 ) for 2 weeks abolishes RES-mediated protective effects. Additionally, the effect of RES (100µm) on inhibition of Ang II-induced fibroblast proliferation and activation in vitro is verified. The findings provide new evidence that RES plays a critical role in the progression of cardiac fibrosis and diastolic dysfunction, and suggest that RES may be a promising therapeutic agent for cardiac fibrosis.

Co-administration of resveratrol and beta-aminopropionitrile attenuates liver fibrosis development via targeting lysyl oxidase in CCl4-induced liver fibrosis in rats

Objectives: In the current study, we aimed to investigate the effect of administration of resveratrol (RES) and beta-aminopropionitrile (BAPN) separately and together on the liver fibrosis progression via regulation of the gene expression and protein level of lysyl oxidase (LOX).Materials and methods: The six-week old Wistar rats received carbon tetrachloride (CCl4) intraperitoneally and RES and BAPN were administrated orally for eight weeks. The hepatoprotective effects of RES, BAPN, and combination treatment were evaluated. Then the hepatic protein and gene expression levels of LOX were measured.Results: Both RES and BAPN showed the antifibrotic effect through the reduction of collagen fiber bundles, hepatic hydroxyproline content, and protein level of LOX. The antifibrotic effect increased when RES and BAPN up-taken together.Conclusion: The co-administration of RES and BAPN can be considered as a promising therapeutic approach via targeting LOX.

A novel compound AB38b attenuates oxidative stress and ECM protein accumulation in kidneys of diabetic mice through modulation of Keap1/Nrf2 signaling.

Extracellular matrix (ECM) deposition following reactive oxygen species (ROS) overproduction has a key role in diabetic nephropathy (DN), thus, antioxidant therapy is considered as a promising strategy for treating DN. Here, we investigated the therapeutic effects of AB38b, a novel synthetic α, β-unsaturated ketone compound, on the oxidative stress (OS) and ECM accumulation in type 2 diabetes mice, and tried to clarify the mechanisms underlying the effects in high glucose (HG, 30 mm)-treated mouse glomerular mesangial cells (GMCs). Type 2 diabetes model was established in mice with high-fat diet feeding combined with streptozocin intraperitoneal administration. The diabetic mice were then treated with AB38b (10, 20, 40 mg· kg−1· d−1, ig) or a positive control drug resveratrol (40 mg· kg−1· d−1, ig) for 8 weeks. We showed that administration of AB38b or resveratrol prevented the increases in malondialdehyde level, lactate dehydrogenase release, and laminin and type IV collagen deposition in the diabetic kidney. Simultaneously, AB38b or resveratrol markedly lowered the level of Keap1, accompanied by evident activation of Nrf2 signaling in the diabetic kidney. The underlying mechanisms of antioxidant effect of AB38b were explored in HG-treated mouse GMCs. AB38b (2.5−10 μM) or resveratrol (10 μM) significantly alleviated OS and ECM accumulation in HG-treated GMCs. Furthermore, AB38b or resveratrol treatment effectively activated Nrf2 signaling by inhibiting Keap1 expression without affecting the interaction between Keap1 and Nrf2. Besides, AB38b treatment effectively suppressed the ubiquitination of Nrf2. Taken together, this study demonstrates that AB38b ameliorates experimental DN through antioxidation and modulation of Keap1/Nrf2 signaling pathway.

Inhibition of Opisthorchis felineus glutathione-dependent prostaglandin synthase by resveratrol correlates with attenuation of cholangiocyte neoplasia in a hamster model of opisthorchiasis

Food-borne trematodiases represent major neglected parasitic diseases. Trematodes of the family Opisthorchiidae including Opisthorchis felineus, Opisthorchis viverrini and Clonorchis sinensis are ranked eight on the global list of the 24 most prevalent food-borne parasites. Chronic O. felineus infection symptoms include precancerous lesions with the potential for malignancy. In recent decades, liver flukes of the family Opisthorchiidae have been extensively scientifically explored, however despite this the molecular mechanisms of O. felineus pathogenicity and its carcinogenic potential have not been studied. Opisthorchis felineus glutathione-dependent prostaglandin synthase (GST σ) is the major component of the excretory–secretory product of this liver fluke. We hypothesised that the activity of this enzyme is involved in the infection pathogenesis, including the formation of precancerous lesions. To test this hypothesis and to gain insights into the mechanisms of precancerous lesion formation, we (i) investigated whether excretory parasitic GST σ retains its enzymatic activity, (ii) tested resveratrol (RSV) as a possible inhibitor of this enzyme, and (iii) assessed biliary neoplasia and oxidative DNA damage as well as the expression of neoplasia and fibrogenesis marker genes after prolonged administration of RSV in a hamster model. RSV was found to inhibit GST σ enzymatic activity in a dose-dependent manner (R = 0.85, P < 0.001; half-maximal effective dose (ED50) = 48.6 μM). Prolonged administration of RSV significantly suppressed high-grade biliary neoplasia (P = 0.008), attenuated upregulation of hyperplasia and fibrogenesis-related genes (Tgfb, α-SMA and CK7), and decreased the elevated oxidative DNA damage. Taking into account that RSV can influence a wide range of pathways, further research is needed to confirm the role of GST σ in O. felineus pathogenicity. Nevertheless, the chemopreventive effect of RSV targeting biliary neoplasia formation might be useful for improving the outcomes in infected populations and represents a compelling rationale for RSV testing in combination chemotherapy of opisthorchiasis.

Effects of Carbophos on Rat Testopathy Following Resveratrol Administration: An Experimental Study

Objective: Carbophos (CAR) is an organophosphate that is most capable of producing free radicals and inducing alteration in some of the male reproductive parameters. Resveratrol (RES) is an herbal polyphenol and exerts beneficial antioxidant effects. This study aimed to evaluate the effects of RES against CAR-induced alteration in reproductive parameters of male rats. Methods: In this experimental study, 48 male rats were randomly assigned to eight groups: Group 1: Normal control (saline) group; Group 2: CAR control (250 mg/kg) group; Groups 3–5: 2, 8, and 20 mg/kg RES, respectively, groups; Groups 6–8: CAR plus 2, 8, and 20 mg/kg RES, respectively, groups. The agents were administered intraperitoneally and by gavage daily for 65 days. Sperm parameters, testis malondialdehyde (MDA) levels, total antioxidant capacity, testosterone levels, and germinal layer height were evaluated and compared among these groups. Results: No significant alterations were observed in RES groups (with different doses) compared to the normal control group (P > 0.05). The levels of all parameters except MDA (which decreased) significantly increased in the CAR plus RES (with different doses) groups compared to the CAR control group (P Conclusions: RES attenuates the toxic effect of CAR on some of the male reproductive parameters.

Effects of paclitaxel and resveratrol on blood characteristics in rabbits

ABSTRACTWe investigated the adverse effects of paclitaxel (PAC) on blood characteristics including the percentage of alpha naphthyl acetate esterase (ANAE)-positive peripheral blood lymphocytes, white cell count, number of neutrophil nuclear lobe and, erythrocyte diameter, and the protective effects of resveratrol (RES) on these characteristics. Male New Zealand rabbits were assigned to four groups. The control group (C) was given 40 ml normal saline, the PAC group was given 5 mg/kg PAC in 40 ml normal saline, the RES group was given 4 mg/kg RES in 40 ml normal saline, and the PAC + RES group was given 5 mg/kg PAC + 4 mg/kg RES in 40 ml normal saline. All injections were performed intravenously once/week for 8 weeks. PAC caused an increased total percentage of lymphocytes and monocytes, which was associated with neutropenia. The PAC group showed a right shift in the lobulation curve of neutrophil nuclei together with a decreased percentage of ANAE-positive lymphocytes. RES reduced the percentage of ANAE-positive lymphocytes, slightly increased the percentage of neutrophil leukocytes and reduced the total lymphocyte count. Administration of RES combined with PAC prevented, while PAC induced, neutropenia and lymphocytosis, and increased the percentage of ANAE-positive lymphocytes.

Comparison of the protective efficacy between intratympanic dexamethasone and resveratrol treatments against cisplatin-induced ototoxicity: an experimental study

The main aim of this study was to compare the efficacy of intratympanic administration of dexamethasone and resveratrol in preventing cisplatin ototoxicity by measuring acoustic brainstem response (ABR) and distortion product otoacoustic emission (DPOAE). Forty rats (80 ears) were divided into five groups. Cisplatin was administered intraperitoneally to the first group (n = 8). Group 2 (n = 8) received cisplatin after resveratrol had been administered intratympanically. Group 3 (n = 8) received cisplatin after dexamethasone had been administered intratympanically. Group 4 (n = 8) received cisplatin after sodium chloride (NaCl) had been given intratympanically. Group 5 (n = 8) received cisplatin after dimethylsulfoxide (DMSO) had been given intratympanically. ABR and DPOAE tests were performed on all groups before and 72h after the procedure. ABR threshold values in rats that received dexamethasone and resveratrol were found to be less affected than those observed in the other post-cisplatin groups. ABR-IV and ABR-I-IV interval values were significantly reduced in rats that had been given dexamethasone and resveratrol compared to the other groups. After cisplatin treatment, otoacoustic emission (OAE) amplitudes were significantly decreased in Groups 1, 4, and 5 for all frequencies, while OAE values were sustained in the resveratrol and dexamethasone groups (Groups 2 and 3). At OAE frequency 5652, dexamethasone was more significantly associated with protective than resveratrol was, while no significant difference was found between the two groups at other OAE frequencies. In conclusion, intratympanic dexamethasone and intratympanic resveratrol treatments may provide a significant protection against cisplatin-induced ototoxicity.

The immune-adjuvant activity and the mechanism of resveratrol on pseudorabies virus vaccine in a mouse model

Resveratrol had shown various properties before, like immunomodulatory, anti-inflammatory and antiviral activities. Based on these properties, the present study was designed to evaluate the effects and mechanism of resveratrol as an immune-adjuvant for pseudorabies virus (PRV) vaccine. We found that oral administration of resveratrol to mice significantly increased the number of T lymphocytes in the spleen, and elevated the concentrations of antibodies and cytokines in the serum. Resveratrol (30 mg/kg) could enhance phagocytic capacity of peritoneal macrophage (PM) by boosting the percentage of phagocytosis, phagocytic index and the level of lysozyme. Resveratrol also enhanced antigen presentation function of PM by upregulating the expressions of CD86 and MHC-II. Further study revealed that resveratrol could increase the protein levels of TLR4, Ikk, IκBα, NF-κB and JNK when compared with non-adjuvant group. These results provide further insight into the mechanism of action in adjuvant activity of resveratrol, and also offer preclinical evidence for development as a PRV vaccine adjuvant.

Resveratrol Improves Cardiac Functions of the Diabetic Cardiomyopathy Rats Via Modulation of AMP-Activated Protein Kinase and the Phosphorylated Glycogen Synthase Kinase-3(3

AbstractBackground: Resveratrol (RSV) has a wide range of diabetic cardioprotective effects. It is currently recognized as a dietary supplement.Aim of Study: To investigate the impact of RSV on the molecular expression pattern of AMP-activated protein kinase (AMPK) and the glycogen synthase kinase-3(3 serine 9 (GSK-3(3S9) in diabetic cardiomyopathy.Methods: We investigated this point using three groups of Wistar albino rats; control group, diabetic cardiomyopathy rats (DCM) and diabetics treated with RSV (DM-RSV) for 20 weeks. Echocardiography was performed at base line, and every 4 weeks. At the end of the study, Ex-vivo assessment of myocardial contractility was performed. The molecular changes in the cardiac tissues were evaluated in all groups for assessment of the silent information regulator (SIRT1), GSK-3(3S9 and the AMPK levels. Histological assessment was done for all cardiac tissues. Apoptosis was assessed by measuring the modulation in the Bax/Bcl2 ratio and poly (ADP-ribose) polymerase-1 (PARP1) levels, trying to explore the RSV underlying mechanism of action.Results: Marked deterioration in the cardiac functions was detected in the diabetic non treated group. The decreased levels of SIRT1, AMPK and GSK-3(3S9 that was associated with increased apoptotic markers, may be the cause of dete-riorated cardiac functions. Assessment of the myocardial functions showed improvement in the diabetic RSV treated group. RSV aimed to normalize the hyperglycemic state and the disturbed molecular pattern associated with diabetes.Conclusion: Prolonged RSV administration protects the diabetic hearts. This could be explained by the interplay between SIRT1, AMPK and the GSK-3(3S9 levels.

Resveratrol ameliorates brain injury via the TGF-β-mediated ERK signaling pathway in a rat model of cerebral hemorrhage.

Brain injury is the most common intracranial injury in human cerebrovascular disease, which may lead to ischemic stroke. Resveratrol induces ameliorative effects in the treatment of certain human diseases by regulating different signaling pathways. The present study assessed the therapeutic effects of resveratrol and its potential mechanism of action in the neurons from rats with ischemia/reperfusion-induced cerebral hemorrhage. The rat model of cerebral hemorrhage was established and reverse transcription-quantitative polymerase chain reaction, western blotting, immunohistochemistry and terminal deoxynucleotidyl-transferase-mediated dUTP nick end labeling assays were subsequently performed to assess the therapeutic effects of resveratrol. The results demonstrated that treatment with resveratrol (10 mg/kg/day) decreased cerebral water content, hippocampal cell apoptosis and cerebral infarct volume compared with the PBS-treated group. Resveratrol treatment also increased neuronal cell viability, improved neurological function and blood brain barrier disruption compared with the PBS group following 21 days of treatment. The administration of resveratrol was demonstrated to decrease the levels of certain inflammatory factors, including ionized calcium binding adaptor molecule 1 and myeloperoxidase, in rats with cerebral hemorrhage. The results revealed that treatment with resveratrol regulated neuronal apoptosis by downregulating the transforming growth factor-β (TGF-β)-mediated extracellular signal-regulated kinase (ERK) signaling pathway. In conclusion, these results indicate that resveratrol decreases ischemia/reperfusion-induced neuronal apoptosis by downregulating the TGF-β-mediated ERK pathway in a rat model of cerebral hemorrhage and may serve as a potential agent for the treatment of cerebral hemorrhage.

Orally administered resveratrol enhances the therapeutic effect of autologous transplanted adipose-derived stem cells on rats with diabetic hepatopathy

ABSTRACTStem cell therapy is a promising treatment for hepatopathy due to diabetes mellitus (DM); oral resveratrol treatment exhibits protective effects. We investigated whether protective effects could be produced in liver of diabetic rats receiving autologous adipose-derived stem cell transplantation (ADSC) plus oral resveratrol administration. Male rats were divided into four groups: sham group; streptozotocin induced DM group; DM + ADSC group, in which DM rats were treated with 106 stem cells/rat; and DM + R + ADSC group, in which DM rats were treated with ADSC and oral resveratrol. The DM group exhibited apoptosis, inflammation and fibrosis, whereas Sirt-1 and survival signaling were suppressed. Pathological conditions other than survival signaling were improved in the DM + ADSC group. All pathological conditions were improved in the DM + R + ADSC group. Also, the oxidative stress level in the blood was reduced in the DM + R + ADSC group compared to the sham group. Oral resveratrol administration appears to reduce oxidative damage and enhances survival signaling in diabetic liver. The therapeutic response in the DM + R + ADSC group was better than in the DM + ADSC group.

Resveratrol prevents chronic intermittent hypoxia-induced cardiac hypertrophy by targeting the PI3K/AKT/mTOR pathway

AimsResveratrol is a polyphenolic compound that has received much attention for its use in ameliorating various systemic pathological conditions. The present study was performed to investigate whether the resveratrol alleviated cardiac hypertrophy and functional remodelling by regulating autophagy. Materials and methodsMale rats were exposed to CIH 8 h/day for five weeks and/or intragastric administration of resveratrol daily. The morphological and echocardiography were used to evaluate the cardiac protective effects. The apoptosis was detected by TUNEL staining. The biochemical assessments were used to evaluate oxidative stress. Further, the effect of resveratrol on autophagy and PI3K/AKT/mTOR pathway was investigated. Key findingsThe CIH group exhibited increased heart weight/body weight and left ventricle weight/body weight ratios, which was accompanied by left ventricular remodelling. Echocardiography analysis showed that CIH-treated rats had significantly higher left ventricular posterior wall thickness, ejection fraction and fractional shortening than those of controls. In addition, the apoptosis index and oxidative markers were significantly elevated in the CIH group versus the control. The autophagy marker Beclin-1 was elevated, while p62 was decreased by CIH treatment. Resveratrol treatment significantly improved cardiac function and alleviated cardiac hypertrophy, oxidative stress, and apoptosis in CIH rats. Further results indicated that PI3K/AKT pathway-mediated inhibition of the mammalian target of rapamycin (mTOR) pathway played a role in the activation of autophagy by resveratrol after CIH stimulation. SignificanceIn conclusion, resveratrol supplementation during CIH upregulates autophagy by targeting the PI3K/AKT/mTOR pathway, which appears to be beneficial for resisting cardiac hypertrophy.

Acute Resveratrol Administration Increases Neural Effort but Not Whole Body Metabolism or Cognitive Performance in Healthy, Young Participants

Research into the cognitive enhancing effects of polyphenols is small but growing. Single doses of the stilbene polyphenol resveratrol can increase cerebral blood flow (CBF) but have failed to improve cognitive performance in young, healthy cohorts. As both CBF and overall energy expenditure are closely related to neural activity, this randomised, double-blind, placebo-controlled, crossover investigation, assessed the metabolic consequences of resveratrol during high cognitive demand via indirect calorimetry (ICa). Twenty-seven, self-reported healthy participants (15 male, 12 female; mean age = 22) who reported themselves free of any food intolerances and any herbal supplementation or prescription medications were recruited for the current study. Participants arrived at the testing facility at 8 a.m. on three separate occasions to complete a serial subtraction demand battery 45 min and 2 and 3 h following administration with 500 mg, 250 mg trans-resveratrol or inert placebo, while connected to an online gas analysis system. A series of within-subjects ANOVAs (with planned comparisons) revealed a significant shift towards higher carbohydrate oxidisation during cognitive demand, as indexed by a significant increase in respiratory exchange ratio (RER) at 45-min and 3-h time points, following administration of 500 mg resveratrol. Despite this, no subsequent resveratrol-related benefits to cognitive performance were observed. These results show that acute supplementation with resveratrol in young, healthy adults can modulate fuel utilization during cognitive demand, yet this does not translate into clear improvements in cognitive performance. This study adds further understanding behind the lack of cognitive effects of resveratrol in young and or healthy individuals. Future research should direct efforts towards assessing the cognitive impact of resveratrol, and other vasoactive polyphenols, in populations with age-related or dietary-induced metabolic deficits.

Therapeutic effects of resveratrol in Escherichia coli-induced rat endometritis model.

Endometritis is an inflammatory disorder of the endometrial lining of the uterine tissue in postpartum stage. Endometritis mostly progresses subclinically and causes infertility through the disruption of the hormonal balance. It has been shown in many studies that resveratrol has anti-inflammatory and antioxidant properties. However, the possible beneficial effects of resveratrol in endometritis have not been determined yet. The aim of the present study is to evaluate the treatment potential of resveratrol in an experimentally induced endometritis model in rats. Endometritis was induced in 12-week-old female, nonpregnant, Sprague Dawley rats. The animals were divided into six groups: control (NaCl 0.9%) and endometritis (NaCl 0.9%), marbofloxacin + PGF2α, marbofloxacin, marbofloxacin + resveratrol, and resveratrol groups. To induce endometritis, 5mg/kg/s.c. progesterone was given for 5days, and then Escherichia coli (50μl, 1 × 105cfu/rat) was injected in the right cornu uteri following laparotomy. Sixteen hours after bacterial inoculation, the treatment protocol was applied for 14days. At the end of the experiment, the total oxidant status (TOS) and total antioxidant status (TAS) were examined spectrophotometrically in uterus tissues. The severity of inflammation in uterus samples and follicular activity in ovarian tissues were histopathologically evaluated. In addition, serum cytokine levels were determined. While TAS in uterine tissue significantly increased in the resveratrol group when compared to that of the other groups (p < 0.05), there was no difference between the groups in TOS (p > 0.05). The inflammation of the endometrium and the numbers of corpus luteum in the endometritis group were highly significant when compared to those of the other groups (p < 0.05). The recovery of inflammation and follicular activity were similar to those of the other groups in resveratrol group. However, it was realized that resveratrol administration reduced serum cytokine levels. According to the results of the current study, resveratrol was found to be effective in the treatment of endometritis with its antioxidant and anti-inflammatory functions.

Sonication-assisted Layer-by-Layer self-assembly nanoparticles for resveratrol delivery.

This paper advances the development of a novel drug nanodelivery solution to the oral administration of resveratrol (RSV), a low soluble drug whose recognized therapeutic applications are circumscribed when administered in the free compound form. Layer-by-Layer (LbL) self-assembly is an emergent nanotechnology proposed to address this concern with means to afford control over key formulation parameters, which are able to ultimately promote an improved pharmacokinetics. LbL self-assembly consists in the sequential adsorption of oppositely charged polyelectrolytes upon a low soluble drug nanoparticle (NP) template, giving rise to onion-like multilayered nanoarchitectures. In this work, RSV nanoprecipitation followed by LbL self-assembly of polyelectrolytes, led by a washless approach, was carried out by using the cationic poly(allylamine hydrochloride) (PAH) and the anionic dextran sulfate (DS) as polyelectrolytes towards the nanoencapsulation of RSV. Each saturated polyelectrolyte layer deposition involved the rigorous polyelectrolyte concentration assessment which was accomplished by tracing titration curves. This way, aqueous RSV nanocores and RSV LbL nanoformulations with a distinct number of PAH/DS bilayers were developed, including 2.5 (RSV-(PAH/DS)2.5 NPs), 5.5 (RSV-(PAH/DS)5.5 NPs) and 7.5 (RSV-(PAH/DS)7.5 NPs) bilayered nanoformulations. Homogenous particle size distributions at the desired nanoscale interval (ca. 116-220 nm; polydispersity index below 0.15), good colloidal (zeta potential magnitudes ca. ± 20-30 mV) and chemical stabilizations, high encapsulation efficiency (above 90%) together with an excellent cytocompatibility with Caco-2 cells (cell viability above 90%) were observed for all the nanoformulations. Eventfully, LbL NPs promoted a controlled release of RSV pursuant to the number of polyelectrolyte bilayers under simulated gastrointestinal conditions, particularly in the intestine medium, emphasizing their biopharmaceutical advantage. Our findings manifestly pinpoint that LbL PAH/DS NPs constitute a promising nanodelivery system for the oral delivery of RSV, providing a rational strategy to enlarge the implementation range of this interesting polyphenol, which is possibly the most actively investigated phytochemical worldwide.

Maternal resveratrol administration protects against gestational diabetes-induced glucose intolerance and islet dysfunction in the rat offspring.

Maternal resveratrol (RESV) administration in gestational diabetes (GDM) restored normoglycaemia and insulin secretion. GDM-induced obesity was prevented in male GDM+RESV offspring but not in females. GDM+RESV offspring exhibited improved glucose tolerance and insulin sensitivity. GDM+RESV restored hepatic glucose homeostasis in offspring. Glucose-stimulated insulin secretion was enhanced in GDM+RESV offspring. Gestational diabetes (GDM), the most common complication of pregnancy, is associated with adverse metabolic health outcomes in offspring. Using a rat model of diet-induced GDM, we investigated whether maternal resveratrol (RESV) supplementation (147mgkg-1 day-1 ) in the third week of pregnancy could improve maternal glycaemia and protect the offspring from developing metabolic dysfunction. Female Sprague-Dawley rats consumed a high-fat and sucrose (HFS) diet to induce GDM. Lean controls consumed a low-fat (LF) diet. In the third trimester, when maternal hyperglycaemia was observed, the HFS diet was supplemented with RESV. At weaning, offspring were randomly assigned a LF or HFS diet until 15weeks of age. In pregnant dams, RESV restored glucose tolerance, normoglycaemia and improved insulin secretion. At 15weeks of age, GDM+RESV-HFS male offspring were less obese than the GDM-HFS offspring. By contrast, the female GDM+RESV-HFS offspring were similarly as obese as the GDM-HFS group. Hepatic steatosis, insulin resistance, glucose intolerance and dysregulated gluconeogenesis were observed in the male GDM offspring and were attenuated in the offspring of GDM+RESV dams. The dysregulation of several metabolic genes (e.g. ppara, lpl, pepck and g6p) in the livers of GDM offspring was attenuated in the GDM+RESV offspring group. Glucose stimulated insulin secretion was also improved in the islets from offspring of GDM+RESV dams. Thus, maternal RESV supplementation during the third trimester of pregnancy and lactation induced several beneficial metabolic health outcomes for both mothers and offspring. Therefore, RESV could be an alternative to current GDM treatments.