Antioxidant Effects Of Resveratrol Research Articles

Antioxidant effects of resveratrol in granulocytes from multiple sclerosis patients

Aim: Neuroinflammation is a characteristic of multiple sclerosis (MS). Resveratrol (RSV) has potent antioxidant properties and has emerged as a promising therapeutic agent for various inflammatory diseases. This study investigated the effects of RSV on inflammatory responses via reactive oxygen species (ROS) production and leukocyte cytokine secretion in patients with MS and healthy controls. Methods: The effects of RSV on ROS production in resting and stimulated granulocytes (in the presence of opsonized particles) were assessed using luminol-dependent chemiluminescence. The cytokines interleukin (IL)-10, IL-1β, IL-6, and high mobility group box 1 (HMGB1) in the supernatant of peripheral blood mononuclear cells (PBMNCs) were quantified using enzyme-linked immunosorbent assay (ELISA). Results: RSV significantly downregulated ROS production in resting and stimulated granulocytes in patients with MS and healthy controls. In the control group, RSV reduced IL-6 levels by 49% in the PBMNC supernatant, whereas IL-6 levels remained unchanged in the MS group. Interestingly, higher levels of IL-10 were detected in PBMNC supernatants from patients with MS than in controls. No significant changes were observed in IL-1β and HMGB1 levels in the PBMNC supernatant. Conclusions: Controlling ROS production is a key target for treating inflammatory diseases. Our findings suggest that RSV can effectively modulate ROS production in MS, highlighting its potential as a promising adjunct therapy for controlling oxidative innate immune responses in MS.

A Study on the Antioxidant Effect of Resveratrol on Milk Thistle Seed Oil at Frying Temperature

A Study on the Antioxidant Effect of Resveratrol on Milk Thistle Seed Oil at Frying Temperature

Protective effects of resveratrol against fumonisin B1-induced liver toxicity in mice.

The aim of this study was to investigate the effects of resveratrol against fumonisin B1 (FB1)-induced liver toxicity, as, to the best of our knowledge, these effects have not been investigated yet, even though the toxic effects and mechanisms of FB1 and the antioxidative effects of resveratrol are well known. 40 BALB/c mice were divided into control, FB1, resveratrol, and FB1+resveratrol groups. Control received saline for 14 days. The FB1 group received 2.25 mg/kg FB1 every other day for 14 days. The resveratrol group received 10 mg/kg resveratrol for 14 days. The FB1+resveratrol group received 2.25 mg/kg FB1 every other day and 10 mg/kg resveratrol every day for 14 days. All administrations were peritoneal. Alanine aminotransferase (ALT), aspartate aminotransferase (AST), total sialic acid (TSA) levels were analysed in serum samples, while total antioxidant status (TAS) and total oxidant status (TOS) were measured in the liver. Additionally, the liver tissue was examined for histopathological changes. AST, ALT, and TSA were significantly higher in the FB1 group than control. Resveratrol countered FB1 effects for all parameters, including TOS and TAS. Liver histology showed FB1-induced hyperaemia, infiltrations, and megalokaryosis in some hepatocytes. No pathological findings were detected in the control, resveratrol, or FB1+resveratrol group. Our findings confirm resveratrol's protective effect against liver damage and oxidative stress caused by FB1. In addition, they suggest that increased serum TSA levels can be used as a biomarker of FB1-induced hepatotoxicity.

Effect of resveratrol on Sn-Fe alloy electrodeposition

• We verified that resveratrol has better antioxidant properties than other stabilizers. • Resveratrol was successfully introduced to bath for improving the stability. • We confirmed the optimal concentration of resveratrol in the bath. The Sn-Fe alloy coating is a potential choice for decorative coatings and electronic products because of its excellent performance. However, oxidation of the bath is likely to occur in the process of use, which limits the production of electrodeposition of Sn-Fe alloy. Resveratrol has excellent antioxidant capacity and is considered as a non-polluting natural antioxidant. However, the understanding of using of resveratrol as stabilizer for electroplating solution in the field of electrodeposition is limited. In this study, resveratrol, hydroquinone and TBHQ are selected as the stabilizers of the electroplating bath to conduct comparative experiments for measuring the stability effect of resveratrol. The antioxidant capacities of three stabilizers are compared by means of the natural oxidation experiment, H 2 O 2 accelerated oxidation experiment and electrochemical testing. The natural oxidation experiment and H 2 O 2 accelerated oxidation experiment confirm that the antioxidant effect of resveratrol is higher than hydroquinone and TBHQ. To determine the optimal concentration of resveratrol in the electroplating solution, EIS and salt spray test were conducted. These results show that appropriate resveratrol can improve the corrosion resistance of the coating, but excessive resveratrol is detrimental to corrosion resistance. Therefore, the optimal concentration of resveratrol in the electroplating solution is 1.0 g/L.

Histomorphological changes and molecular mechanisms underlying the ameliorative effect of resveratrol on the liver of silver nanoparticles-exposed rats

ABSTRACT Exposure to the deleterious effects of silver nanoparticles (AgNPs) is inevitable due to their wide use in medicine and daily life. The current study aimed to delineate the histomorphological changes and the molecular mechanisms underlying the ameliorative effect of Resveratrol (RSV) on rats’ livers exposed to AgNPs. Fifty healthy adult male Wistar albino rats were divided into four groups: control, AgNPs-exposed, RSV-treated after AgNPs exposure, and recovery groups. Liver sections were examined by light and electron microscopes, and immunohistochemistry was performed for detection of activated caspase3 and TNFα. Serum ALT and AST, plasma levels of TNFα, IL-6, GSH and SOD were measured. mRNA expression of SIRT1, ADORA3, PAI, CDK1, Nrf2 and NFκB genes in liver tissue homogenate was performed using qRT-PCR. AgNPs-exposure for 28 days caused marked liver tissue damage with trapping in hepatocytes and Kupffer cells, while RSV treatment ameliorated liver ultrastructure and function. Our results clarified the molecular basis of RSV ameliorative effect on liver tissue by significant upregulation of SIRT1-NrF2 signaling pathway with increased levels of the antioxidant GSH and SOD, which represent the antioxidant effect of RSV. Significant upregulation of the protective ADORA3 with downregulation of the proinflammatory PAI-1 and NFκB mRNA expression levels besides decreased plasma levels of TNFα, IL-6 and decreased immunoexpression of TNFα in liver tissue, represent the anti-inflammatory effect of RSV. In addition, decreased immunoexpression of caspase3 and downregulation of CDK1 expression, represent its antiapoptotic effect. In conclusion: RSV ameliorates AgNPs-induced liver damage by antioxidant, anti-inflammatory and antiapoptotic effects. Abbreviations: AgNPs: Silver nanoparticles, RSV: Resveratrol, ROS: Reactive oxygen species, ESR: Electron spin resonance, DMPO: 5,5-Dimethyl-1-pyrroline-N-oxide, H2O2: Hydrogen peroxide, SOD: Superoxide dismutase, CAT: Catalase, GPx: Glutathione peroxidase, MPTP: Methyl-4-phenyl-1.2.3.6-tetrahydropyridine, MDA: Malondialdehyde, TNF: Tumor necrosis factor, GSH: Glutathione, Nrf2: Nuclear factor-erythroid 2-related factor 2, ARE: Antioxidant response elements, KEAP1: Kelch-1ike ECH-associated protein l, AMPK: AMP-activated protein kinase, HO-1: Heme oxygenase-1, NF-κB: Nuclear factor-kappa B, SIRT1: Sirtuins, FOXO: Forkhead box, UCP2: Uncoupling protein 2, STZ: Streptozotocin nicotinamide, HSC: hepatic stellate cells, ECM: extracellular matrix.

Anti-inflammatory effect of resveratrol attenuates the severity of diabetic neuropathy by activating the Nrf2 pathway.

The mechanisms underlying the development of neuropathy associated with diabetes mellitus are not fully understood. Resveratrol, as a nonflavonoid polyphenol, plays a variety of beneficial roles in the treatment of chronic diseases such as Alzheimer's disease, coronary heart disease and obesity. In our study, the role of nuclear erythroid 2-related factor 2 (Nrf2) in resveratrol-mediated protection against streptozotocin-induced diabetic peripheral neuropathy (DPN) was investigated, and the antioxidant effect of resveratrol in diabetic peripheral nerves was studied. The STZ-treated model mice were divided into two groups. The resveratrol group was intragastrically administered 10 ml/kg 10% resveratrol once a day until the 12th week after STZ injection. The vehicle-treated mice were injected with the same volume of DMSO. Analysis of the effects of resveratrol in DPN revealed the following novel findings: (i) the pain and temperature sensitivities of diabetic mice were improved after treatment with resveratrol; (ii) Nrf2 expression was increased in the diabetic peripheral nerves of resveratrol-treated mice, and NF-KB pathway inhibition protected nerves upon resveratrol treatment in peripheral neuropathy; and (iii) resveratrol modulated the anti-inflammatory microenvironment of peripheral nerves by increasing Nrf2 activation and the expression of p-p65, and these changes may have been responsible for the neuroprotective effect of resveratrol in DPN, which was confirmed by Nrf2 knockout in diabetic mice. Overall, this study demonstrates that resveratrol may attenuate the severity of DPN by protecting peripheral nerves from apoptosis by inhibiting the NF-KB pathway and increasing Nrf2 expression.

Resveratrol prevents inflammation and oxidative stress response in LPS-induced human gingival fibroblasts by targeting the PI3K/AKT and Wnt/β-catenin signaling pathways.

This study aimed to elucidate the anti-inflammatory and antioxidant properties of resveratrol (RSV) in human gingival fibroblasts (HGFs) following stimulation by P. gingivalis lipopolysaccharide (LPS). The levels of the inflammatory cytokines IL-1β, IL-6, IL-8 and TNFα, the activity of the antioxidant enzymes SOD and GSH-Px, and the levels of MDA, were evaluated by ELISA. It was observed that the expression of IL-1β, IL-6, IL-8 and TNFα in LPS-induced HGFs was significantly downregulated by RSV in a dose-dependent manner. RSV also partly increased oxidative stress (OS)-related factors, including SOD and GSH-Px, which was accompanied by a decrease in MDA production, although the results were not statistically significant. Additionally, RSV-induced deactivation of the PI3K/AKT and Wnt/β-catenin pathways in LPS-induced HGFs was observed by western blot analysis. Subsequently, it was demonstrated treatment with PI3K/AKT pathway inhibitor (LY294002) or Wnt/β-catenin pathway inhibitor (Dickkopf-1, DKK-1) could further enhance the anti-inflammatory and antioxidant effects of RSV by downregulating the expression of IL-1β, IL-6, IL-8 and TNFα, and the production of MDA, and increasing the activity of SOD and GSH-Px in LPS-induced HGFs. These results suggested RSV attenuated the inflammation and OS injury of P. gingivalis LPS-treated HGFs by deactivating the PI3K/AKT and Wnt/β-catenin signaling pathways.

Fibrinogen Increases Resveratrol Solubility and Prevents it from Oxidation.

The French paradox describes a lower incidence of cardiovascular problems despite a high intake of saturated fats. This phenomenon was associated with higher consumption of red wine, as it was later discovered that the presence of antioxidants, including resveratrol, have beneficial effects. We hypothesized that resveratrol may have a more direct role in protection from harmful oxidation, presumably through binding to important proteins of the blood coagulation process. Spectrofluorimetry demonstrated that resveratrol is capable of binding to fibrinogen, the main protein in the coagulation process, which is also important as a food additive. Various spectroscopic methods determined that binding does not cause fibrinogen unfolding or destabilization since protein melting temperature remains unchanged. A mutually protective effect against the free radical-induced oxidation of polyphenol and fibrinogen was found. The presence of fibrinogen caused only a negligible masking effect of the antioxidative abilities of resveratrol, measured by a reduction of hexacyanoferrate (III), while greatly increasing its solubility in an aqueous environment, thus increasing its potential bioavailability. Due to its interaction with fibrinogen, resveratrol may serve as an antioxidant at the site of injury. The antioxidative effect of resveratrol may also protect and thus keep the desired characteristics of fibrinogen during the application of this protein as a food additive.

Resveratrol diminishes bisphenol A-induced oxidative stress through TRPM2 channel in the mouse kidney cortical collecting duct cells

Bisphenol A (BisPH-A) is a latent danger that threatens our health, which we frequently exposure in our modern life (e.g. the widespread use of drinking water in plastic pet bottles). But the BisPH-A induced transient receptor potential melastatin 2 (TRPM2)-mediated oxidative stress and apoptosis in these cells has not been studied yet. Calcium (Ca2+) plays an important role in a versatile intracellular signal transduction that works over a wide range to regulate oxidative stress processes. TRPM2 is activated by oxidative stress and it has emerged as an important Ca2+ signaling mechanism in a variety of cells, contributing many cellular functions including cell death. Resveratrol (RESV), which belongs to the polyphenol group, acts as an antioxidant, eliminating cellular oxidative stress and increasing the body’s resistance to diseases. The current study aimed to elucidate the effect of antioxidant resveratrol on TRPM2-mediated oxidative stress induced by BisPH-A exposure in the mouse kidney cortical collecting duct cells (mpkCCDcl4). The cells were divided into four groups as control, resveratrol (50 µM for 24 h), BisPH-A (100 µM for 24 h) and BisPH-A + RESV. Intracellular free Ca2+ concentrations and TRPM2 channel currents were high in BisPH-A treated cells, but decreased with resveratrol treatment. In addition, BisPH-A induced mitochondrial membrane depolarization, reactive oxygen species (ROS), caspase 3, caspase 9 and apoptosis values were decreased by the resveratrol treatment. In conclusion, resveratrol protected cells from BisPH-A induced oxidative damage. In this study, we showed that TRPM2 channel mediates this protective effect of resveratrol.

Carbon Monoxide Partially Mediates Protective Effect of Resveratrol Against UVB-Induced Oxidative Stress in Human Keratinocytes.

Based on the antioxidative effect of resveratrol (RES) in mitigating reactive oxygen species (ROS) production through the induction of nuclear factor-erythroid 2-related factor-2 (Nrf2)/heme oxigenase-1 (HO-1) signaling pathway, we investigated whether the protective activity of RES against ROS-mediated cytotoxicity is mediated by intracellular carbon monoxide (CO), a product of HO-1 activity, in ultraviolet B (UVB)-irradiated human keratinocyte HaCaT cells. The cells were exposed to UVB radiation following treatment with RES and/or CO-releasing molecule-2 (CORM-2). RES and/or CORM-2 upregulated HO-1 protein expression, accompanied by a gradual reduction of UVB-induced intracellular ROS levels. CORM-2 reduced intracellular ROS in the presence of tin protoporphyrin IX, an HO-1 inhibitor, indicating that the cytoprotection observed was mediated by intracellular CO and not by HO-1 itself. Moreover, CORM-2 decreased RES-stimulated mitochondrial quantity and respiration and increased the cytosolic protein expressions of radical-scavenging superoxide dismutases, SOD1 and SOD2. Taken together, our observations suggest that RES and intracellular CO act independently, at least partly, in attenuating cellular oxidative stress by promoting antioxidant enzyme expressions and inhibiting mitochondrial respiration in UVB-exposed keratinocytes.

Neurological recovery and antioxidant effects of resveratrol in rats with spinal cord injury: a meta-analysis

Objective:To critically assess the neurological recovery and antioxidant effects of resveratrol in rat models of spinal cord injury.Data sources:Using “spinal cord injury”, “resveratrol” and “animal experiment” as the main search terms, all studies on the treatment of spinal cord injury in rats by resveratrol were searched for in PubMed, EMBASE, MEDLINE, Web of Science, Science Direct, China National Knowledge Infrastructure, Wanfang, VIP, and SinoMed databases by computer. The search was conducted from their inception date to April 2017. No language restriction was used in the literature search.Data selection:The methodological quality of each study was assessed by the initial Stroke Therapy Academic Industry Roundtable recommendations. Two reviewers independently selected studies according to the title, abstract and full text. The risk of bias in the included studies was also evaluated. Meta-analyses were performed with Review Manager 5.3 software.Outcome measures:Neurological function was assessed by the Basso, Beattie, and Bresnahan scale score, inclined plane score and Gale’s motor function score. Molecular-biological analysis of antioxidative effects was conducted to determine superoxide dismutase levels, malondialdehyde levels, nitric oxide synthase activity, nitric oxide levels, xanthine oxidase and glutathione levels in spinal cord tissues.Results:The methodological quality of the 12 included studies was poor. The results of meta-analysis showed that compared with the control group, resveratrol significantly increased the Basso, Beattie, and Bresnahan scale scores after spinal cord injury (n = 300, mean difference (MD) = 3.85, 95% confidence interval (CI) [2.10, 5.59], P < 0.0001). Compared with the control group, superoxide dismutase levels were significantly elevated (n = 138, standardized mean difference (SMD) = 5.22, 95% CI [2.98, 7.45], P < 0.00001), but malondialdehyde levels were significantly diminished (n = 84, SMD = –3.64, 95% CI [–5.84, –1.43], P = 0.001) in the spinal cord of the resveratrol treatment group.Conclusions:Resveratrol promoted neurological recovery and exerted antioxidative effects in rat models of spinal cord injury. The limited quality of the included studies reduces the application of this meta-analysis. Therefore, more high-quality studies are needed to provide more rigorous and objective evidence for the pre-clinical treatment of spinal cord injury.

Abstract P2005: Antioxidant Resveratrol Attenuates Cardiac Fibrosis and Reduces Matrix Metalloproteinase-2 Activity in Heart Failure Rats

Increased reactive oxygen species activate matrix metalloproteinases (MMP) playing a critical role in cardiovascular remodeling after myocardial infarction (MI). We evaluated the antioxidant effect of resveratrol (RESV) on cardiac remodeling and MMP-2 activity in heart failure (HF) rats. Wistar rats were divided into the following groups: Control; Control+RESV; HF; HF+RESV (10mg/kg/day, p.o., 4 wk). The MI was elicited by ligation of the coronary artery. After four weeks, the animals were anesthetized to evaluate the cardiac function and to collect the hearts and blood samples. Heart weight/body weight (HW/BW, mg/g) ratio and the infarct size were calculated. Histological assessment of the left ventricle was carried out with hematoxylin/eosin, and fibrosis was quantified with Masson trichrome-staining. Cardiac and plasma MMP-2 activities were determined by gel zymography. The oxidative stress was assessed measuring the thiobarbituric acid reactive substances (TBARS) from plasma. HF and HF+RESV showed similar infarct size. The HW/BW ratio increased (3.7±0.2 vs 3.8±0.2 vs 3.0±0.05). RESV improved the maximal slope of the systolic increment of left ventricular pressure in HF animals (9004±1120 vs 5849±595 vs 7181±533 mmHg/s) and reduced the end diastolic pressure (4±1 vs 18±4 vs 7±1 mmHg). HF increased TBARS, whereas RESV produced an antioxidant effect in HF+RESV group (11.2±0.9 vs 21.7±3 vs 8.2±1.4 μmol/L). HF augmented cardiac fibrosis (30,8±1,3 vs 8,8±0,5%) and myocyte hypertrophy (12,2±0,7 vs 8,8±0,3μm). RESV reduced collagen deposition in HF hearts (22,7±1,9%), but did not reduce the myocyte hypertrophy (11,7±0,6 μm). Cardiac and plasma MMP-2 activity were higher in HF animals (plasma: 1344±39 vs. 1164±47; heart: 536±54 vs. 262±18). RESV decreased plasma MMP-2 activity in control (992±27) and HF animals (1200±49) and reduced cardiac MMP-2 activity only in HF+RESV group (426±42). In conclusion, the antioxidant effect of RESV improved cardiac function and fibrosis and reduced MMP-2 levels in the heart and plasma from HF rats.

Resveratrol protects UVB‐irradiated keratinocytes by upregulating HO‐1 expression and improving mitochondrial function via endogenous CO signaling

Excessive exposure to ultraviolet (UV) radiation has been reported to promote uncontrolled reactive oxygen species (ROS) production, particularly in the mitochondria, and thus implicated in the prevalence of skin injuries. Considering the antioxidative effect of resveratrol (RES) in reducing UV‐induced ROS production in human keratinocytes (HaCaT cells) and the role of carbon monoxide (CO) in regulating oxidative stress, we hypothesized that RES may promote cellular antioxidant response by activating heme oxygenase‐1 (HO‐1) which can generate its enzymatic product, CO, in UVB‐irradiated keratinocytes. To test our hypothesis, we treated HaCaT cells with CO‐releasing molecule 2 (CORM‐2) (source of CO) and RES either independently or in combination and irradiated the cells with UVB. Co‐treatment of CO with RES upregulated HO‐1 expression and subsequently reduced intracellular ROS in response to UV irradiation. Moreover, UVB treatment alone induced mitochondrial biogenesis, but treatment with CO and RES did not increase it further. With UVB treatment, RES showed enhanced mitochondrial respiration while CO did not instigate any effect; however, independent or co‐treatment mitigated mitochondrial ROS production. Taken together, our data support the impression that endogenous CO generated from RES‐mediated activation of HO‐1 may play a crucial role in cellular antioxidant response and mitochondrial function.Support or Funding InformationThis work was supported by the Korea Institute of Planning and Evaluation for Technology in Food, Agriculture, Forestry, and Fisheries (IPET) through the High Value‐Added Food Technology Development Program, funded by the Ministry of Agriculture, Food, and Rural Affairs (Grant No. 116026‐03‐2‐HD020), Republic of Korea.This abstract is from the Experimental Biology 2019 Meeting. There is no full text article associated with this abstract published in The FASEB Journal.

Antioxidant effect of resveratrol in single red blood cells measured by thermal fluctuation spectroscopy

The human red blood cell (RBC) membrane has significant elastic capabilities which can be described measuring typical membrane edge fluctuations and mechanical properties by optical techniques. The RBC elastic properties can be affected by changes in the surrounding media. In an attempt to elucidate the molecular mechanisms of the interaction of resveratrol with the red cell membrane and of its antioxidant capacity the changes in mechanical properties of the RBC membrane were analyzed. These studies were carried out through measurements of RBC membrane fluctuations in the presence of the oxidant agent HClO using thermal fluctuation spectroscopy (TFS). The observed results showed that the elastic capabilities of RBC changed with low concentration of hypochlorous acid but without morphological changes. However, in the presence of resveratrol the deformation and decrease of elastic capabilities induced by HClO on RBC decreased. These in vitro results demonstrated the protective effect of RV against the detrimental effects triggered by HClO upon human erythrocytes.

Beneficial Effects of Resveratrol Administration-Focus on Potential Biochemical Mechanisms in Cardiovascular Conditions.

Resveratrol (RV) is a natural non-flavonoid polyphenol and phytoalexin produced by a number of plants such as peanuts, grapes, red wine and berries. Numerous in vitro studies have shown promising results of resveratrol usage as antioxidant, antiplatelet or anti-inflammatory agent. Beneficial effects of resveratrol activity probably result from its ability to purify the body from ROS (reactive oxygen species), inhibition of COX (cyclooxygenase) and activation of many anti-inflammatory pathways. Administration of the polyphenol has a potential to slow down the development of CVD (cardiovascular disease) by influencing on certain risk factors such as development of diabetes or atherosclerosis. Resveratrol induced an increase in Sirtuin-1 level, which by disrupting the TLR4/NF-κB/STAT signal cascade (toll-like receptor 4/nuclear factor κ-light-chain enhancer of activated B cells/signal transducer and activator of transcription) reduces production of cytokines in activated microglia. Resveratrol caused an attenuation of macrophage/mast cell-derived pro-inflammatory factors such as PAF (platelet-activating factor), TNF-α (tumour necrosis factor-α and histamine. Endothelial and anti-oxidative effect of resveratrol may contribute to better outcomes in stroke management. By increasing BDNF (brain-derived neurotrophic factor) serum concentration and inducing NOS-3 (nitric oxide synthase-3) activity resveratrol may have possible therapeutical effects on cognitive impairments and dementias especially in those characterized by defective cerebrovascular blood flow.

Systematic review and meta-analysis of the protective effect of resveratrol on multiple organ injury induced by sepsis in animal models.

Sepsis may directly lead to multiple organ failure, which is among the leading causes of mortality in critically ill patients. According to data released by the Global Sepsis Alliance, the number of mortalities due to sepsis exceeded the combined number for prostate cancer, breast cancer and AIDS in 2012. To date, studies have reported that resveratrol has marked positive effects including anti-inflammatory, anti-oxidative and pro-microcirculatory functions in sepsis-induced organ injury, significantly improving the survival time and mortality of sepsis animals. The present systematic review sought to further clarify the efficacy and safety of resveratrol in the treatment of sepsis. Studies on resveratrol application in the treatment of sepsis-induced organ injury in animal models were reviewed by searching various Chinese and other language databases (PubMed, Embase, CNKI, WanFang and WeiPu) and by manually searching the references of related articles. The selection and evaluation of the studies was performed by two independent reviewers. A total of 260 related studies were initially identified. Following application of the exclusion factors and inclusion criteria, 11 studies were included. Meta-analysis revealed that resveratrol exerted significant protective effect in sepsis-induced animal models of organ injury, through anti-inflammatory, anti-oxidant and pro-microcirculatory functions compared with in the placebo group. While nuclear factor κB (NF-κB) and nuclear factor E2-related factor 2 (NRF-2) are the two major signaling pathways to have been associated with the anti-inflammatory and anti-oxidative effects of resveratrol, these factors were not quantified for mean values, therefore not suitable for systematic evaluation. For related factors, the results of meta-analysis were as follows: For tumor necrosis factor-α (TNF-α), the standardized mean difference (SMD) was -13.50 [95% confidence interval (CI): -22.08, -4.91; P=0.002]; for malondialdehyde (MDA), the SMD was -3.10 (95% CI: -5.27, -0.93; P=0.005); for mean arterial pressure the SMD was 1.34 (95% CI: 0.07, 2.62; P=0.04); for interleukin (IL)-6 the SMD was -9.57 (95% CI: -20.90, 1.75; P=0.10); and for IL-10 the SMD was 0.80 (95% CI: -0.73, 2.34; P=0.31). It was concluded that resveratrol exerted significant anti-inflammatory and anti-oxidative effects through NF-κB and NRF-2 signaling pathways in animal models of sepsis-induced multiple organ injury, manifesting as significant downregulation of TNF-α and MDA expression and improved microcirculation, therefore ameliorating septic damage to the body, which may ultimately improve survival ratios.

P-354 - Resveratrol and resveratryl triacetate attenuate inflammatory responses and reactive oxygen species in human epidermal keratinocytes exposed to particulate matter PM10

Airborne particulate matter causes oxidative damage, inflammation, and premature skin aging. The purpose of this study was to examine the anti-inflammatory and anti-oxidative effects of resveratrol and resveratryl triacetate (RTA) against particulate matter PM10. Primary human epidermal keratinocytes were exposed in vitro to PM10 in the absence or presence of resveratrol and RTA. Assays were performed to determine cell viability, production of reactive oxygen species (ROS), and expression of pro-inflammatory cytokines. PM10 treatment (3~100 g mL−1) decreased cell viability and increased ROS production and the expression of pro-inflammatory cytokines, such as tumor necrosis factor-α (TNF-α), interleukin-1f3 (IL-1f3), interleukin-6 (IL-6) and interleukin-8 (IL-8). Resveratrol and RTA at 1~10 M reduced cytotoxicity and ROS production due to PM10. Also, the PM10-induced expression of pro-inflammatory cytokines was attenuated by resveratrol and RTA. This study suggests that resveratrol and RTA can rescue keratinocyte viability and attenuate the inflammatory responses of these cells due to airborne particles.

Effects of combined treatment with ochratoxin A and citrinin on oxidative damage in kidneys and liver of rats

A multimycotoxin analysis approach in grains results in frequent simultaneous findings of nephrotoxic mycotoxins ochratoxin A (OTA) and citrinin (CTN). The mechanism of CTN and OTA toxicities in biological systems is not fully understood but it is known that oxidative stress is involved. In this study, oxidative damage of DNA, lipids, and the concentration of glutathione (GSH), as well as possible antioxidative effects of resveratrol (RSV) were studied in vivo. Male adult Wistar rats were treated orally with OTA (0.125 and 0.250 mg kg−1 b.w.), RSV (20 mg kg−1 b.w.) for 21 days, CTN (20 mg kg−1 b.w.) for two days or with their combinations. The hOGG1 modified comet assay revealed kidneys and liver oxidative DNA damage in OTA + CTN treated animals, which was not reversed by RSV. CTN did not reduce glutathione (GSH) or increase malondialdehyde (MDA) concentration in any tissue, while OTA reduced kidneys GSH and increased kidneys and liver MDA. RSV increased GSH concentrations in all tissues and decreased MDA concentration in the liver only. Oxidative stress is involved in the toxicity of OTA and CTN but it seems that it differs significantly in organs. Most of the effects on GSH and MDA in combined toxicity may be attributed to the toxic effects of OTA. RSV was effective in restoring the depleted GSH in all tissues but had no effect on the MDA concentration and DNA damage.

The role of resveratrol on full – Thickness uterine wound healing in rats

ObjectiveHealing of the uterus after cesarean section and myomectomy operation is clinically important. In this study, we aimed to investigate the effects of resveratrol (3,5,4′-o-trihydroxystilbene) on the wound healing process of the uterus in rats treated with resveratrol following full thickness injury of the uterus. Materials and methodsTwenty-one female wistar albino rats were divided randomly into three groups (1) control group with no intervention (2) injury group with uterine full thickness injury (3) resveratrol group with uterine full thickness injury and treated with resveratrol. Resveratrol was injected by oral gavage at the doses of 0.5 mg/kg/day for 30 days following uterine full thickness injury. Vascular endothelial growth factor (VEGF) and platelet-derived growth factor (PDGF) distributions were assessed using the immunohistochemical methods in tissue and ELISA methods in the tissue homogenate. Glutathione peroxidase (GPx) and superoxide dismutase (SOD) activities were evaluated with colorimetric method and malondialdehyde (MDA) levels also were measured using high performance liquid chromatography in the tissue homogenate. The effects of resveratrol on the uterine histology also were evaluated histologically with the light microscopy. ResultsHistological evaluation and immunohistochemical evaluations showed that treatment with a resveratrol significantly increased the thickness of the uterine wall and VEGF expression and decreased expression PDGF during wound healing. Biochemically, GPx and SOD activities were increased significantly after treatment with resveratrol. Additionally, resveratrol administration decreased MDA levels. ConclusionThese results showed that the antioxidant effects of resveratrol has been shown to have a positive influence on wound healing of the uterus.

Protective Effects of Resveratrol in a Rat Model of Ischemia-Reperfusion Injury of Sciatic Nerve

Objective: The aim of this study was to determine the effects of resveratrol on ischemia- reperfusion (I/R) injury in the rats sciatic nerve. Methods: We used 18 Wistar rats anesthetized with ketamine (50 mg/kg-im). In the sham group, we only performed the surgery and not administer any medication. In the ischemia group, we generated I/R injury in 5 minute intervals with medical treatment of saline only. In the resveratrol group, we brought about the same I/R injury but gave resveratrol before the surgery by per oral. After sacrifice, we studied blood and nerve tissue samples. We evaluated the damage with malondialdehyde (MDA), nitric oxide (NO), and total antioxidant capacity (TAC), both in tissue and blood. Results: Evaluation of serum levels of antioxidant markers and tissue samples demonstrated statistically significant effects of resveratrol in ischemia-reperfusion injury. Conclusion: This study revealed the antioxidant effect of resveratrol as an inhibitor of lipid peroxidation.