Oxidative Medicine and Cellular Longevity

Infundibulicybe geotropa (Bull.) Harmaja is an edible mushroom found in Bolu province in northwestern Turkey. The chemical composition and bioactivity of these mushrooms has not been previously investigated. We examined the phenolic composition, elemental content, and antioxidant and antigenotoxic effects of methanol extracts of fruiting bodies. The phenolic compounds in the fungal samples were determined using high-performance liquid chromatography (HPLC), and element content was determined using atomic absorption spectrophotometry. Total antioxidant status (TAS), total oxidant status (TOS), and oxidative stress index (OSI) were determined using the commercially available Rel assay kit. The antigenotoxic effects of the extract were determined using the MTT assay to assess cell viability and the alkaline single-cell gel electrophoresis assay (Comet assay). The total phenolic content (ppm) of I. geotropa was found to be catechin (), clorogenic acid (), and coumaric acid (). The TAS, TOS, and OSI of the extract were  mmol/L,  μmol/L, and , respectively. The elemental levels were within “normal” range. In HT22 mouse hippocampal neuronal cells, the extract (100 and 200 μg/ml) showed no genotoxic potential and ameliorated hydrogen peroxide- (H₂O₂-) induced oxidative DNA damage. I. geotropa may be considered a good nutrient due to its phenolic constituents and antioxidant potential.

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Objective. In renal ischemia/reperfusion injury (RIRI), nuclear factor κB (NF-κB) initiates the expression of multiple genes involved in inflammatory disease. Inhibition of NF-κB-mediated inducible nitric oxide synthase (iNOS) expression can ameliorate RIRI. Vagus nerve stimulation (VNS) protects against various organs I/R injury. The present study was designed to elucidate the protective effect of VNS on RIRI and its influence on iNOS protein expression. Methods. Eighteen male Sprague-Dawley rats were randomly allocated into the sham group, the I/R group, and the VNS+I/R group, 6 rats per group. An RIRI model was induced by a right nephrectomy and blockade of the left renal pedicle vessels for 45 min. After 6 h of reperfusion, the blood samples and renal samples were collected. The VNS treatment was performed throughout the I/R process in the VNS+I/R group using specific parameters (20 Hz, 0.1 ms in duration, square waves) known to produce a small but reliable bradycardia. Blood was used for evaluation of renal function and inflammatory state. Renal injury was evaluated via TUNEL staining. Renal samples were harvested to evaluate renal oxidative stress, NF-κB p65 levels, and iNOS protein expression. Results. The VNS treatment reduces serum creatinine (Cr) and blood urea nitrogen (BUN) levels. Simultaneously, the levels of tumor necrosis factor alpha (TNF-α), interleukin 6 (IL-6), and interleukin 1-beta (IL-1β) were significantly increased in the I/R group, but VNS treatment markedly ameliorated this inflammatory response. Furthermore, the VNS ameliorated oxidant stress and renal injury, indicated by a decrease in 3-nitrotyrosine (3-NT) formation and MDA and MPO levels and an increase in the SOD level compared to that in the I/R group. Finally, the VNS also significantly decreases NF-κB p65, iNOS, and nitrite/nitrate levels compared to that in the I/R group. Conclusion. Our findings indicate that NF-κB activation increased iNOS expression and promoted RIRI and that VNS treatment attenuated RIRI by inhibiting iNOS expression, oxidative stress, and inflammation via NF-κB inactivation.

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Various lines of evidence suggest that neonatal exposure to general anesthetics, especially repeatedly, results in neuropathological brain changes and long-term cognitive impairment. Although progress has been made in experimental models, the exact mechanism of GA-induced neurotoxicity in the developing brain remains to be clarified. Sirtuin 1 (SIRT1) plays an important role in synaptic plasticity and cognitive performance, and its abnormal reduction is associated with cognitive dysfunction in neurodegenerative diseases. However, the role of SIRT1 in GA-induced neurotoxicity is unclear to date. In this study, we found that the protein level of SIRT1 was inhibited in the hippocampi of developing mice exposed to sevoflurane. Furthermore, the SIRT1 inhibition in hippocampi was associated with brain-derived neurotrophic factor (BDNF) downregulation modulated by methyl-cytosine-phosphate-guanine–binding protein 2 (MeCP2) and cAMP response element-binding protein (CREB). Pretreatment of neonatal mice with resveratrol nearly reversed the reduction in hippocampal SIRT1 expression, which increased the expression of BDNF in developing mice exposed to sevoflurane. Moreover, changes in the levels of CREB and MeCP2, which were considered to interact with BDNF promoter IV, were also rescued by resveratrol. Furthermore, resveratrol improved the cognitive performance in the Morris water maze test of the adult mice with exposure to sevoflurane in the neonatal stage, without changing motor function in the open field test. Taken together, our findings suggested that SIRT1 deficiency regulated BDNF signaling via regulation of the epigenetic activity of MeCP2 and CREB, and resveratrol might be a promising agent for mitigating sevoflurane-induced neurotoxicity in developing mice.

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Catharanthus roseus (C. roseus) and ursolic acid (UA) are ayurvedic medicines with multiple pharmacological activities including antidiabetic activity, but till date, no study is available on their combination. This study documented the antidiabetic efficacy of the combination of C. roseus and UA in rats. Rats were divided into six groups. All groups were given a single dose of Streptozotocin (STZ) at a dose of 50 mg/kg by intraperitoneal route for induction of diabetes, except the normal control group. Group 1 was treated as a normal control (NC) group and fed with saline water, Group 2 as a Diabetes Control group, Group 3 as a STZ+C. roseus ethanolic extract (CREE) group at 50 mg/kg p.o., Group 4 as a STZ+UA group orally at 50 mg/kg, Group 5 as a STZ+CREE (25 mg/kg p.o.)+UA (25 mg/kg p.o.) group, and Group 6 as a STZ+Glimepiride (0.1 mg/kg) group. Diabetes was confirmed after 72 hours by estimation of blood glucose level, and then treatment was given for the next 28 days. During the course of treatment, plasma insulin and blood glucose were measured regularly at the interval of 7 days. At the end of the protocol, blood was collected and animals were sacrificed. The glucose level, insulin level, liver glycogen storage level, and antioxidant enzymes (LPO, CAT, SOD, GPx, GST) were measured. The blood glucose level in Group 5 significantly () reduced to  mg/dl in comparison with that in Group 2 ( mg/dl). The level of plasma insulin in Group 5 increased ( μU/ml) significantly () as compared with that in Group 2 ( μU/ml). In Group 5, the level of glycogen in liver was significantly () increased as compared with that in Group 2 rats. The level of antioxidant enzymes in Group 5 restored toward normal values significantly (; ) as compared with that in Group 2 animals. These findings suggest that low-dose combination of CREE and UA is effective in the treatment of diabetes.

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Elderly population is in high risk of carotid atherosclerosis and artery stenosis (CAS). It has been proved that PON1 polymorphism is associated with low-density lipoprotein (LDL) oxidation, which plays an important role in artery atherosclerosis. CAS is an important cause of ischemic stroke. This study is aimed at investigating the association of PON1 (rs662) polymorphism with the risk of CAS among elderly Chinese population. Consecutive elderly patients with CAS were enrolled into the study. Genotyping for PON1 (rs662) polymorphism was performed on all participants. There were 310 CAS patients in this study, with 88 symptomatic CAS and 222 asymptomatic CAS. G allele had a frequency of 59.66% in symptomatic CAS (sCAS); and A allele had an incidence of 36.93% in asymptomatic CAS (aCAS) (). In all CAS patients with and without symptom, no associations were found in any genotype comparison. However, among aCAS subjects, based on GA phenotype, the odds ratio (OR) of the mutant GG with stenosis severity was 0.20 (). The OR of GG+GA mutation was 0.28 for moderate/severe severity, compared with GA type (). This study indicates that PON1 (rs662) polymorphism is not associated with the presence of symptom among CAS patients. Moreover, PON1 (rs662) polymorphism correlates with stenosis severity among aCAS.

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Almost all human diseases are strongly associated with inflammation, and a deep understanding of the exact mechanism is helpful for treatment. The NLRP3 inflammasome composed of the NLRP3 protein, procaspase-1, and ASC plays a vital role in regulating inflammation. In this review, NLRP3 regulation and activation, its proinflammatory role in inflammatory diseases, interactions with autophagy, and targeted therapeutic approaches in inflammatory diseases will be summarized.

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