scholarly journals Interplay between Intravitreal RvD1 and Local Endogenous Sirtuin-1 in the Protection from Endotoxin-Induced Uveitis in Rats

2015 ◽  
Vol 2015 ◽  
pp. 1-10 ◽  
Author(s):  
S. Rossi ◽  
C. Di Filippo ◽  
C. Gesualdo ◽  
F. Testa ◽  
M. C. Trotta ◽  
...  

Rat endotoxin-induced uveitis (EIU) is a well-established model of human uveitis. In this model, intravitreal injection of resolvin D1 (RvD1, 10–100–1000 ng/kg) 1 hour after subcutaneous treatment of Sprague-Dawley rats with lipopolysaccharide (LPS, 200 μg/rat) significantly prevented the development of uveitis into the eye. RvD1 dose-dependently increased the expression of sirtuin-1 (SIRT1) within the eye, while it decreased the expression of acetyl-p53 and acetyl-FOXO1. These effects were accompanied by local downregulation of some microRNAs related to the expression and activity of SIRT1. These were miR-195-5p, miR-200a-3p, miR-34a-5p, and miR-145-5p. An increase of manganese superoxide dismutase and decrease of caspase 3 were evident after RvD1 treatment. In another set of experiments, the protective effects of RvD1 (1000 ng/kg) were partly abolished by the pretreatment of the rats with EX527 (10 mg/kg/day, i.p.), a specific inhibitor of SIRT1 activity, for 7 days prior to the induction of EIU in rats. Similarly, the effects of RvD1 (1000 ng/kg) on the SIRT1 protein expression were abolished by Boc2,N-t-butoxycarbonyl-PLPLP, a specific formyl-peptide receptor type 2/lipoxin A receptor antagonist. Therefore, an interplay of the SIRT1 activity on the RvD1 mediated resolution of EIU is argued.

2015 ◽  
Vol 2015 ◽  
pp. 1-9 ◽  
Author(s):  
Catherine Crinigan ◽  
Matthew Calhoun ◽  
Karen L. Sweazea

Chronic high fat feeding is correlated with diabetes and kidney disease. However, the impact of short-term high fat diets (HFD) is not well-understood. Six weeks of HFD result in indices of metabolic syndrome (increased adiposity, hyperglycemia, hyperinsulinemia, hyperlipidemia, hyperleptinemia, and impaired endothelium-dependent vasodilation) compared to rats fed on standard chow. The hypothesis was that short-term HFD would induce early signs of renal disease. Young male Sprague-Dawley rats were fed either HFD (60% fat) or standard chow (5% fat) for six weeks. Morphology was determined by measuring changes in renal mass and microstructure. Kidney function was measured by analyzing urinary protein, creatinine, and hydrogen peroxide (H2O2) concentrations, as well as plasma cystatin C concentrations. Renal damage was measured through assessment of urinary oxDNA/RNA concentrations as well as renal lipid peroxidation, tumor necrosis factor alpha (TNFα), and interleukin 6 (IL-6). Despite HFD significantly increasing adiposity and renal mass, there was no evidence of early stage kidney disease as measured by changes in urinary and plasma biomarkers as well as histology. These findings suggest that moderate hyperglycemia and inflammation produced by short-term HFD are not sufficient to damage kidneys or that the ketogenic HFD may have protective effects within the kidneys.


2015 ◽  
Vol 93 (8) ◽  
pp. 625-631 ◽  
Author(s):  
Yan Hu ◽  
Ning Zhang ◽  
Qing Fan ◽  
Musen Lin ◽  
Ce Zhang ◽  
...  

Carnosic acid (CA), found in rosemary, has been reported to have antioxidant and antiadipogenic properties. Here, we investigate the molecular mechanism by which CA inhibits hydrogen peroxide (H2O2)-induced injury in HepG2 cells. Cells were pretreated with 2.5–10 μmol/L CA for 2 h and then exposed to 3 mmol/L H2O2 for an additional 4 h. CA dose-dependently increased cell viability and decreased lactate dehydrogenase activities. Pretreatment with CA completely attenuated the inhibited expression of manganese superoxide dismutase (MnSOD) and the B-cell lymphoma-extra large (Bcl-xL), and reduced glutathione activity caused by H2O2, whereas it reversed reactive oxygen species accumulation and the increase in cleaved caspase-3. Importantly, sirtuin 1 (SIRT1), a NAD+-dependent deacetylase, was significantly increased by CA. Considering the above results, we hypothesized that SIRT1 may play important roles in the protective effects of CA in injury induced by H2O2. As expected, SIRT1 suppression by Ex527 (6-chloro-2,3,4,9-tetrahydro-1H-carbazole-1-carboxamide) and siRNA-mediated SIRT1 silencing (si-SIRT1) significantly aggravated the H2O2-induced increased level of cleaved caspase-3 but greatly reduced the decreased expression of MnSOD and Bcl-xL. Furthermore, the positive regulatory effect of CA was inhibited by si-SIRT1. Collectively, the present study indicated that CA can alleviate H2O2-induced hepatocyte damage through the SIRT1 pathway.


2001 ◽  
Vol 91 (4) ◽  
pp. 1828-1835 ◽  
Author(s):  
Nicole Stupka ◽  
Peter M. Tiidus

The effects of estrogen and ovariectomy on indexes of muscle damage after 2 h of complete hindlimb ischemia and 2 h of reperfusion were investigated in female Sprague-Dawley rats. The rats were assigned to one of three experimental groups: ovariectomized with a 17β-estradiol pellet implant (OE), ovariectomized with a placebo pellet implant (OP), or control with intact ovaries (R). It was hypothesized that following ischemia-reperfusion (I/R), muscle damage indexes [serum creatine kinase (CK) activity, calpain-like activity, inflammatory cell infiltration, and markers of lipid peroxidation (thiobarbituric-reactive substances)] would be lower in the OE and R rats compared with the OP rats due to the protective effects of estrogen. Serum CK activity following I/R was greater ( P < 0.01) in the R rats vs. OP rats and similar in the OP and OE rats. Calpain-like activity was greatest in the R rats ( P < 0.01) and similar in the OP and OE rats. Neutrophil infiltration was assessed using the myeloperoxidase (MPO) assay and immunohistochemical staining for CD43-positive (CD43+) cells. MPO activity was lower ( P < 0.05) in the OE rats compared with any other group and similar in the OP and R rats. The number of CD43+ cells was greater ( P < 0.01) in the OP rats compared with the OE and R rats and similar in the OE and R rats. The OE rats had lower ( P < 0.05) thiobarbituric-reactive substance content following I/R compared with the R and OP rats. Indexes of muscle damage were consistently attenuated in the OE rats but not in the R rats. A 10-fold difference in serum estrogen content may mediate this. Surprisingly, serum CK activity and muscle calpain-like activity were lower ( P< 0.05) in the OP rats compared with the R rats. Increases in serum insulin-like growth factor-1 content ( P < 0.05) due to ovariectomy were hypothesized to account for this finding. Thus both ovariectomy and estrogen supplementation have differential effects on indexes of I/R muscle damage.


2018 ◽  
Vol 9 (1) ◽  
pp. 31-40 ◽  
Author(s):  
Jing Shi ◽  
Guofeng Wu ◽  
Xiaohua Zou ◽  
Ke Jiang

Background/Aims: Cardiac surgery-associated acute kidney injury (CSA-AKI) is one of the most common postoperative complications in intensive care medicine. Baicalin has been shown to have anti-inflammatory and antioxidant roles in various disorders. We aimed to test the protective effects of baicalin on CSA-AKI using a rat model. Methods: Sprague-Dawley rats underwent 75 min of cardiopulmonary bypass (CPB) with 45 min of cardioplegic arrest (CA) to establish the AKI model. Baicalin was administered at different doses intragastrically 1 h before CPB. The control and treated rats were subjected to the evaluation of different kidney injury index and inflammation biomarkers. Results: Baicalin significantly attenuated CPB/CA-induced AKI in rats, as evidenced by the lower levels of serum creatinine, serum NGAL, and Kim1. Baicalin remarkably inhibited oxidative stress, reflected in the decreased malondialdehyde and myeloperoxidase activity, and enhanced superoxide dismutase activity and glutathione in renal tissue. Baicalin suppressed the expression of IL-18 and iNOS, and activated the Nrf2/HO-1 pathway. Conclusion: Our data indicated that baicalin mediated CPB/CA-induced AKI by decreasing the oxidative stress and inflammation in the renal tissues, and that baicalin possesses the potential to be developed as a therapeutic tool in clinical use for CSA-AKI.


2012 ◽  
Vol 63 (3) ◽  
pp. 263-270 ◽  
Author(s):  
Xiu-Quan Shi ◽  
Wei Yan ◽  
Ke-Yue Wang ◽  
Qi-Yuan Fan ◽  
Yan Zou

We tested the hypothesis that dietary fi bre (DF) has protective effects against manganese (Mn)-induced neurotoxicity. Forty-eight one-month old Sprague-Dawley rats were randomly divided into six groups: control, 16 % DF, Mn (50 mg kg-1 body weight), Mn+ 4 % DF, Mn+ 8 % DF, and Mn+ 16 % DF. After oral administration of Mn (as MnCl2) by intragastric tube during one month, we determined Mn concentrations in the blood, liver, cerebral cortex, and stool and tested neurobehavioral functions. Administration of Mn was associated with increased Mn concentration in the blood, liver, and cerebral cortex and increased Mn excretion in the stool. Aberrations in neurobehavioral performance included increases in escape latency and number of errors and decrease in step-down latency. Irrespective of the applied dose, the addition of DF in forage decreased tissue Mn concentrations and increased Mn excretion rate in the stool by 20 % to 35 %. All neurobehavioral aberrations were also improved. Our fi ndings show that oral exposure to Mn may cause neurobehavioral abnormalities in adult rats that could be effi ciently alleviated by concomitant supplementation of DF in animal feed.


2020 ◽  
Vol 23 (4) ◽  
pp. 570-579
Author(s):  
Mahboubeh Sheikhan ◽  
◽  
Mohammad Reza Kordi ◽  
Hamid Rajabi ◽  
◽  
...  

Background and Aim: Several microRNAs are involved in regulating muscle mass, which plays an essential role in hypertrophy and atrophy of skeletal muscle, The present study examined the expression of some genes as regulators of muscular atrophy following a period of inertia in rats. Methods & Materials: For this purpose, 18 male Sprague-Dawley rats were divided into three groups (Control, Exercise+inactivity, and Inactivity). The exercise+inactivity group run on the treadmill for 18 weeks and five times per week. The hindlimb of the animal was immobilized for seven days with the casting method. Soleus muscle was extracted and the expression of the genes was measured by the RT-PCR method. Univariate ANOVA and Tukey post hoc test was used to determine the differences (α=0.05). Ethical Considerations: The Ethics Committee of the Tehran University of Medical Sciences Research approved this study (Code: IR.SUMS.REC.1396.S 463). Results: Results showed that immobilization in both Exercise+ inactivity and inactivity groups, compare to the control group, increased expression of miR-1 genes (P<0.10), FOXO3a (P<0.001) and decreased expression of miR-206 (P<0.007) and IGF-1 (P<0.001). This difference was statistically significant. Conclusion: According to the results of this study, it can be said that changes in the expression of RNAs by chromatography cause changes in the expression of muscle regulating genes, and although endurance exercises have protective effects, they cannot prevent these changes.


2011 ◽  
Vol 2011 ◽  
pp. 1-7 ◽  
Author(s):  
Delira Robbins ◽  
Yunfeng Zhao

Recent studies have shown that antioxidant enzyme expression and activity are drastically reduced in most human skin diseases, leading to propagation of oxidative stress and continuous disease progression. However, antioxidants, an endogenous defense system against reactive oxygen species (ROS), can be induced by exogenous sources, resulting in protective effects against associated oxidative injury. Many studies have shown that the induction of antioxidants is an effective strategy to combat various disease states. In one approach, a SOD mimetic was applied topically to mouse skin in the two-stage skin carcinogenesis model. This method effectively reduced oxidative injury and proliferation without interfering with apoptosis. In another approach, Protandim, a combination of 5 well-studied medicinal plants, was given via dietary administration and significantly decreased tumor incidence and multiplicity by 33% and 57%, respectively. These studies suggest that alterations in antioxidant response may be a novel approach to chemoprevention. This paper focuses on how regulation of antioxidant expression and activity can be modulated in skin disease and the potential clinical implications of antioxidant-based therapies.


2019 ◽  
Vol 51 (8) ◽  
pp. 2838-2841
Author(s):  
Won Seo Park ◽  
Min Su Park ◽  
Sang Wook Kang ◽  
Seul A. Jin ◽  
Youngchul Jeon ◽  
...  

2020 ◽  
Vol 2020 ◽  
pp. 1-17 ◽  
Author(s):  
Qiqi Zhu ◽  
Haobo Li ◽  
Xiang Xie ◽  
Xiaozhen Chen ◽  
Ramoji Kosuru ◽  
...  

Myocardial ischemic postconditioning- (IPo-) mediated cardioprotection against myocardial ischemia-reperfusion (IR) injury needs the activation of signal transducer and activator of transcription 3 (STAT3), which involves adiponectin (APN). APN confers its biological effects through AMP-activated protein kinase- (AMPK-) dependent and AMPK-independent pathways. However, the role of AMPK in APN-mediated STAT3 activation in IPo cardioprotection is unknown. We hypothesized that APN-mediated STAT3 activation in IPo is AMPK-independent and that APN through AMPK-dependent STAT3 activation facilitates IPo cardioprotection. Here, Sprague-Dawley rats were subjected to myocardial IR without or with IPo and/or APN. APN or IPo significantly improved postischemic cardiac function and reduced myocardial injury and oxidative stress, and their combination further attenuated postischemic myocardial injuries. APN or its combination with IPo but not IPo alone significantly increased AMPK activation and both nuclear and mitochondrial STAT3 activation, while IPo significantly enhanced mitochondrial but not nuclear STAT3 activation. In primarily isolated cardiomyocytes, recombined globular APN (gAd), hypoxic postconditioning (HPo), or their combination significantly attenuated hypoxia/reoxygenation-induced cell injury and increased nuclear and/or mitochondrial STAT3 activation. STAT3 inhibition had no impact on gAd or gAd in combination with HPo-induced AMPK activation but abolished their cellular protective effects. AMPK inhibition did not affect HPo cardioprotection but abolished gAd cardioprotection and disabled gAd to facilitate/enhance HPo cardioprotection and STAT3 activation. These results suggest that APN confers cardioprotection through AMPK-dependent and AMPK-independent STAT3 activation, while IPo confers cardioprotection through AMPK-independent mitochondrial STAT3 activation. Joint use of APN and IPo synergistically attenuated myocardial IR injury by activating STAT3 via distinct signaling pathways.


2016 ◽  
Vol 7 (3) ◽  
pp. 409-420 ◽  
Author(s):  
T.M. Marques ◽  
E. Patterson ◽  
R. Wall ◽  
O. O’Sullivan ◽  
G.F. Fitzgerald ◽  
...  

The aim of this study was to investigate if dietary administration of γ-aminobutyric acid (GABA)-producing Lactobacillus brevis DPC 6108 and pure GABA exert protective effects against the development of diabetes in streptozotocin (STZ)-induced diabetic Sprague Dawley rats. In a first experiment, healthy rats were divided in 3 groups (n=10/group) receiving placebo, 2.6 mg/kg body weight (bw) pure GABA or L. brevis DPC 6108 (~109microorganisms). In a second experiment, rats (n=15/group) were randomised to five groups and four of these received an injection of STZ to induce type 1 diabetes. Diabetic and non-diabetic controls received placebo [4% (w/v) yeast extract in dH2O], while the other three diabetic groups received one of the following dietary supplements: 2.6 mg/kg bw GABA (low GABA), 200 mg/kg bw GABA (high GABA) or ~109 L. brevis DPC 6108. L. brevis DPC 6108 supplementation was associated with increased serum insulin levels (P<0.05), but did not alter other metabolic markers in healthy rats. Diabetes induced by STZ injection decreased body weight (P<0.05), increased intestinal length (P<0.05) and stimulated water and food intake. Insulin was decreased (P<0.05), whereas glucose was increased (P<0.001) in all diabetic groups, compared with non-diabetic controls. A decrease (P<0.01) in glucose levels was observed in diabetic rats receiving L. brevis DPC 6108, compared with diabetic-controls. Both the composition and diversity of the intestinal microbiota were affected by diabetes. Microbial diversity in diabetic rats supplemented with low GABA was not reduced (P>0.05), compared with non-diabetic controls while all other diabetic groups displayed reduced diversity (P<0.05). L. brevis DPC 6108 attenuated hyperglycaemia induced by diabetes but additional studies are needed to understand the mechanisms involved in this reduction.


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