scholarly journals Preventive Inositol Hexaphosphate Extracted from Rice Bran Inhibits Colorectal Cancer through Involvement of Wnt/β-Catenin and COX-2 Pathways

2013 ◽  
Vol 2013 ◽  
pp. 1-10 ◽  
Author(s):  
Nurul Husna Shafie ◽  
Norhaizan Mohd Esa ◽  
Hairuszah Ithnin ◽  
Abdah Md Akim ◽  
Norazalina Saad ◽  
...  
Keyword(s):  
Colorectal Cancer ◽  
Rice Bran ◽  
Anticancer Agent ◽  
Dietary Factors ◽  
Sprague Dawley ◽  
Rt Pcr ◽  
Colorectal Tumorigenesis ◽  
Chemopreventive Agent ◽  
Sprague Dawley Rats ◽  
Cox 2

Nutritional or dietary factors have drawn attention due to their potential as an effective chemopreventive agent, which is considered a more rational strategy in cancer treatment. This study was designed to evaluate the effect of IP6extracted from rice bran on azoxymethane- (AOM-) induced colorectal cancer (CRC) in rats. Initially, male Sprague Dawley rats were divided into 5 groups, with 6 rats in each group. The rats received two intraperitoneal (i.p.) injections of AOM in saline (15 mg/kg body weight) over a 2-week period to induce CRC. IP6was given in three concentrations, 0.2% (w/v), 0.5% (w/v), and 1.0% (w/v), via drinking water for 16 weeks. The deregulation of the Wnt/β-catenin signaling pathway and the expression of cyclooxygenase (COX)-2 have been implicated in colorectal tumorigenesis.β-Catenin and COX-2 expressions were analysed using the quantitative RT-PCR and Western blotting. Herein, we reported that the administration of IP6markedly suppressed the incidence of tumors when compared to the control. Interestingly, the administration of IP6had also markedly decreasedβ-catenin and COX-2 in colon tumors. Thus, the downregulation ofβ-catenin and COX-2 could play a role in inhibiting the CRC development induced by IP6and thereby act as a potent anticancer agent.

scholarly journals Cardioprotective Effect of Danhong Injection against Myocardial Infarction in Rats Is Critically Contributed by MicroRNAs

2019 ◽  
Vol 2019 ◽  
pp. 1-14 ◽  
Author(s):  
Jingrui Chen ◽  
Jing wei ◽  
John Orgah ◽  
Yan Zhu ◽  
Jingyu Ni ◽  
...  
Keyword(s):  
Myocardial Infarction ◽  
Cardiac Function ◽  
Ventricular Remodeling ◽  
Nuclear Translocation ◽  
Inflammatory Factors ◽  
Sprague Dawley ◽  
Rt Pcr ◽  
Danhong Injection ◽  
Sprague Dawley Rats ◽  
Masson Staining

Background. Danhong injection (DHI) has been mainly used for the treatment of myocardial infarction, atherosclerosis, and coronary heart disease in clinical practice. Our previous studies have shown that DHI improves ventricular remodeling and preserves cardiac function in rats with myocardial infarction (MI). In this study, we focused on the potential mechanism of DHI in protecting cardiac function in MI rats. Methods. Sprague-Dawley rats were subjected to ligation of the left anterior descending coronary artery (LAD) to prepare a myocardial infarction (MI) model. After 14 day DHI intervention, cardiac function was measured by echocardiography and myocardial fibrosis was assessed by Masson staining. Differentiated miRNAs were screened using rat immunopathology miScript miRNA PCR arrays, and their results were verified by RT-PCR, immunofluorescence, and immunoblotting. Results. DHI treatment significantly reduced infarct size and improved cardiac function and hemodynamics in MI rats by echocardiography and morphology. miRNA PCR array results showed that DHI reversed 25 miRNAs known to be associated with inflammation and apoptosis. Moreover, the expression of inflammatory factors TNF-α, IL-1β, and IL-6 was significantly reduced in the treated DHI group. Mechanistically, DHI downregulated the inflammatory transcription factor NF-κB (as reflected by inhibition of NF-κB p65 nuclear translocation and phosphorylation of the IκBα). Conclusions. DHI is effective in mitigating inflammation associated with MI by preventing NF-κB nuclear translocation and regulating miRNAs, thereby improving cardiac function in myocardial infarction rats.

scholarly journals Triptolide Attenuates Podocyte Injury by Regulating Expression of miRNA-344b-3p and miRNA-30b-3p in Rats with Adriamycin-Induced Nephropathy

2015 ◽  
Vol 2015 ◽  
pp. 1-13 ◽  
Author(s):  
Chun-Bo Jiang ◽  
Ming-Gang Wei ◽  
Yue Tu ◽  
Hao Zhu ◽  
Chun-Qing Li ◽  
...  
Keyword(s):  
Renal Cortex ◽  
Group Model ◽  
Biological Parameters ◽  
Healthy Male ◽  
Model Group ◽  
Sprague Dawley ◽  
Rt Pcr ◽  
Podocyte Injury ◽  
Sprague Dawley Rats

Objectives. We investigated the action of triptolide in rats with adriamycin-induced nephropathy and evaluated the possible mechanisms underlying its protective effect against podocyte injury.Methods. In total, 30 healthy male Sprague-Dawley rats were randomized into three groups (normal group, model group, and triptolide group). On days 7, 28, 42, and 56, 24 h urine samples were collected. All rats were sacrificed on day 56, and their blood and renal tissues were collected for determination of biochemical and molecular biological parameters. Expression of miRNAs in the renal cortex was analyzed by a biochip assay and RT-PCR was used to confirm observed differences in miRNA levels.Results. Triptolide decreased proteinuria, improved renal function without apparent adverse effects on the liver, and alleviated renal pathological lesions. Triptolide also elevated the nephrin protein level. Furthermore, levels of miR-344b-3p and miR-30b-3p were elevated in rats with adriamycin-induced nephropathy, while triptolide treatment reversed the increase in the expression of these two miRNAs.Conclusions. These results suggest that triptolide may attenuate podocyte injury in rats with adriamycin-induced nephropathy by regulating expression of miRNA-344b-3p and miRNA-30b-3p.

scholarly journals Posttraumatic therapeutic hypothermia alters microglial and macrophage polarization toward a beneficial phenotype

2016 ◽  
Vol 37 (8) ◽  
pp. 2952-2962 ◽  
Author(s):  
Jessie S Truettner ◽  
Helen M Bramlett ◽  
W Dalton Dietrich
Keyword(s):  
Brain Injury ◽  
Therapeutic Hypothermia ◽  
Macrophage Polarization ◽  
Temperature Sensitive ◽  
Sprague Dawley ◽  
Rt Pcr ◽  
M2 Microglia ◽  
Sprague Dawley Rats ◽  
Inflammatory Processes ◽  
Clinical Models

Posttraumatic inflammatory processes contribute to pathological and reparative processes observed after traumatic brain injury (TBI). Recent findings have emphasized that these divergent effects result from subsets of proinflammatory (M1) or anti-inflammatory (M2) microglia and macrophages. Therapeutic hypothermia has been tested in preclinical and clinical models of TBI to limit secondary injury mechanisms including proinflammatory processes. This study evaluated the effects of posttraumatic hypothermia (PTH) on phenotype patterns of microglia/macrophages. Sprague-Dawley rats underwent moderate fluid percussion brain injury with normothermia (37℃) or hypothermia (33℃). Cortical and hippocampal regions were analyzed using flow cytometry and reverse transcription-polymerase chain reaction (RT-PCR) at several periods after injury. Compared to normothermia, PTH attenuated infiltrating cortical macrophages positive for CD11b+ and CD45high. At 24 h, the ratio of iNOS+ (M1) to arginase+ (M2) cells after hypothermia showed a decrease compared to normothermia. RT-PCR of M1-associated genes including iNOS and IL-1β was significantly reduced with hypothermia while M2-associated genes including arginase and CD163 were significantly increased compared to normothermic conditions. The injury-induced increased expression of the chemokine Ccl2 was also reduced with PTH. These studies provide a link between temperature-sensitive alterations in macrophage/microglia activation and polarization toward a M2 phenotype that could be permissive for cell survival and repair.

Effects of Longevinex (modified resveratrol) on cardioprotection and its mechanisms of action

2010 ◽  
Vol 88 (11) ◽  
pp. 1017-1025 ◽  
Author(s):  
Subhendu Mukherjee ◽  
Diptarka Ray ◽  
Istvan Lekli ◽  
Istvan Bak ◽  
Arpad Tosaki ◽  
...  
Keyword(s):  
Rice Bran ◽  
Nuclear Translocation ◽  
Sprague Dawley ◽  
Akt Phosphorylation ◽  
Sprague Dawley Rats ◽  
Aging Properties ◽  
Considerable Debate ◽  
Enhanced Expression ◽  
Prolonged Feeding ◽  
Survival Signals

Although resveratrol has been proven to possess diverse health benefits, several recent reports have demonstrated conflicting results on some aspects of its effects, including its anti-aging properties. Considerable debate appears to exist on the dose and bioavailability of resveratrol, leading to the controversies on its effectiveness. To resolve the problem, we designed a study with a resveratrol formulation that contained resveratrol supplemented with 5% quercetin and 5% rice bran phytate (commercially known as Longevinex). These ingredients were micronized to increase the bioavailability. Sprague–Dawley rats were gavaged with either Longevinex or vehicle (5% quercetin plus 5% rice bran phytate), and rats were sacrificed after 1 or 3 months, when isolated working hearts were subjected to 30 min ischemia followed by 2 h of reperfusion. Longevinex-treated hearts, irrespective of the duration of treatments, revealed superior cardiac performance, reduced infarct size, and induction of survival signals as evidenced by increased Bcl2/Bax ratio and enhanced Akt phosphorylation. In contrast, LC3-II and Beclin were enhanced significantly after 3 months of Longevinex treatment, suggesting that autophagy occurred only after feeding Longevinex to rats for a prolonged period of time. Corroborating with the results of autophagy, Sirt1 and Sirt3 increased significantly only after 3 months of Longevinex treatment, suggesting that enhanced expression of Sirts correlated with induction of autophagy. In concert, Longevinex caused phosphorylation and nuclear translocation of FoxO1, FoxO3a, and FoxO4, indicating involvement of FoxOs with autophagy. Since Sirts and FoxOs are reliable markers of longevity, the results appear to suggest that Longevinex induces longevity after prolonged feeding via induction of autophagy, while it converts death signals into survival signals and provides cardioprotection within a relatively shorter period of time.

Low Dietary Salt Regulates Renal Vascular 20-Hydroxyeicosatetraenoic Acid Levels.

Hypertension ◽  
2000 ◽  
Vol 36 (suppl_1) ◽  
pp. 713-713
Author(s):  
Mairead A Carroll ◽  
Monica K Cheng ◽  
John C McGiff
Keyword(s):  
Sprague Dawley ◽  
Dietary Salt ◽  
Cox Inhibitors ◽  
Sprague Dawley Rats ◽  
On Line ◽  
Salt Depletion ◽  
Treatment Changes ◽  
Renal Microvasculature ◽  
Cox 2 ◽  
Renal Vascular

P110 20-hydroxyeicosatetraenoic (HETE), a prohypertensive cytochrome P450 (CYP)-derived arachidonic acid (AA) metabolite, is a principal eicosanoid of preglomerular microvessels. Vascular 20-HETE release is stimulated by angiotensin II (AII) and is subject to metabolism by cyclooxygenase (COX)-2. As dietary salt alters AII levels and COX-2 expression, we studied 20-HETE levels from microdissected arcuate and interlobular arteries and interlobar arteries obtained from male Sprague-Dawley rats fed a control (0.4% NaCl) or low salt diet (LS; 0.05% NaCl). In controls (n=6), metabolism of 14 C-AA (7μM) in the presence of NADPH (1mM) and indomethacin (INDO; 10μM) to 20-HETE was higher (P<0.05) in arcuate and interlobular arteries compared to interlobar arteries (25.2 ± 3.6 ng vs. 15.3 ± 2.3 ng/mg protein/30 min, respectively) based on reverse-phase HPLC retention times and on-line radiodetection. No regional differences in epoxide formation were evident between arcuate and interlobular arteries compared to interlobar arteries (21.9 ± 3.6 ng vs. 19.6 ± 3.7 ng/mg protein/30 min, respectively). LS treatment, for 7 days, selectively increased 20-HETE levels in interlobar arteries (24.6 ± 3.9 ng/mg protein/30 min) and increased medullary CYP-4A expression. However, in the absence of INDO, 20-HETE levels in arcuate and interlobular arteries, but not interlobar arteries, were diminished by 90% with LS treatment; changes that corresponded with induced cortical COX-2 expression. Thus, 20-HETE levels vary segmentally within the renal microvasculature. LS intake induces medullary CYP-4A expression and interlobar artery 20-HETE formation. Presumably, the diminished 20-HETE levels in arcuate and interlobular arteries, in the absence of COX inhibition, were a result of increased cortical COX-2 expression serving as a metabolic pathway for 20-HETE; the vasoconstrictor 20-HETE being metabolized by COX-2 to vasodilator prostaglandin analogs. Increased 20-HETE levels may account for the adverse effects of COX inhibitors with salt depletion.

The P2Y12 Receptor Antagonist Ticagrelor Ameliorates Pulmonary Hypertension

2021 ◽  
Author(s):  
nannan li ◽  
jie yin ◽  
yugen shi ◽  
li sun ◽  
qingshan zhang ◽  
...  
Keyword(s):  
Vascular Remodeling ◽  
Adenosine Diphosphate ◽  
P2y12 Receptor ◽  
Sprague Dawley ◽  
Rt Pcr ◽  
Sprague Dawley Rats ◽  
Haemodynamic Changes ◽  
P2y12 Receptor Antagonist ◽  
Pulmonary Arterial ◽  
Adp Receptor

Abstract Background: Pulmonary arterial hypertension (PAH) is a disease that the pulmonary artery is abnormally elevated. P2Y12 is an adenosine diphosphate (ADP) receptor and it act as the target of thienopyridine antiplatelet drugs by controlling vascular remodeling. Inhibition of P2Y12 receptor in the process of PAH was explored in this study.Methods: The PAH model was established in Sprague-Dawley rats by single subcutaneous injection of 60 mg/kg monocrotaline (MCT). The ticagrelor solution (a selective P2Y12R inhibitor) was intraperitoneally injected into rats at a dose of 14 mg/kg from the time of MCT injection to day 28.Results: In the lung tissues of PAH rats, the marked P2Y12R was detected. Treatment with ticagrelor greatly decreased P2Y12R level and efficiently abolished the upregulation of α-SMA as demonstrated by Western blot and RT-PCR. The wall thickness and occlusion score of the pulmonary arterioles showed that blockade of P2Y12R could relieve lung remodeling caused by PAH. The haemodynamic changes at 4 weeks determined that P2Y12R inhibition affected RV pressure and right heart hypertrophy.Conclusions: P2Y12R might be involved in the pathogenesis of PAH. Blockade of P2Y12R has potential in treating PAH.

Gold Nanoparticles with Dexmedetomidine Regulate GSK-3β to Reduce Neurocognitive Effects in Anesthetized Rats

2021 ◽  
Vol 21 (12) ◽  
pp. 6205-6211
Author(s):  
Xiaoxia Zhang ◽  
Zumin Xing ◽  
Jiyuan Li ◽  
Shuyi Tang ◽  
Yiwen Zhang
Keyword(s):  
Gold Nanoparticles ◽  
Mrna Expression ◽  
Intraperitoneal Injection ◽  
Control Group ◽  
Sprague Dawley ◽  
Rt Pcr ◽  
Anesthetized Rats ◽  
Sprague Dawley Rats ◽  
Gsk 3Β ◽  
Neurocognitive Effect

The aim of this study was to explore the neurocognitive effects of dexmedetomidine-loaded gold nanoparticles (AuNPs-dexmedetomidine) on anesthetized rats. Sixty Sprague Dawley rats (age, 2–3 weeks; weight, 250–280 g) were randomly divided into three groups (n = 20): the control group and two groups that received intraperitoneal injection of AuNPs-dexmedetomidine at 50 and 100 μg/kg each. Western blotting and RT-PCR were used to determine the protein and mRNA expression of GSK-3β, respectively. Compared with that in the control group, GSK-3β expression in AuNP-dexmedetomidine groups increased (P < 0.05). The protein expression of GSK-3β was higher and mRNA expression was significantly lower in the 100 μg/kg AuNP-dexmedetomidine group (P < 0.05). AuNPs-dexmedetomidine reduced the neurocognitive effect on anesthetized rats through the regulation of the GSK-3β signaling pathway.

Sepsis induces an increase in thick ascending limb Cox-2 that is TLR4 dependent

2007 ◽  
Vol 293 (4) ◽  
pp. F1187-F1196 ◽  
Author(s):  
Tarek M. El-Achkar ◽  
Zoya Plotkin ◽  
Branislav Marcic ◽  
Pierre C. Dagher
Keyword(s):  
Rat Kidney ◽  
Cecal Ligation ◽  
Thick Ascending Limb ◽  
Wild Type ◽  
Sprague Dawley ◽  
Sprague Dawley Rats ◽  
Tlr4 Gene ◽  
Cox 2 ◽  
Tlr4 Activation ◽  
Induced Changes

Cyclooxygenase-2 (Cox-2) is an inducible enzyme responsible for the formation of inflammatory prostanoids such as prostaglandins and thromboxane. Its role in the pathophysiology of inflammatory states like sepsis is increasingly recognized. Recently, we demonstrated that sepsis upregulates the endotoxin receptor Toll-like receptor 4 (TLR4) in rat kidney. Because Cox-2 is one of the downstream products of TLR4 activation, we hypothesized that sepsis-induced changes in renal Cox-2 expression are TLR4 dependent. Indeed, we show that in Sprague-Dawley rats, cecal ligation and puncture (a sepsis model) increases Cox-2 expression in cortical and medullary thick ascending loops (cTAL and mTAL, respectively) as well as inner medullary collecting ducts. These are all sites of increased TLR4 expression during sepsis. To determine the actual dependence on TLR4, we measured Cox-2 expression in wild-type and mutant mice which harbor a TLR4 gene deletion ( TLR4−/−). In wild-type mice, sepsis increased Cox-2 expression in proximal tubules, cTAL, and mTAL. In contrast, septic TLR4−/− mice showed no significant increase in cTAL or mTAL Cox-2 expression. Furthermore, renin was absent from juxtaglomerular cells of TLR4−/− mice. We conclude that the dependence of sepsis-induced renal Cox-2 expression on TLR4 is tubule specific. The TLR4-dependent Cox-2 expression is mostly restricted to cortical and medullary thick ascending loops of Henle that characteristically express and secrete Tamm-Horsfall protein.

scholarly journals COX-2-independent activation of renal (pro)renin receptor contributes to DOCA-salt hypertension in rats

2020 ◽  
Vol 319 (4) ◽  
pp. F647-F653
Author(s):  
Fei Wang ◽  
Ying Sun ◽  
Renfei Luo ◽  
Xiaohan Lu ◽  
Baoxue Yang ◽  
...  
Keyword(s):  
Renal Medulla ◽  
Immunoblot Analysis ◽  
Ang Ii ◽  
Sprague Dawley ◽  
Salt Treatment ◽  
Sprague Dawley Rats ◽  
Salt Hypertension ◽  
Cox 2 ◽  
Universal Mechanism

It has been shown that cyclooxygenase (COX)-2-dependent activation of renal (pro)renin receptor (PRR) contributes to angiotensin II (ANG II)-induced hypertension. However, less is known about the involvement of this mechanism in ANG II-independent hypertension. The goal of the present study was to test whether or not COX-2-dependent upregulation of PRR serves as a universal mechanism contributing to ANG II-dependent and -independent hypertension. Here, we examined the association between renal COX-2 and PRR during deoxycorticosterone acetate (DOCA)-salt hypertension in rats. By immunoblot analysis and immunofluorescence, renal protein expression of PRR was remarkably upregulated by DOCA-salt treatment. Surprisingly, this upregulation of renal PRR expression was unaffected by a COX-2 inhibitor, celecoxib. To address the role of renal PRR to the pathogenesis of DOCA-salt hypertension, a decoy PRR inhibitor, PRO20, was infused to the renal medulla of uninephrectomized Sprague-Dawley rats for 14 days. Radiotelemetry demonstrated effective attenuation of DOCA-salt hypertension by intramedullary infusion of a PRR inhibitor, PRO20. In parallel, DOCA-salt-induced hypertrophy in the heart and kidney as well as proteinuria were improved, accompanied with blunted polydipsia and polyuria. In contrast, intravenous infusion of PRO20 was less effective in attenuating DOCA-salt hypertension and cardiorenal injury. Together, these results suggest that COX-2-independent activation of renal PRR contributes to DOCA-salt hypertension.

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