bluuebunny/crossref_metadata_2025_split huggingface dataset:
Excess oxidative stress in genetically obese rats is independent of elevated inflammatory markers (693.11)
Authors: Ernsberger Paul , Koletsky Richard 
Published: June 2021

Oxidative stress is elevated in obese humans and rodents and may contribute to obesity‐associated conditions. These conditions include elevated blood pressure, lipids, glucose, and insulin resistance, all of which are components of the metabolic syndrome and are present in the spontaneously hypertensive obese (SHROB/Kol) rat model of prediabetes. In the present study, SHROB (N=27) were compared to lean SHR/Kol (N=11) littermates obtained from Charles River Labs (Wilmington,MA). Oxidative stress was measured by assay of peroxides by the ferric orange xylenol method (Sigma, St. Louis, MO) and nitrotyrosine by immunoassay. Plasma and organ lipid peroxides were increased up to 3‐fold in SHROB rats relative to lean SHR. Nitrotyrosine immunoreactivity in solublized kidney extracts was increased by genetic obesity (SHROB: 290±52 vs SHR: 4.1±1.3 pmol/g wet weight). Similar results were obtained for liver. The activity in the liver cytosol of the protective enzyme superoxide dismutase was not different (SHROB: 63±5 vs SHR: 53±7 U/mg protein). Another protective enzyme, catalase, was also unchanged in the liver cytosol (SHROB: 95±6 vs SHR: 93±13 U/mg protein). Thus, the enzymes responsible for breaking down reactive oxygen species fail to up‐regulate in response to increased oxidative stress in SHROB. We tested whether increased oxidative stress may reflect inflammation in SHROB rats. The inflammatory markers tumor necrosis factor alpha (TNF‐a) and interleukin‐6 in plasma did not differ between SHROB and SHR (P>0.3 for each). The anti‐inflammatory mediator adiponectin was actually increased in plasma from SHROB (N = 15) relative to SHR (N = 11; 12.2 ± 0.3 versus 9.27 ± 0.6 ug/ml). Thus the increased oxidative stress in genetically obese and hypertensive SHROB rats is not a consequence of a global inflammatory state.Grant Funding Source: Supported by Ophthalmology Education Worldwide
Caveolin‐1‐dependent regulation of cellular metabolism in breast cancer: role of Nrf‐2 and MnSOD (693.19)
Authors: Hart Peter , Minshall Richard , Bonini Marcelo 
Published: June 2021

Caveolin‐1 (Cav‐1) is a plasma membrane associated protein that participates in the regulation of various signaling pathways affecting key cellular functions. According to our studies, variations in the expression levels of Cav‐1 heavily impact breast cancer cell metabolic adaptation that concurs with epidemiologic observations, indicating that Cav‐1 loss contributes to the glycolytic shift in advanced breast cancer. Mechanistically, we found that Cav‐1 ablation in breast cancer epithelial cells (MCF‐7) results in a marked increase in reactive oxygen species (ROS) production (e.g., 4 fold increase in H2O2) derived from MnSOD overexpression. Because MnSOD expression is downstream of Nrf‐2 nuclear factor, that is itself repressed by the association with Cav‐1, we hypothesize that loss of Cav‐1 leads to an increase in Nrf‐2‐dependent transcription and upregulation of MnSOD, which in turn activates AMPK by enhancing H2O2 outflow from mitochondria. In fact, cells devoid of Cav‐1 were shown to turn glycolytic in an H2O2‐ and AMPK‐dependent manner. Cav‐1 reconstitution or silencing of Nrf‐2 dampened AMPK activation and restored mitochondrial polarization along with decreasing the glycolytic rate. Relevantly, cells obtained from breast cancer patients at different stages of the disease showed progressive loss of Cav‐1 parallel to the upregulation of MnSOD, Nrf2, activated AMPK and a strong shift towards a predominantly glycolytic metabolism. Additionally, immunofluorescent staining of breast cancer tissue as compared to healthy controls recapitulated these findings. In conclusion, we propose that Cav‐1 may serve a tumor suppressive role by imposing metabolic restrictions for cancer progression via repressing Nrf2, MnSOD and ROS‐induced AMPK activation.Grant Funding Source: Supported by Dept of Defense (W911NF‐07‐R‐0003‐04), T32 Training Grant (T32HL072742‐09)
Oxidant‐antioxidant parameters in different sessions of hyperbaric oxygen therapy (693.2)
Authors: Ortiz‐Villegas Miguel , Navarro‐Barrientos Maria , Kormanovski Alexander , Castillo‐Hernandez Maria , Lara‐Padilla Eleazar , Guevara‐Balcazar Gustavo 
Published: June 2021

Hyperbaric oxygen therapy (HBO) cause and increment of oxygen into the blood, through a body intermittent exposure to 100% oxygen at pressures greater than one atmosphere of pressure; it produces several therapeutic effects of which the most studied are: carbon monoxide poisoning , acute influences the vascular reactivity and reduces the heart rate ( 10 to 15% ), increases collagen production , stimulates neoangiogenesis modulates nitric oxide production , increases the uptake of reactive oxygen species and especially in the treatment of arterial gas embolism and decompression sickness.It is also well known that oxygen breathing over 1 ATA may increase reactive oxygen species (ROS). This is very important as the molecular basis for different molecular mechanisms The goal of this paper is to measure several parameters oxidant/ antioxidant in the heart of rats with HBO.Methods: Male Wistar rats were used and were exposed to HBO at 2 atmospheres with 100% O2 for 60 minutes. TAS, TBARS , SOD , GPX , GPH , CAT and NT were measured in the left and right heart .Results: Finding an elevation of TBARS in heart left and right since the first session until normalized in 20 session. TAS, GPX, GSH and CAT concentration were lower at the beginning than the control at the 20 session.Grant Funding Source: COFAA / IPN
The effects of high energy radiation on the vestibular and immune function in rats (693.22)
Authors: Scott Ansley , Shenwu Ming , Tang Xuehui , Wang Jun , Yang Chunli , Zhou Wu , Zhu Hong , Mao Jinghe 
Published: June 2021

The objective of the project is to study radiation effects on the vestibular and immune systems in rats. It is proposed that high energy radiation will compromise vestibular/balance system and immune function since nasopharyngeal cancer patients experience post‐irradiation vertigo and whole body radiation therapy causes immune suppression. However, the underlying mechanisms are not fully understood.Sprague‐Dawley rats were exposed to different doses of either unilateral cranial using 6 MeV electron beam (0 to 60Gy) or whole body using 18 MeV electron beam (0 to 10 Gy). For vestibular study, seven days post irradiation, single unit recording of vestibular afferent activity was performed. A total of 309 horizontal semicircular canal afferents’ responses to sinusoidal earth‐horizontal rotations (~1Hz) were analyzed. For immune function study, total RNAs were extracted from immune organs such as thymus and spleen. The genes involved in Stress and Toxicity PathwayFinder were examined using RT2 ProfilerTM PCR Array.Preliminary analysis shows that electron irradiation caused significant decreases in the gains of the irregular horizontal semicircular canal afferents. The gene expression profiles indicated significant changes in oxidative stress, DNA damage and repair as well as apoptosis related genes.In conclusion, these results indicate that irradiation exposure induces specific functional deficiency of the vestibular and immune system in rats.Grant Funding Source: Supported by NASA MSI EPSCoR (NNX12AK85A and NNX13AB31A), NIH R01DC012060 (HZ), NIH R01DC008585 (WZ)
Lipopolysaccharide‐induced histone deacetylase activity increases paracellular permeability in human lung microvascular endothelial cells (695.4)
Authors: Joshi Atul , Barabutis Nektarios , Thangjam Gagan , Birmpas Charalampos , Catravas John 
Published: June 2021

Objective: Lipopolysaccharide causes disruption of the endothelial barrier and increases trans‐endothelial permeability. Inhibition of heat shock protein 90 (Hsp90) protects and restores LPS‐mediated trans‐endothelial hyper‐permeability. Hyper‐acetylation of Hsp90 suppresses its chaperone function suggesting a role of HDAC in LPS‐mediated trans‐endothelial permeability. Therefore, we investigated the role of HDAC in LPS‐mediated trans‐endothelial permeability in human lung microvascular endothelial cells (HLMVEC). Method: HDAC activity was measured using the Flour‐de‐lys assay kit and HLMVEC barrier function was measured using gold‐plated electric cell‐substrate impedance sensing (ECIS) arrays. Results: Whole cell lysates from HLMVEC exposed to LPS (0.2, 1 or 5 EU/ml) showed significant increase in HDAC activity compared to vehicle‐treated cells. Cell fractionation revealed that LPS induced HDAC activity in both the cytoplasmic and the nuclear extracts. This LPS‐induced HDAC activity was not inhibited by pre‐treatment with the PI3k/Akt inhibitor, Ly294002 (5µM) or the Hsp90 inhibitor AUY‐922 (2µM), indicating that LPS stimulates HDAC activity independently of Hsp90 or Akt. Additionally, pre‐treatment with either HDAC inhibitor (Trichostatin (TSA), 1 µM or Panobinostat (LBH), 1 µM) protected HLMVEC monolayers from LPS‐mediated hyper‐permeability and attenuated Hsp90 chaperone function by disrupting Hsp90‐CDC37 interaction. Conclusion: LPS induces HDAC activity to promote trans‐endothelial hyper‐permeability possibly via de‐acetylation and activation of the Hsp90 chaperone function. (Supported by HL093460 and HL101902)Grant Funding Source: Supported by HL093460 and HL101902
Role of T cells in LPS‐induced lung inflammation and dysfunction (695.5)
Authors: Kvietys Peter , Nader Moni 
Published: June 2021

Common pathophysiologic features of ALI/ARDS are pulmonary leukocyte infiltration, interstitial edema, and impaired gas exchange. A major component of the alveolar infiltrate is polymorphonuclear leukocytes (PMN), which are believed to be the innate immune cells responsible for the pulmonary dysfunction. In a murine LPS (i.t.) model, our experiments indicated that, at 24 hrs after LPS challenge, PMN were present in the pulmonary alveoli and there was evidence of pulmonary dysfunction, i.e., increased vascular protein leak (Evans blue) and systemic hypoxia (arterial pO2). Interestingly, the infiltrated leukocytes were not all PMN; approximately half of the leukocyte population consisted of T cells (immunohistochemistry targeting CD3+ cells). In order to determine whether CD4+ T cells were involved in the pulmonary dysfunction in our LPS model, a genetic blockade approach was used (mice deficient in CD4+ T cells). The results of these experiments indicated that the increase in vascular protein leak induced by LPS in wild type (WT) mice was completely prevented when CD4+ T cell deficient (CD4‐) mice were used. The LPS‐induced systemic hypoxemia was also substantially blunted in the CD4+ T cell deficient mice. These observations provide strong support for the hypothesis that CD4+ T cells play an important role in the pathogenesis of ALI/ARDS.Grant Funding Source: KACST‐ MED1672‐44
In vitro (organ chambers) effects caused by respiratory acidosis on vascular reactivity of the rat aorta (695.6)
Authors: Augusto Viviane , Nadai Tales , Silveira Ana Paula , Albuquerque Agnes , Vento Daniella , Rodrigues Alfredo , Celotto Andrea , Évora Paulo 
Published: June 2021

Resumo In vitro (“organ chambers”) effects caused by respiratory acidosis on vascular reactivity of the rat aorta Viviane S. Augusto, Tales R. Nadai, Ana Paula S. Cassiano, Agnes A. S. Albuquerque, Daniella A. Vento, Alfredo J. Rodrigues, Andrea C. Celotto, Paulo R. B. Evora Department of Surgery and Anatomy, Ribeirão Preto School of Medicine University of São Paulo, Brazil The mechanisms by which pH influences on vascular tone or their response to certain agonists are not fully understood, but there is evidence to suggest the involvement of nitric oxide (NO), prostacyclin (PGI2), potassiumchannels and calcium flux. The present investigation was carried out to study in vitro (“organ chambers”) effects caused by respiratory acidosis (RA) on vascular reactivity of the aorta from Wistar rats, and the endothelium‐dependent mechanisms involved. Many assays were carried out untiladoptingorgan baths bubbling a gas mixture of CO2/(40%)/02 (60%), for the construction of pH‐response curves (pH 7.4 at 6:6) registering in isometric pre‐aortic rings contracted with phenylephrine (10‐6M). As main results: 1) Relaxations were seen only in endothelial rings; 2) Endothelium‐dependent relaxations were inhibited by incubation for 30 min with indomethacin (10‐5 M), L‐NAME (10‐4 M) and tetraethylammonium (10‐3 M). These data allow concluding by the suitability of the method and the dependence of endothelial vascular response induced by extracellular RA, including the three known mechanisms of vasodilation: cAMP, cGMP and hyperpolarization.Grant Funding Source: Supported by CNPq, FAEPA, CAPES, FAPESP
Vascular phenotype of the STE20/SPS1‐related proline/alanine‐rich kinase targeted hypotensive mouse model of Gitelman syndrome (697.6)
Authors: Siew Keith , Maguire Janet , Davenport Anthony , O'Shaughnessy Kevin 
Published: June 2021

Reduced renal Na+‐Cl‐ cotransporter (NCC) activity in Gitelman syndrome leads to salt‐wasting hypotension. SPAK phosphorylates NCC and Na+‐K+‐2Cl‐ cotransporter (NKCC1) increasing activity. Our SPAK T243A loss‐of‐function knock‐in (SPAK‐KI) mice recapitulate human Gitelman syndrome by reducing phospho‐NCC. Published data on SPAK knock‐out (SPAK‐KO) mice show reduced aortic phospho‐NKCC1 and contractility, that we hypothesised would be recapitulated by SPAK‐KI. Therefore we have investigated the vascular phenotype of SPAK‐KI.To assess the influence of altered NKCC1 activity, myograph mounted aortae (n=11 per group) were incubated with 10μM bumetanide (Bmt) to inhibit NKCC1 or 0.1%v/v ethanol (EtOH) control. Cumulative concentration‐response curves to phenylephrine were used to determine pD2 (‐log10 of the EC50) and maximum response (EMAX) values.We found no significant difference (P>0.05) in aortic contractility between SPAK‐KI and wildtype (WT) littermates in the absence or presence of Bmt.

Group
WT (EtOH)
WT (Bmt)
SPAK‐KI (EtOH)
SPAK‐KI (Bmt)

pD2 (‐log EC50)
6.18 ± 0.10
6.17 ± 0.08
5.99 ± 0.12
6.23 ± 0.11

Emax (mN/mm)
3.3 ± 0.5
3.3 ± 0.5
4.7 ± 0.9
3.3 ± 0.7

Basal (nN/mm)
21.0 ± 1.2
20.5 ± 1.3
20.9 ± 1.2
21.0 ± 1.5

Data are mean ± SEM In conclusion, vascular contractility remains intact in the SPAK‐KI despite functional or pharmacological NKCC1 inhibition. We suggest the reported phenotypic differences of the SPAK‐KO results from their alternative model design. Recent data support physiological roles for newly discovered SPAK isoforms that are known to be absent in protein‐ablated SPAK‐KO but present in protein‐intact SPAK‐KI. These isoforms may play as yet unexplored roles in vascular contractility.Grant Funding Source: Supported by the British Heart Foundation
Chronic treatment with antioxidant flavonoids improves the vascular reactivity in mesenteric arteries from obese rats (700.10)
Authors: Priviero Fernanda , Rojas‐Moscoso Julio , De Souza Verônica , Ravos Amanda , Claudino Mario , Rocha Thalita , Carvalho Patrícia 
Published: June 2021

Impaired vascular relaxation is often observed in obese individuals, which is likely associated to the decreased NO bioavailability and increased oxidative stress. Antioxidant flavonoids are usually proposed as a therapy against the increased oxidative stress. However, glycosylated flavonoid bioavailability is limited because of its low capacity of intestinal absorption. We aimed to evaluate the effects of a chronic treatment with glycosylate hesperidin (gHD) and its enzymatically hydrolyzed compound hesperetin (HT) on the vascular relaxation of obese rats. After the 4th week of life, rats were fed with standard chow or high fat diet (59% of total fat) + fructose (1mg/ml) for 12 weeks. gHD or HT were administrated by gavage (1ml/rat/day) during the last 8 weeks. Next, we measured body weight and epididimal weight and the superior mesenteric artery was removed in order to obtain concentration response curves to acetylcholine. Endothelium‐independent relaxation was evaluated by a single concentration of sodium nitroprusside (SNP). High fat diet + fructose caused an increase in the final body weight and epididimal fat, which was not prevented by the flavonoids (Final body weight: Control: 414 ± 15g, High Fat Diet: 504 ± 17g, gHD: 497 ± 39g, HT: 536 ± 22g; Epididmal fat: Control: 7 ± 1g, High fat diet: 19 ± 2g, gHD: 15 ± 1g, HT: 21 ±2g) Further, obese rats showed decreased vascular relaxation to acetylcholine (pEC50: 7.35 ± 0.35 vs 5.78 ± 0.42, for control and high fat diet, respectively). However, chronic treatment with antioxidant flavonoids prevented this decrease (pEC50: 6.97 ± 0.11 and 7.53 ± 0.05, for gHD and HT, respectively), suggesting that the impaired relaxation is because of the increased pro oxidant agents. Maximal responses to acetylcholine were similar among the groups. No differences were seen in the relaxant response to 1uM of SNP. In conclusion, either gHD or HT prevented the impaired vascular relaxation observed in obesity with no changes in the body weight and epididimal fat accumulation.Grant Funding Source: Financial Support: FAPESP and CNPq
Low‐level lead exposure increased bioavailability of nitric oxide mediated by angiotensin II and PI3K/AKT pathway in rat aorta (700.2)
Authors: Fiorim Jonaina , Ribeiro Rogério , Azevedo Bruna , Simões Maylla , dos Santos Leonardo , Padilha Alessandra , Alonso Maria , Salaices Mercedes , Stefanon Ivanita , Vassallo Dalton 
Published: June 2021

We previously demonstrated that 7‐day exposure with a low concentration of lead acetate increases blood pressure (BP) and nitric oxide (NO) bioavailability, which could be a compensatory mechanism in the initial stages of lead exposure.We investigated the involvement angiotensin II and PI3K/AKT pathway in this increased NO bioavailability. Wistar rats were treated with lead (1st dose 4 μg/100g and, subsequent doses 0.05 μg/100g, i.m cover daily loss) or vehicle. After lead treatment, blood levels were of 9.98μg/dL. In aortic rings from lead‐treated rats, phenylephrine (PHE 10‐10‐10‐4M) contractile responses were reduced; L‐NAME (LN‐10µM) increased PHE responses more in lead‐treated rats than untreated rats. Wortmannin (WT‐0,1µM) and PD123319 (PD‐1µM) normalized PHE responses in treated rats, and in presence of either WT, PD or losartan (LOS) that effect of LN on reactivity from lead treated group was blunted. Lead also increased release of NO, which was blocked by LOS, WT and PD. Our results suggest the involvement of angiotensin II and PI3K/AKT pathway in increased NO bioavailability in lead rats. This might be an alternative way to increase the NO bioavailability, as a compensatory mechanism against the increased SBP in the early stages of lead exposure.Grant Funding Source: CAPES, CNPq and FAPES.
Pendrin localizes to the adrenal medulla where it modulates catecholamine release (701.1)
Authors: Lazo‐Fernandez Yoskaly , Aguilera Greti , Beierwaltes William , Verlander Jill , Kim Young , Pacak Karel , Plotsky Paul , Wall Susan 
Published: June 2021

Pendrin is an aldosterone‐sensitive, Na+‐independent Cl‐/HCO3‐ exchanger expressed in intercalated cells within the renal cortex where it modulates blood pressure. Since pendrin gene ablation stimulates the release of renin, but not aldosterone, we hypothesized that pendrin is expressed in the adrenal gland and modulates adrenal function. Thus, we examined rat and mouse adrenal pendrin mRNA and protein abundance by PCR, immunoblot and immunohistochemistry and examined adrenal responses in wild type and pendrin null mice. Pendrin protein was detected in adrenal lysates from wild type, but not pendrin null mice. In both mice and rats, we observed pendrin mRNA and protein in the adrenal medulla but not in the adrenal cortex. Since the adrenal medulla produces catecholamines, further experiments examined plasma epinephrine responses to 5 and 20 min of immobilization stress in wild type and pendrin null mice. Basal epinephrine concentration was similar in wild type and pendrin null mice. Immobilization stress increased epinephrine in both groups, but responses were ~50% higher in pendrin null vs wild type after either 5 or 20 min of immobilization stress (20 min: KO, 1562 ± 263, n=4, vs WT, 1041 ± 129 pg/ml, n=6, P < 0.05). We conclude that pendrin is expressed in the adrenal medulla where it may blunt stress‐induced epinephrine release.Grant Funding Source: Supported by NIH
Angiotensin II modulates sex steroid receptors and their metabolizing enzymes in rat cardiac fibroblast (701.10)
Authors: Madhavpeddi Lakshmi , Gonzales Rayna , Hale Taben 
Published: June 2021

Sex steroids influence angiotensin II (AngII)‐induced cardiac remodeling; however, the importance of local sex steroid metabolism in this process is not known. We previously demonstrated that AngII increased aromatase levels, the enzyme that converts testosterone (T) to 17β‐estradiol, in cultured coronary vascular smooth muscle cells. In the present study we investigated the impact of AngII on sex steroid receptor and enzyme expression in primary rat cardiac fibroblasts. Fibroblasts were isolated from adult male rats and treated at P1 in 2% charcoal‐stripped FBS with AngII or vehicle (18h), followed by T (6h) in the presence or absence of anastrozole (aromatase inhibitor; 6.5h). Cardiac fibroblasts expressed receptors ERα, ERβ, and AR, as well as the enzymes aromatase and 5α‐reductase. AngII significantly reduced mRNA expression of ERβ. 5α‐reductase, AR, and ERβ levels increased when anastrazole was administered with T. This is the first demonstration that cardiac fibroblasts express the enzymes and receptors necessary for local sex steroid metabolism and action. Enzymes and receptor levels are differentially impacted by AngII. Additionally, aromatase inhibition in the presence of T alters steroid receptor and 5α‐reductase (testosterone metabolizing enzyme) levels. Given the major role of the fibroblast in pathogenic cardiac remodeling, the relative balance of T to estrogen in these cells may play an important role in the development of AngII‐mediated fibrosis.Grant Funding Source: Supported by American Heart Association
Effect of oleanolic acid on the regulation of water, electrolyte and the renin system (701.4)
Authors: Choi Yoon Hee , Kho Min Chul , Park Ji Hun , Cho Kyung Woo , Kang Dae Gill , Lee Ho Sub 
Published: June 2021

Effect of oleanolic acid on the regulation of water, electrolyte and the renin system Yoon Hee Choi1,2, Min Chul Kho1,2, Ji Hun Park2,3, Kyung Woo Cho1,2, Dae Gill Kang1,2,3, Ho Sub Lee1,2 1Professional graduate school of Oriental Medicine, Wonkwang University, Iksan, Jeonbuk, 570‐749, Republic of Korea 2 Hanbang Body‐fluid Research Center, Wonkwang University, Shinyong‐dong, Iksan, Jeonbuk, 570‐749, Republic of Korea 3Department of Food Industry Convergence, Wonkwang University, Iksan, Jeonbuk 570‐749, Republic of Korea ABSTRACT Oleanolic acid is an active ingredient of variable plants including medicinal herbs and edible vegetables. Previously, it was shown that oral intake of oleanolic acid accentuates the atrial natriuretic peptide (ANP) system. Oleanolic acid increases cardiac ANP synthesis, plasma levels, and secretion. The purpose of the present study was to identify the effects of oleanolic acid on the regulation of fluid and electrolyte homeostasis and renal hormone balance. Experiments were performed in rats housed in metabolic cage and Oleanolic acid was administered orally everyday for 7 days. Oleanolic acid increased urinary excretion of Na+, Cl‐, and K+ . Oleanolic acid also increased urinary excretion of creatinine and clearance for creatinine. Furthermore, oleanolic acid suppressed plasma renin activity and renal renin contents. These findings suggest that oleanolic acid increases glomerular filtration rate and urinary excretion of water and electrolytes via suppression of the renin‐angiotensin system. Thus, this provides experimental evidence for beneficial effects of oleanolic acid in the cardiovascular system.Keyworlds : Oleanolic acid;Renin‐angiotensin system;Glomerular filtration rate;Urinary; Renin activity