bluuebunny/crossref_metadata_2025_split huggingface dataset:
High dietary iron and radiation exposure increase biomarkers of oxidative stress in blood and liver of rats
Authors: Morgan Jennifer L. L. , Theriot Corey A. , Wu Honglu , Smith Scott M. , Zwart Sara R. 
Published: June 2021

Radiation exposure and increased iron (Fe) status independently cause oxidative damage that can result in protein, lipid, and DNA oxidation. During space flight astronauts are exposed to both increased radiation and increased Fe stores. Increased body Fe results from a decrease in red blood cell mass and the typically high Fe content of the food system. In this study we investigated the combined effects of radiation exposure (0.375 Gy of Cs‐137 every other day for 16 days; a total of 3 Gy) and high dietary Fe (650 mg Fe/kg diet vs. 45 mg Fe/kg for controls) in Sprague‐Dawley rats (n=8/group). Liver and serum Fe were significantly increased in the high dietary Fe groups. Likewise, radiation exposure increased serum ferritin and Fe concentrations. These data indicate that total body Fe stores increase with both radiation exposure and excess dietary Fe. Hematocrit decreased in the group exposed to radiation, providing a possible mechanism for the shift in Fe indices after radiation exposure. Markers of oxidative stress were also affected by both radiation and high dietary Fe, evidenced by increased liver glutathione peroxidase (GPX) and serum catalase as well as decreased serum GPX. Our results reveal preliminary indications of the synergistic effects of protracted (fractionated) radiation exposure and increased dietary Fe, warranting further study.Grant Funding Source: This research was funded by the NASA Human Research Program. Dr. Morgan's efforts and travel are supported through an appointment to the NASA Postdoctoral Program at the Johnson Space Center, administered by Oak Ridge Associated Universities through a contract with NASA
Ratio of primary to secondary oxidation products and time of exposure correlate with lipid accumulation in murine adipocytes
Authors: Skinner Joanna Ponder , Dingels Nicole , Santanam Nalini , Penumetcha Meera 
Published: June 2021

The objective of this study was to investigate if the level of oxidation of soybean oil determines the accumulation of lipids in 3T3‐L1 adipocytes.MethodsSoybean oil (SO) was unheated or heated for 3, 6 or 9 hours at 190°C to generate oils with increasing levels of oxidation as determined by the levels of conjugated dienes (CD) and conjugated trienes (CT). 3T3‐L1 cells were grown to confluence in 24 well plates and then exposed to DMEM supplemented with or without 0.1%, 0.01% and 0.001% of heated or unheated SO for 24 hrs either prior to or, after differentiation. After treatment, cells were stained with oil red O to determine the accumulation of lipids.ResultsProgressive heating of soybean oil created oils with increasing amounts of oxidized lipids (ratio of CD/CT was 1.92, 2.33, 3.1 and 3.56 for the unheated, 3hr, 6hr and 9hr heated oils, respectively). The intensity of oil red O staining was similar in 3T3‐L1 cells that were treated with vehicle or unheated oil for 24hr in undifferentiated cells but was lesser in the cells treated with 3hr heated SO. More interestingly, there was no oil red staining when cells were treated with the 6hr and 9hr heated oils, suggesting a loss of lipid accumulation. In experiments where SO was added to differentiated 3T3‐L1 cells for 24 hrs, there was no obvious effect of the oils on oil red O staining.ConclusionThese results demonstrate that exposure of pre‐adipocytes to oils with higher ratios of oxidized lipids inhibits the adipocyte lipid accumulation. Since this effect is not seen in cells that are differentiated, it suggests that heated oils could be suppressing regulators of adipocyte differentiation.Grant Funding Source : None
A‐type procyanidin dimers, trimers, and tetramers from cranberries transported across monolayers of human Intestinal epithelial Caco‐2 cells
Authors: OU Keqin , Percival Susan S. , Zou Tao , Khoo Christina , Gu Liwei 
Published: June 2021

A‐type procyanidin oligomers in cranberries are known to inhibit the adhesion of uropathogenic bacteria. B‐type procyanidins dimers and trimers are absorbed by humans. The absorption of A‐type procyanidins from cranberries in humans has not been demonstrated. This study examined the transport of A‐type cranberry procyanidin dimers, trimers, and tetramers on differentiated human intestinal epithelial Caco‐2 cell monolayers. Procyanidins were extracted from cranberries and purified using chromatographic methods. Fraction I contained predominantly A‐type procyanidin dimer A2 [epicatechin‐(2‐O‐7, 4‐8)‐epicatechin]. Fraction II contained primarily A‐type trimers and tetramers, with B‐type trimers, A‐type pentamers, and A‐type hexamers being minor components. Fraction I or II in solution were added onto the apical side of the Caco‐2 cell membranes. The media at the basolateral side of the membranes were analyzed using HPLC‐MSn after two hours. Data indicated that procyanidin dimer A2 in fraction I and A‐type trimers and tetramers in fraction II traversed across Caco‐2 cell monolayers with transport ratio of 0.59%, 0.37%, and 0.23%, respectively. This study demonstrated A‐type dimers, trimers, and tetramers were transported across Caco‐2 cells at low rates, suggesting they could be absorbed by humans after cranberry consumption.This research was supported in part by Ocean Spray Cranberries, Inc.
Safety evaluation of MJ33 as a potential in vivo inhibitor of NADPH oxidase (NOX2) activation
Authors: Lee Intae , Zagorski John , Dodia Chandra , Feinstein Sheldon , Fisher Aron B. 
Published: June 2021

Inhibition of NOX2 has been proposed for the treatment of acute lung injury (ALI) by preventing the generation of reactive O2 species (ROS). MJ33, a fluorinated phospholipid analogue, functions as a potential ALI therapeutic agent by inhibiting the phospholipase A2 (PLA2) activity that is required for NOX2 activation (J. Biol. Chem., 286:11696, 2011). Long‐term toxicity studies were performed to evaluate the feasibility for this use of MJ33. MJ33 incorporated into mixed unilamellar liposomes was injected either intra‐tracheally (IT) or intravenously (IV) in single or multiple doses, up to 25μmol for a 20g mouse. Mice treated with MJ33 up to 10μmol did not show any obvious changes in clinical score, general appearance, activity level, hair quality, body temperature or feces. At 5μmol by IT or IV route, weight loss was <10% and mice recovered with a subsequent small weight gain. Hematocrit and lung wet to dry weight ratio were not altered by MJ33. Weight loss was greater with 10μmol (in multiple doses: 4× 2.5μmol) but was not progressive. Thus, the maximal tolerated dose (defined as causing >15% reduction in body weight) was 0.42μmol/g body wt (~2000 times higher than the dose shown to inhibit PLA2 activity). LD50 was 1.3μmol/g body wt. These results indicate a high margin of safety for administration of MJ33 in the intact mouse.Supported by NHLBI R01 HL075587
Rimcazole Attenuates the Cocaine‐Induced Stimulation of Mesolimbic Dopamine related to its Abuse and Dependence
Authors: Mereu Maddalena , Chun Lauren E , Hiranita Takato , Cao Jian Jing , Newman Amy , Katz Jonathan L , Tanda Gianluigi 
Published: June 2021

Rimcazole (RIM) is a sigma receptor (σR) antagonist that also has affinity for the dopamine (DA) transporter (DAT). Despite this DAT affinity, RIM lacks stimulant effects and dose‐dependently attenuates ambulatory effects of cocaine (COC). RIM and its analogs decrease COC self‐administration in rats (JPET 339: 662), an effect that is obtained neither with selective σR antagonists nor standard DAT blockers.Thus, we tested RIM (1–17 mg/kg i.p.) alone and in combination with increasing doses of COC that maintain self‐administration (0.1–1.0 mg/kg i.v.), on stimulation of mesolimbic DA in Sprague Dawley rats implanted with a microdialysis probes in the accumbens shell.RIM dose‐dependently attenuated COC‐induced stimulation of DA levels at doses that had no effects on DA levels when administered alone. Previous studies suggest that the attenuation of COC self‐administration produced by RIM is due to the combined actions at σRs and the DAT as combinations of selective DAT inhibitors and selective σR produced effects like those or RIM.Thus, the present study indicates that not only can combined DAT and σR inhibition decrease cocaine self administration, it also can decrease its neurochemical substrates suggesting that combined actions at these two targets may serve as a new strategy for discovery of novel compounds for development as medications for stimulant abuse.
The discriminative stimulus effects of bretazenil and lorazepam in rats trained to discriminate pentobarbital from saline
Authors: Hulin Mary Worrel , Winsauer Peter J. 
Published: June 2021

Low‐efficacy positive modulators of the GABAA receptor, such as bretazenil, could potentially treat anxiety disorders with less liability for abuse and dependence than traditional benzodiazepines. For this reason, bretazenil was compared with pentobarbital and lorazepam (high‐efficacy positive modulators) in rats trained to discriminate 10 mg/kg of pentobarbital from saline under a fixed‐ratio 20 schedule of food reinforcement. To establish a dose‐response curve in a single session, a cumulative‐dosing procedure was used in which subjects received increasing doses prior to each of four test components. Full substitution was defined as greater than 80% of total lever presses occurring on the pentobarbital‐associated lever. When increasing doses of pentobarbital were administered, pentobarbital‐lever responding increased up to doses that decreased response rate. Unlike pentobarbital, lorazepam only substituted for pentobarbital at doses that decreased response rate. Bretazenil fully substituted in each subject tested. Furthermore, ineffective doses of bretazenil were able to shift the lorazepam dose‐response curve upward and to the left. Together, these data indicate that bretazenil produces pentobarbital‐like discriminative stimulus effects and enhances the effects of lorazepam, indicating that this combination could be clinically useful for long‐term treatment of anxiety disorders.This work supported by an NIH grant from the National Institute on Alcohol Abuse and Alcoholism AA019848‐01
L‐arginine recycling and endothelial vasomotor function
Authors: Chennupati Ramesh , Meens Merlijn , Janssen Ben , Lamers Wouter , De Mey Jo , Koehler S. Eleonore 
Published: June 2021

ObjectiveTo assess whether impaired L‐arginine resynthesis or degradation affects endothelial vasomotor function.MethodsEndothelium‐selective argininosuccinate synthetase‐ (ASS‐KO) and arginase1‐deficient (Arg1‐KO) mice were generated by crossing ASSfl/fl and Arg1fl/fl mice with Tie2Cre mice. Mean arterial blood pressure (MAP) was recorded in conscious 34‐ week‐old male mice using intra‐arterial catheter. Vasomotor responses were studied in saphenous arteries of 12‐ and 34‐weekold KO and floxed control animals (“WT”) by wire‐myography.ResultsBasal MAP was similar in WT and both KO strains. MAP was increased to the same extent in all genotypes by depletion of circulating L‐arginine (200 U arginase1 intravenously) or inhibition of NOS activity (L‐NAME, 10mg/kg). Optimal arterial diameter, contractile responses to phenylephrine, and relaxing responses to acetylcholine and sodium nitroprusside were also similar in WT and KO mice.ConclusionAbsence of endothelial arginine recycling or arginine degradation from citrulline does not affect blood pressure and vasomotor responses in small arteries.Supported by NHF‐grant 2008B107
Brain‐derived Neurotrophic Factor Mediates the Neuro‐protective Effects of Estrone after Brain Injury
Authors: Gatson Joshua W. , Simpkins James , Wigginton Jane , Liu Ming-Mei , Wolf Steven , Minei Joseph 
Published: June 2021

IntroductionEstrone (predominant estrogen in postmenopausal women) has shown to be a promising neuro‐protective agent in stroke and other traumatic injuries. The overall goal of this project was to determine if ERK signaling and brain‐derived neurotrophic factor (BDNF) mediates the protective effects of estrone after TBI.MethodsIn this study, male rats were treated with either placebo (corn oil; n=8) or estrone (0.5mg/kg; n=8) at 30 minutes after TBI. Injury was induced using the controlled cortical impact device. Control (n=8) and sham (craniotomy only; n=8) groups were also included in this study. At 72 hours following injury, the brains were fixed and stained for TUNEL + cells. To test for phospho‐ ERK, phospho‐CREB, and BDNF levels, total protein was isolated from brain tissue and Western analysis was used.ResultsEstrone significantly decreased the levels of TUNEL + staining (p<0.01). In addition, in the estrone treated groups there was a significant increase in the levels of phospho‐ERK (p<0.02) and CREB (p<0.05). Also, the levels of BDNF (p<0.007) were significantly increased in the estrone treated groups at 72 hours after injury.ConclusionEstrone given after injury is protective and results in an increase in ERK signaling and subsequent BDNF expression. These results suggest that other estrogens in addition to estradiol may afford individuals protection from secondary brain injury after TBI.
Decreased Telomerase Activity Converts the Mechanism of FMD from NO to H2O2 in Human and Mouse Arterioles
Authors: Beyer Andreas M. , Gutterman David D. 
Published: June 2021

Reactive oxygen species (ROS) are important modulators of vascular reactivity. In disease, the mechanism of endothelium‐dependent vasodilation can shift from NO to hydrogen peroxide (H2O2). Reduced telomerase activity (TA) has been linked to increased ROS production. Animals lacking telomerase develop hypertension but the underlying effects on the vasculature are unknown. We hypothesized that decreases in TA are associated with elevated ROS and a change in the mechanism of endothelium‐dependent dilation from NO to H2O2. We postulate that this shift in dilator mechanism is conserved across species (mouse to human).Murine mesenteric arteries (~200 μm) were isolated and flow‐mediated dilation (FMD) was studied ex‐vivo (pressure gradient 0–100 cm H2O). Inhibition of TA shifted the mediator of FMD from NO to H2O2 (% Max dilation at 100 cm H2O: Vehicle 72±9; +L‐NAME −8±8; +Catalase 92±6; TA inhibitor BIRB1532 10 μM 12–15 hours 84±7; +L‐NAME 81±10*; +Catalase −7±8* n≥4; * P <0.05 one way ANOVA vs. Vehicle). Resistance vessels (~200 μm) from the human adipose responded in a similar manner. Decreased TA shifted the mechanism of FMD from NO to H2O2 (% Max dilation at 100 cm H2O: Vehicle 88±3; +L‐NAME −39±2; +Catalase 83±3; BIRB1532 88.7±6; +L‐NAME 85±2*; +Catalase 34±5* n≥3; * P <0.05 one way ANOVA vs. Vehicle).We conclude that telomerase may play a critical role in acute modulation of microvascular function across species.
Effect of aerobic exercise on capillary and vascular endothelial growth factor in rat soleus muscle
Authors: Murakami Shinichiro , Fujita Naoto , Kondo Hiroyo , Tanaka Masayuki , Sakita Masahiro , Fujino Hidemi 
Published: June 2021

Aerobic exercise has been known an effective therapy against the muscle endurance fitness. And skeletal muscle is classified into 2 types, slow or fast muscle. Slow muscles have rich oxidative utilization and rich capillaries. And rat soleus muscle is a slow muscle.PURPOSETo clarify the effect of aerobic training exercise on capillary architecture in slow muscle, the 3‐D capillarity has been investigated.METHODSWistar rat (Con) rats and age matched Wistar rat that performed aerobic exercise preconditioning for 3 weeks (EX) were used. Contrast medium‐injected capillary in soleus muscle was visualized using a confocal laser microscope. And vascular endothelial growth factor (VEGF) expression was measured.RESULTSVEGF expression in EX was significantly higher than that in Con. Number of capillaries and number of anastomoses in EX were increased than Con. Capillary diameter in soleus of EX rat was thicker than that of Con. And mean capillary volume in EX was significantly higher than that in Con.CONCLUSIONResults of present study indicate that aerobic training builds capillarity architecture in soleus muscle more closely. This study was supported by Grantsin‐ Aid for Scientific Research from the Japanese Ministry of Education, Culture, Sports, Science and Technology no. 23650340, 23650324, 23700600, 23700932 and 22300189.
Hypertension development in ethanol treated rats could involve baroreflex activity
Authors: da Silva Andreia Lopes , Crestani Carlos C , Scopinho America A , Correa Fernando MA , Elias Lucila LK , Antunes-Rodrigues Jose , Resstel Leonardo BM 
Published: June 2021

This study evaluated MAP, HR and baroreflex responses in unanesthetized male wistar rats maintained under ethanol treatment (1st: 5%, 2nd: 10%, 3rd and 4th: 20%). After this period water was replaced for one week. During the treatment rats had a progressive increase of MAP since the 1st week, without alteration of HR. This increase was sustained until the 4th week and returned to normal after withdrawal. The baroreflex analysis with linear regression indicated no difference between slopes of bradycardic and tachycardic responses on the 1st and 2nd weeks. However, after 3rd and 4th weeks it was observed alteration between slopes of bradycardic (3rd t=2.27, p<0.05; 4th t=4.76, p<0.01) and tachycardic responses (3rd t=2.41, p<0.05; 4th t=3.65, p<0.01). After withdrawal linear regression analysis indicated no difference between slopes of bradycardic and tachycardic responses. These results indicate that ethanol treatment promotes a mild hypertension being this effect dependent on ethanol consume. Moreover, the baroreflex analysis showed a possible increase of sympathetic activity after 3rd week, which could involve MAP increases in ethanol treated rats.Financial Support: FAPESP.
The effects of a 5 second bend over maneuver on cerebral perfusion and autoregulation upon standing from squat
Authors: Bentley Robert F , Walsh Jeremy J , Kellawan J Mikhail , Tschakovsky Michael E 
Published: June 2021

PURPOSETo investigate the effects of maintaining a bent over posture (BOP) for 5 s upon rising from squat on cerebral autoregulation.METHODS8 healthy subjects (24.4 ± 1.9 years) completed 1 min of quiet standing, followed by 1 min of squat, followed by rising from squat over a 1–2 s period and then no maneuver (CON) or a BOP maneuver for 5 s before standing upright. Middle cerebral artery blood velocity (MCABV (cm/s); Transcranial Doppler) and mean arterial blood pressure at heart level (MAP (mmHg); finger photoplethysmography) were continuously measured. Cerebral vascular conductance (CVC) was calculated from MCA blood pressure (MCABP) and MCABV. MCABP was estimated by accounting for the hydrostatic column between the heart and the MCA.RESULTSData are mean Δ from bsl ± SD. BOP attenuated the decrease in MCABV during the first 5 s upon rising from squat compared to CON (−6.5 ± 2.5 vs. −12.1 ± 3.1, P<0.05). MAP hypotension during the same time period was abolished in BOP (+3.8 ± 10.0 vs. −12.9 ± 4.5, P<0.05). Upon restoring upright posture in BOP, the MAP nadir ~10 s after rising was virtually identical but the drop in MCABV was attenuated in BOP, indicating CVC was functionally increased (+0.41 ± 0.3 vs. +0.2 ± 0.1, P=0.1).CONCLUSIONSThe BOP maneuver blunts disturbances to cerebral perfusion following rising from squat during the 5 s that it is maintained and enhances cerebral vasodilation at the MAP nadir after rising. NSERC.
Acute dietary nitrate consumption improves glucose tolerance
Authors: Scalzo Rebecca Lynn , Peltonen Garrett L. , Schweder Melani M. , Szaller Steve E. , Binns Scott E. , Wood Lacey M. , Klochak Anna L. , Bell Christopher 
Published: June 2021

Insulin resistance is characterized by low nitric oxide (NO) bioavailability. Consistent with this observation, insulin sensitivity is improved with stimulation of NO generating pathways. Consumption of dietary nitrate (e.g. beet juice) has been purported to increase NO formation, mediated in part through the reduction of nitrate (NO3−) to nitrite (NO2−) by oral bacteria, and subsequent NO2− reduction to NO in blood. We hypothesized that acute dietary nitrate consumption would improve glucose tolerance. Accordingly, in 8 sedentary adults (23 ± 0 years, body mass index: 26.0 ± 0.8 kg/m2 (mean ± SE)) we determined the blood glucose response to oral consumption of 500 ml organic beet juice, supplemented with 25 g of sucrose (estimated carbohydrate load ~ 75g), with and without prior use of an antibacterial mouthwash to inhibit NO3− reduction to NO2−. In the absence of inhibition of oral bacteria NO3− reductase activity, peak blood glucose concentration (106 ± 4 vs. 118 ± 6 mg/dL; P = 0.04) and the area under the blood glucose response curve (93 ± 4%; P = 0.07) were decreased. These preliminary data suggest dietary nitrate consumption may promote glucose tolerance, and this effect may be attenuated following inhibition of NO3− conversion to NO2−.Support: America Diabetes Association 1‐09‐RA‐09
Renal responses to severe haemorrhage in conscious lambs
Authors: Smith Francine Gabriel , Samhan Mohamed , Qi Wei 
Published: June 2021

The role of the kidney in the physiological responses to severe degrees of haemorrhage beyond which compensatory mechanisms fail (>25% of vascular volume) has not been investigated in the newborn period. In this study, parameters of glomerular and tubular function were measured for 30 min before (Control, C) and 120 min after haemorrhage of 30% of vascular volume, in conscious, chronically instrumented lambs aged ~one (N=10) and ~six weeks (N=9). Renal plasma flow decreased 30 min after haemorrhage from 1.4±0.5 SD (C) to 0.7±0.2 mL.min−1.g−1 at one week and from 1.6±0.4 (C) to 0.9±0.4 mL.min−1.g−1 at six weeks and remained decreased at 120 min. Similarly, glomerular filtration rate decreased from 0.26±0.08 (C) to 0.18±0.14 mL.min−1.g−1 at one week and from 0.31±0.08 (C) to 0.17±0.08 mL.min−1.g−1 at six weeks, and remained below C at 120 min. Urinary flow rate also decreased from 3.8±1.6 (C) to 1.8±0.7 uL.min−1.g−1 by 30 min after haemorrhage at one week and from 3.9±1.5 (C) to 2.2±0.8 uL.min−1.g−1 at six weeks, and remained below C at 120 min. Clearances of Na+ and K+ also decreased after haemorrhage in both age groups. These data provide evidence that soon after birth, glomerular and tubular responses to severe blood loss are elicited, though they do not appear to be developmentally regulated.[Supported by the Canadian Institutes of Health Research.]
Blood pressure and renal hemodynamics in hypertensive Cyp1a1‐Ren2 transgenic rats fed a sodium‐deficient diet
Authors: Collins Amy E , Howard Catherine G , Mitchell Kenneth D 
Published: June 2021

The present study was performed to determine whether dietary sodium restriction attenuates the development of hypertension and the impairment in renal hemodynamics that occur during the induction of the Ren2 gene in Cyp1a1‐Ren2 rats. Male Cyp1a1‐ Ren2 rats (n=5–6/group) were fed either a normal salt (0.6%) or salt‐deficient diet (<0.01%) containing indole‐3‐carbinol (I3C; 0.15%, wt/wt) for 16 days to induce slowly progressive ANG II‐dependent hypertension. The rats were then anesthetized with pentobarbital sodium and surgically prepared for measurement of mean arterial pressure (MAP), renal hemodynamics and renal excretory function. There were no significant differences between the induced normal salt group and the induced salt‐deficient group regarding MAP (183±4 vs. 181±5 mmHg), RVR (33.7±2.4 vs. 31.1±3.8 mmHg/mL/min.g), RPF (2.78±0.20 vs. 2.91±0.35 mL/min.g), or GFR (0.90±0.06 vs. 0.91±0.08 mL/min.g). Both groups had similar urine flows (41.1±1.3 vs. 39.0±6.9 μL/min), urinary sodium excretions (2.9±0.5 vs. 2.4±0.9 μEq/min) and fractional sodium excretions (0.94±0.15 vs. 0.76±0.22%). These data demonstrate that a sodium‐deficient diet does not attenuate the increase in arterial blood pressure or the associated renal functional derangements in Cyp1a1‐Ren2 transgenic rats with slowly progressive ANG II‐dependent hypertension.Support: NHLBI, Tulane COBRE in Hypertension and Renal Biology.