scholarly journals Hypoxia Inducible Factor-2α Is Translationally Repressed in Response to Dietary Iron Deficiency in Sprague-Dawley Rats

2011 ◽  
Vol 141 (9) ◽  
pp. 1590-1596 ◽  
Author(s):  
McKale R. Davis ◽  
Krista M. Shawron ◽  
Elizabeth Rendina ◽  
Sandra K. Peterson ◽  
Edralin A. Lucas ◽  
...  
Keyword(s):  
Iron Deficiency ◽  
Hypoxia Inducible Factor ◽  
Dietary Iron ◽  
Sprague Dawley ◽  
Sprague Dawley Rats

Lactate is essential for maintenance of euglycemia in iron-deficient rats at rest and during exercise

1993 ◽  
Vol 264 (4) ◽  
pp. E662-E667 ◽  
Author(s):  
J. K. Linderman ◽  
P. R. Dallman ◽  
R. E. Rodriguez ◽  
G. A. Brooks
Keyword(s):  
Iron Deficiency ◽  
Hemoglobin Concentration ◽  
Liver Glycogen ◽  
Beta Blockade ◽  
Sprague Dawley ◽  
Sprague Dawley Rats ◽  
Iron Deficient ◽  
Ici 118,551 ◽  
Beta 2 ◽  
Exercise Induced

To evaluate the hypothesis that lactate supply is essential to maintain euglycemia during iron deficiency, female Sprague-Dawley rats were assigned to iron-sufficient (50 mg Fe2+/kg diet, +Fe), or iron-deficient (15 mg Fe2+/kg diet, -Fe) dietary groups and were injected with a specific beta 2-adrenergic inhibitor, ICI 118,551 (1.0 mg/kg body wt). Rats were studied at rest or after 30 min of running at 13.4 m/min 0% grade. Dietary iron deficiency decreased hemoglobin concentration 38%, but resting arterial concentrations of glucose ([Glc]), lactate ([La]), or alanine ([Ala]) were unaffected. Administration of ICI 118,551 (beta 2-blockade) decreased [La] and [Glc] 52 and 32% in resting -Fe rats, respectively. beta 2-Blockade attenuated the exercise-induced rise in [La] and decreased [Glc] 31% in exercising -Fe rats. [Ala] were unaffected by iron deficiency or exercise but decreased 24 and 18% because of beta 2-blockade in resting and exercising +Fe rats. Iron deficiency depleted resting liver glycogen concentration 45%, with no additional effect of exercise or beta 2-blockade. beta-Blockade decreased arterial insulin and increased arterial glucagon concentrations in resting -Fe and +Fe rats. During exercise glucagon concentration increased significantly more in -Fe than +Fe rats. Decreased arterial [La] with a corresponding decrease in arterial [Glc] in response to beta 2-blockade support the contention that lactate supply is critical to maintenance of euglycemia in -Fe rats at rest and during exercise.

scholarly journals Iron deficiency alters dopamine uptake and response to L-DOPA injection in Sprague–Dawley rats

2008 ◽  
Vol 106 (1) ◽  
pp. 205-215 ◽  
Author(s):  
Laura E. Bianco ◽  
Jason Wiesinger ◽  
Christopher J. Earley ◽  
Byron C. Jones ◽  
John L. Beard
Keyword(s):  
Iron Deficiency ◽  
Dopamine Uptake ◽  
Sprague Dawley ◽  
Sprague Dawley Rats

scholarly journals The mTORC1/eIF4E/HIF-1α Pathway Mediates Glycolysis to Support Brain Hypoxia Resistance in the Gansu Zokor, Eospalax cansus

2021 ◽  
Vol 12 ◽  
Author(s):  
Jinyan Lin ◽  
Lele Fan ◽  
Yuming Han ◽  
Juanjuan Guo ◽  
Zhiqiang Hao ◽  
...  
Keyword(s):  
Hypoxia Inducible Factor ◽  
Eukaryotic Cell ◽  
Metabolic Energy ◽  
Subterranean Rodents ◽  
Sprague Dawley ◽  
Subterranean Rodent ◽  
Downstream Targets ◽  
Metabolic Characteristics ◽  
Hypoxic Conditions ◽  
Sprague Dawley Rats

The Gansu zokor (Eospalax cansus) is a subterranean rodent species that is unique to China. These creatures inhabit underground burrows with a hypoxia environment. Metabolic energy patterns in subterranean rodents have become a recent focus of research; however, little is known about brain energy metabolism under conditions of hypoxia in this species. The mammalian (mechanistic) target of rapamycin complex 1 (mTORC1) coordinates eukaryotic cell growth and metabolism, and its downstream targets regulate hypoxia inducible factor-1α (HIF-1α) under conditions of hypoxia to induce glycolysis. In this study, we compared the metabolic characteristics of hypoxia-tolerant subterranean Gansu zokors under hypoxic conditions with those of hypoxia-intolerant Sprague-Dawley rats with a similar-sized surface area. We exposed Gansu zokors and rats to hypoxia I (44 h at 10.5% O2) or hypoxia II (6 h at 6.5% O2) and then measured the transcriptional levels of mTORC1 downstream targets, the transcriptional and translational levels of glycolysis-related genes, glucose and fructose levels in plasma and brain, and the activity of key glycolysis-associated enzymes. Under hypoxia, we found that hif-1α transcription was upregulated via the mTORC1/eIF4E pathway to drive glycolysis. Furthermore, Gansu zokor brain exhibited enhanced fructose-driven glycolysis under hypoxia through increased expression of the GLUT5 fructose transporter and ketohexokinase (KHK), in addition to increased KHK enzymatic activity, and utilization of fructose; these changes did not occur in rat. However, glucose-driven glycolysis was enhanced in both Gansu zokor and rat under hypoxia II of 6.5% O2 for 6 h. Overall, our results indicate that on the basis of glucose as the main metabolic substrate, fructose is used to accelerate the supply of energy in Gansu zokor, which mirrors the metabolic responses to hypoxia in this species.

scholarly journals Shaofu Zhuyu Decoction Regresses Endometriotic Lesions in a Rat Model

2018 ◽  
Vol 2018 ◽  
pp. 1-7 ◽  
Author(s):  
Guanghui Zhu ◽  
Chunhua Jiang ◽  
Xin Yan ◽  
Shu Zhao ◽  
Dingjie Xu ◽  
...  
Keyword(s):  
Rat Model ◽  
Hypoxia Inducible Factor ◽  
Nuclear Antigen ◽  
Terminal Deoxynucleotidyl Transferase ◽  
Sprague Dawley ◽  
Estrous Cycles ◽  
Treatment And Prevention ◽  
Sprague Dawley Rats ◽  
Current Therapies ◽  
Ectopic Endometrium

The current therapies for endometriosis are restricted by various side effects and treatment outcome has been less than satisfactory. Shaofu Zhuyu Decoction (SZD), a classic traditional Chinese medicinal (TCM) prescription for dysmenorrhea, has been widely used in clinical practice by TCM doctors to relieve symptoms of endometriosis. The present study aimed to investigate the effects of SZD on a rat model of endometriosis. Forty-eight female Sprague-Dawley rats with regular estrous cycles went through autotransplantation operation to establish endometriosis model. Then 38 rats with successful ectopic implants were randomized into two groups: vehicle- and SZD-treated groups. The latter were administered SZD through oral gavage for 4 weeks. By the end of the treatment period, the volume of the endometriotic lesions was measured, the histopathological properties of the ectopic endometrium were evaluated, and levels of proliferating cell nuclear antigen (PCNA), CD34, and hypoxia inducible factor- (HIF-) 1α in the ectopic endometrium were detected with immunohistochemistry. Furthermore, apoptosis was assessed using the terminal deoxynucleotidyl transferase (TdT) deoxyuridine 5′-triphosphate (dUTP) nick-end labeling (TUNEL) assay. In this study, SZD significantly reduced the size of ectopic lesions in rats with endometriosis, inhibited cell proliferation, increased cell apoptosis, and reduced microvessel density and HIF-1α expression. It suggested that SZD could be an effective therapy for the treatment and prevention of endometriosis recurrence.

Reciprocal changes of muscle oxidases and liver enzymes with recovery from iron deficiency

1989 ◽  
Vol 256 (3) ◽  
pp. E401-E405
Author(s):  
J. L. Azevedo ◽  
W. T. Willis ◽  
L. P. Turcotte ◽  
A. S. Rovner ◽  
P. R. Dallman ◽  
...  
Keyword(s):  
Iron Deficiency ◽  
Liver Enzymes ◽  
Hemoglobin Concentration ◽  
Glycolytic Enzyme ◽  
Sprague Dawley ◽  
Tissue Samples ◽  
Iron Administration ◽  
Sprague Dawley Rats ◽  
Iron Deficient ◽  
Time Courses

We determined the recovery time courses of muscle oxidases and liver enzymes after iron administration to iron-deficient rats. Female 21-day-old Sprague-Dawley rats were fed an iron-deficient (3 mg Fe/kg) or a control (50 mg Fe/kg) diet for 3 wk. The deficient rats were then injected with 50 mg Fe as iron dextran/kg body wt (Fe-T) or saline (Fe-) intraperitoneally. At 16, 40, 64, 112, and 180 h after injection, blood and tissue samples were taken to determine hemoglobin concentration (Hb), gastrocnemius glycolytic enzyme and oxidase activities, and liver amino acid catabolic enzyme activities. No changes were observed in any parameter across time in either the Fe- or control (Fe+) rats. In the Fe- rats, Hb, pyruvate + malate (P + M), 2-oxoglutarate (2-OG), and succinate oxidases (SO) were depressed to 33, 36, 44, and 7% of Fe+, respectively (P less than 0.05). At 16 h, Fe-T values were significantly elevated compared with Fe- rats but still only 40, 48, 55 and 10% of controls, respectively. Glutamate dehydrogenase (GDH) and alanine aminotransferase (AAT) of Fe- rats were 174 and 134% of control values (P less than 0.05). By the 180-h time point, Hb, P + M, 2-OG, and SO of Fe-T rats increased to 99, 84, 89, and 43% of Fe+ values, whereas GDH and AAT activities declined to 111 and 106% of controls. Glycolytic enzymes showed no systematic changes with iron deficiency or after iron administration.(ABSTRACT TRUNCATED AT 250 WORDS)

scholarly journals Perturbed Vitamin A Status Induced by Iron Deficiency Is Corrected by Iron Repletion in Rats with Pre-Existing Iron Deficiency

2020 ◽  
Vol 150 (7) ◽  
pp. 1989-1995
Author(s):  
Yaqi Li ◽  
Cheng-Hsin Wei ◽  
Xia Xiao ◽  
Michael H Green ◽  
A Catharine Ross
Keyword(s):  
Iron Deficiency ◽  
Vitamin A ◽  
Kinetic Studies ◽  
Inhibitory Effect ◽  
Control Group ◽  
Sprague Dawley ◽  
Vitamin A Status ◽  
Sprague Dawley Rats ◽  
Iron Deficient ◽  
Plasma Retinol

ABSTRACT Background Although iron deficiency is known to interrupt vitamin A (VA) metabolism, the ability of iron repletion to restore VA metabolism and kinetics in iron-deficient rats is not well understood. Objectives In the present study, we examined the effects of dietary iron repletion on VA status in rats with pre-existing iron deficiency. Methods Weanling Sprague-Dawley rats were fed a VA-marginal diet (0.35 mg retinol/kg diet) containing either a normal concentration of iron [35 ppm, control group (CN)] or reduced iron (3 ppm, iron-deficient group, ID−); after 5 wk, 4 rats/group were killed for baseline measurements. A 3H-labeled retinol emulsion was administered intravenously to the remaining rats (n = 6, CN; n = 10, ID−) as tracer to initiate the kinetic study. On day 21 after dosing, n = 5 ID− rats were switched to the CN diet, generating an iron-repletion group (ID+). Blood samples were collected at 34 time points ≤92 d after dose administration, when all rats were killed and iron and VA status were determined. Results At baseline, ID− rats had developed iron deficiency, with a reduced plasma VA concentration (0.67 compared with 1.20 μmol/L in ID− and CN rats, respectively; P < 0.01) and a tendency toward higher liver VA (265 compared with 187 nmol in ID− and CN rats, respectively; P = 0.10). On day 92, iron deficiency persisted in ID− rats, accompanied by 2-times higher liver VA (456 nmol compared with 190 nmol in ID− and CN rats, respectively; P < 0.001) but lower plasma VA (0.64 compared with 0.94 μmol/L in ID− and CN rats, respectively; P = 0.05). ID+ rats not only recovered from iron deficiency, but also exhibited less liver VA sequestration (276 nmol) and normal plasma VA (0.91 μmol/L, not different from CN rats). Conclusions Our results suggest that iron repletion can remove the inhibitory effect of iron deficiency on hepatic mobilization of VA and restore plasma retinol concentrations in iron-deficient rats, setting the stage for kinetic studies of VA turnover in this setting.

FINASTERIDE INDUCES HYPOXIA-INDUCIBLE FACTOR 1-ALPHA IN THE PROSTATE OF SPRAGUE-DAWLEY RATS

2009 ◽  
Vol 181 (4S) ◽  
pp. 95-95
Author(s):  
Janmejai K Srivastava ◽  
Sanjeev Shukla ◽  
Cherry Kamel ◽  
Gregory T MacLennan ◽  
Allen D Seftel ◽  
...  
Keyword(s):  
Hypoxia Inducible Factor ◽  
Sprague Dawley ◽  
Hypoxia Inducible Factor 1 ◽  
Sprague Dawley Rats

scholarly journals Perinatal Iron Deficiency Combined with a High-Fat Diet Causes Obesity and Cardiovascular Dysregulation

Endocrinology ◽  
2012 ◽  
Vol 153 (3) ◽  
pp. 1174-1182 ◽  
Author(s):  
Stephane L. Bourque ◽  
Marina Komolova ◽  
Kristin McCabe ◽  
Michael A. Adams ◽  
Kanji Nakatsu
Keyword(s):  
Adipose Tissue ◽  
Locomotor Activity ◽  
Iron Deficiency ◽  
Visceral Adipose Tissue ◽  
Caloric Intake ◽  
Normal Diet ◽  
Sprague Dawley ◽  
High Fat ◽  
Sprague Dawley Rats ◽  
Visceral Adipose

Consumption of a high-fat Western diet (WD) and the resultant obesity is linked to a number of chronic pathologies, including cardiovascular dysregulation. The purpose of the present study was to determine whether perinatal iron deficiency (PID) added to the consumption of a WD would precipitate an obese phenotype with exacerbated metabolic and cardiovascular outcomes in adult offspring. Female Sprague Dawley rats were fed either a control (225 mg/kg Fe) or an iron-restricted diet (3–10 mg/kg Fe) prior to and throughout gestation. At birth, all dams were fed an iron-replete diet. At weaning, offspring were fed a normal diet or WD for up to 21 wk. Hemodynamics and locomotor activity were assessed by radiotelemetry starting at 15 wk of age. Iron restriction during pregnancy caused severe anemia in dams and offspring, resulting in 15% lower birth weights in the offspring. PID offspring fed the WD had greater caloric intake and exhibited reduced locomotor activity compared with their normal diet-fed littermates; no such effects were observed in normal iron control offspring. Despite having a similar effect on serum lipid profiles, consumption of the WD had a greater impact on body weight in the PID group, and this weight gain was due largely to visceral adipose tissue accumulation. A significant correlation between visceral adipose tissue weight and mean arterial pressure was observed in the PID offspring but not in controls. These observations demonstrate that PID predisposes offspring to an enhanced response to WD characterized by increased fat accumulation and cardiovascular dysregulation.

scholarly journals Evaluation of the Carcinogenic Potential of Roxadustat (FG-4592), a Small Molecule Inhibitor of Hypoxia-Inducible Factor Prolyl Hydroxylase in CD-1 Mice and Sprague Dawley Rats

2017 ◽  
Vol 36 (6) ◽  
pp. 427-439 ◽  
Author(s):  
James Beck ◽  
Carroll Henschel ◽  
James Chou ◽  
Al Lin ◽  
Ughetta del Balzo
Keyword(s):  
Small Molecule ◽  
Hypoxia Inducible Factor ◽  
Small Molecule Inhibitor ◽  
Prolyl Hydroxylase ◽  
Sprague Dawley ◽  
Oral Gavage ◽  
Distribution Width ◽  
Sprague Dawley Rats ◽  
Molecule Inhibitor ◽  
Carcinogenic Potential

The carcinogenic potential of roxadustat (FG-4592), a novel orally active, heterocyclic small molecule inhibitor of hypoxia-inducible factor prolyl hydroxylase (HIF-PH) enzymes in clinical development for treatment of anemia, was evaluated in CD-1 mice and Sprague Dawley rats. Inhibition of HIF-PH by roxadustat leads to a rapid increase in cytoplasmic HIF-α concentrations, followed by translocation of HIF-α to the nucleus and upregulation of HIF-responsive genes, including erythropoietin. Roxadustat was dosed by oral gavage 3 times weekly (TIW) for up to 104 weeks in mice at 0, 15, 30, and 60 mg/kg and in rats at 0, 2.5, 5, and 10 mg/kg. Treatment-associated changes in hematology parameters were consistent with the pharmacologic activity of roxadustat and included elevations in hematocrit in mice at 30 and 60 mg/kg TIW and elevations in erythrocyte count, hemoglobin, hematocrit, and red cell distribution width in rats at 10 mg/kg TIW. No increase in mortality or neoplastic effects compared with vehicle controls was observed after roxadustat treatment in either species. No treatment-related nonneoplastic findings were observed in mice, whereas nonneoplastic microscopic findings in rats were limited to atrial/aortic thromboses at 10 mg/kg TIW males and bone marrow hypercellularity in all treated male and female groups, consistent with the pharmacology of roxadustat. In conclusion, roxadustat administered by oral gavage to mice and rats TIW for up to 104 weeks resulted in dose-dependent exposure and hematologic effects with no effect on survival or development of neoplastic lesions at up to 60 mg/kg in mice and up to 10 mg/kg in rats.

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