Exogenous Ketone Ester Delays CNS Oxygen Toxicity Without Impairing Cognitive and Motor Performance in Male Sprague Dawley Rats

2021 ◽  
Author(s):  
Nicole M Stavitzski ◽  
Carol S. Landon ◽  
Christopher M. Hinojo ◽  
Angela M. Poff ◽  
Christopher Q. Rogers ◽  
...  
Keyword(s):  
Motor Performance ◽  
Oxygen Toxicity ◽  
Anxiolytic Effect ◽  
Optimal Dose ◽  
Male Rats ◽  
Sprague Dawley ◽  
Oral Gavage ◽  
Sprague Dawley Rats ◽  
And Performance ◽  
Ketone Ester

Hyperbaric oxygen (HBO2) is breathing greater than 1 ATA (101.3 kPa) O2 and is used in HBO2 therapy and undersea medicine. What limits the use of HBO2 is the risk of developing CNS oxygen toxicity (CNS-OT). A promising therapy for delaying CNS-OT is ketone metabolic therapy either through diet or exogenous ketone ester (KE) supplement. Previous studies indicate that KE induces ketosis and delays the onset of CNS-OT; however, the effects of exogeneous KE on cognition and performance are understudied. Accordingly, we tested the hypothesis that oral gavage with 7.5 g/kg induces ketosis and increases the latency time to seizure (LSz) without impairing cognition and performance. A single oral dose of 7.5 g/kg KE increases systemic b-hydroxybutyrate (BHB) levels within 0.5 hr and remains elevated for 4 hr. Male rats were separated into 3 groups: control (no gavage), water-gavage, or KE-gavage; and were subjected to behavioral testing while breathing 1 ATA (101.3 kPa) air. Testing included the following: DigiGait (DG), Light/Dark (LD), open field (OF), and novel object recognition (NOR). There were no adverse effects of KE on gait or motor performance (DG), cognition (NOR), and anxiety (LD, OF). In fact, KE had an anxiolytic effect (OF, LD). The LSz during exposure to 5 ATA (506.6 kPa) O2 (£90 min) increased 307% in KE-treated rats compared to control rats. In addition, KE prevented seizures in some animals. We conclude that 7.5 g/kg is an optimal dose of KE in the male Sprague-Dawley rat model of CNS-OT.

Ketone Ester Supplementation Does Not Impair Cognitive or Motor Performance and Delays CNS Oxygen Toxicity in Male Sprague‐Dawley Rats

2020 ◽  
Vol 34 (S1) ◽  
pp. 1-1
Author(s):  
Nicole M. Stavtizski ◽  
Carol S. Landon ◽  
Christopher M. Hinojo ◽  
Angela M. Poff ◽  
Christopher Q. Rogers ◽  
...  
Keyword(s):  
Motor Performance ◽  
Oxygen Toxicity ◽  
Sprague Dawley ◽  
Sprague Dawley Rats ◽  
Ketone Ester

scholarly journals Early Occurrence of Spontaneous Tumors in CD-1 Mice and Sprague—Dawley Rats

2004 ◽  
Vol 32 (4) ◽  
pp. 371-374 ◽  
Author(s):  
Woo-Chan Son ◽  
Chirukandath Gopinath
Keyword(s):  
Life Sciences ◽  
Male Rats ◽  
Sprague Dawley ◽  
Control Groups ◽  
Oral Gavage ◽  
Short Term ◽  
Young Control ◽  
Sprague Dawley Rats ◽  
Early Occurrence ◽  
General Profile

It is sometimes difficult to assess the relevance of tumors that occur in treated animals in short-term studies. This report is intended to establish a general profile of tumor occurrence in young control CD-1 mice and Sprague—Dawley rats. Data from 20 rat and 20 mouse carcinogenicity studies conducted between 1990 and 2002 at Huntingdon Life Sciences, UK, were collected and evaluated. The route of administration was either dietary or oral gavage, and the analysis was confined to sporadic deaths (decedents) in control groups occurring during the first 50 weeks of study. In addition, tumor occurrence between 50—80 weeks were compared. In mice, the most common tumor was lymphoma, followed by bronchiolo-alveolar adenoma. In rats, the most common tumor was adenoma of the pituitary gland, followed by mammary fibroadenoma, and adenocarcinoma. When studies of up to 50 weeks, between 50 and 80 weeks, and at 2-year termination were compared, there was no great difference in tumor occurrence except in male rats, in which the most common tumor up to 50 weeks on study was lymphoma, whereas the most common tumor between 50—80 weeks and at 2 years was pituitary adenoma.

Toxicokinetic and Genotoxicity Study of NNK in Male Sprague-Dawley Rats Following Nose-Only Inhalation Exposure, Intraperitoneal Injection, and Oral Gavage

2021 ◽  
Author(s):  
Shu-Chieh Hu ◽  
Matthew S Bryant ◽  
Estatira Sepehr ◽  
Hyun-Ki Kang ◽  
Raul Trbojevich ◽  
...  
Keyword(s):  
Human Lung ◽  
Inhalation Exposure ◽  
Systemic Exposure ◽  
Sprague Dawley ◽  
Oral Gavage ◽  
Sd Rats ◽  
New Information ◽  
Sprague Dawley Rats ◽  
Tissue Specimens

Abstract The tobacco-specific nitrosamine NNK [4-(methylnitrosamino)-1-(3-pyridyl)-1-butanone] is found in tobacco products and tobacco smoke. NNK is a potent genotoxin and human lung carcinogen; however, there are limited inhalation data for the toxicokinetics (TK) and genotoxicity of NNK in vivo. In the present study, a single dose of 5x10−5, 5x10−3, 0.1, or 50 mg/kg body weight (BW) of NNK, 75% propylene glycol (vehicle control), or air (sham control) was administered to male Sprague-Dawley (SD) rats (9-10 weeks age) via nose-only inhalation (INH) exposure for 1 hour. For comparison, the same doses of NNK were administered to male SD rats via intraperitoneal (IP) injection and oral gavage (PO). Plasma, urine, and tissue specimens were collected at designated timepoints and analyzed for levels of NNK and its major metabolite 4-(methylnitrosamino)-1-(3-pyridyl)-1-butanol (NNAL) and tissue levels of DNA adduct O6-methylguanine by LC/MS/MS. TK data analysis was performed using a non-linear regression program. For the genotoxicity subgroup, tissues were collected at 3 hours post-dosing for comet assay analysis. Overall, the TK data indicated that NNK was rapidly absorbed and metabolized extensively to NNAL after NNK administration via the three routes. The IP route had the greatest systemic exposure to NNK. NNK metabolism to NNAL appeared to be more efficient via INH than IP or PO. NNK induced significant increases in DNA damage in multiple tissues via the three routes. The results of this study provide new information and understanding of the toxicokinetics and genotoxicity of NNK.

scholarly journals Erythropoietin Produces a Dual Effect on Carotid Body Chemoreception in Male Rats

2021 ◽  
Vol 12 ◽  
Author(s):  
Christian Arias-Reyes ◽  
Sofien Laouafa ◽  
Natalia Zubieta-DeUrioste ◽  
Vincent Joseph ◽  
Aida Bairam ◽  
...  
Keyword(s):  
Carotid Body ◽  
No Synthase ◽  
Male Rats ◽  
High Dose ◽  
No Production ◽  
Sprague Dawley ◽  
En Bloc ◽  
No Synthase Inhibitor ◽  
Sprague Dawley Rats ◽  
Synthase Inhibitor

Erythropoietin (EPO) regulates respiration under conditions of normoxia and hypoxia through interaction with the respiratory centers of the brainstem. Here we investigate the dose-dependent impact of EPO in the CB response to hypoxia and hypercapnia. We show, in isolated “en bloc” carotid body (CB) preparations containing the carotid sinus nerve (CSN) from adult male Sprague Dawley rats, that EPO acts as a stimulator of CSN activity in response to hypoxia at concentrations below 0.5 IU/ml. Under hypercapnic conditions, EPO did not influence the CSN response. EPO concentrations above 0.5 IU/ml decreased the response of the CSN to both hypoxia and hypercapnia, reaching complete inhibition at 2 IU/ml. The inhibitory action of high-dose EPO on the CSN activity might result from an increase in nitric oxide (NO) production. Accordingly, CB preparations were incubated with 2 IU/ml EPO and the unspecific NO synthase inhibitor (L-NAME), or the neuronal-specific NO synthase inhibitor (7NI). Both NO inhibitors fully restored the CSN activity in response to hypoxia and hypercapnia in presence of EPO. Our results show that EPO activates the CB response to hypoxia when its concentration does not exceed the threshold at which NO inhibitors masks EPO’s action.

Effects of androgens on bioactivity and immunoreactivity of pituitary FSH in GnRH antagonist-treated male rats

1990 ◽  
Vol 122 (2) ◽  
pp. 168-174 ◽  
Author(s):  
Om P. Sharma ◽  
Shafiq A. Khan ◽  
Gerhard F. Weinbauer ◽  
Mohammed Arslan ◽  
Eberhard Nieschlag
Keyword(s):  
Isoelectric Focusing ◽  
Gnrh Antagonist ◽  
Molecular Composition ◽  
Male Rats ◽  
Sprague Dawley ◽  
Sprague Dawley Rats ◽  
Combined Administration ◽  
Ph Range ◽  
Fsh Bioactivity

Abstract The effects of androgens on the bioactivity and molecular composition of pituitary FSH were examined in intact and GnRH antagonist-suppressed male rats. Eight groups of adult Sprague-Dawley rats were subjected to the following treatments: antagonist (75 μg/day by osmotic minipumps; sc), testosterone-filled Silastic implants (3×5 cm, sc), dihydrotestosterone-filled Silastic implants (3×5 cm, sc), E2 benzoate (15 μg/day, sc), and combined administration of antagonist with either steroid for 3 weeks. At the end of the treatment period, pituitaries were dissected out and homogenised. FSH content was determined in the pituitary extracts by an in vitro bioassay and a radioimmunoassay. Individual pituitary extracts from rats treated with vehicle, testosterone and testosterone + antagonist were subjected to isoelectric-focusing on sucrose density gradients performed in the pH range from 3.5 to 7.0. Individual isoelectric-focusing fractions (100-120) were analysed for bioactive and immunoreactive FSH. Treatment with antagonist, E2 or antagonist + E2 caused a significant decrease in pituitary FSH, whereas testosterone and dihydrotesterone alone or in combination with antagonist prevented the decrease in pituitary FSH. The effects of all treatments on both bioactive and immunoreactive FSH were similar. Testosterone treatment not only maintained FSH synthesis but also altered the molecular composition of pituitary FSH. Following treatment with testosterone there was a shift of maximal FSH bioactivity to the more acidic pH range. On the other hand, less bioactivity was recovered than corresponding immunoreactivity in the higher pH region, resulting in significantly reduced ratios of bioactivity to immunoreactivity of FSH. No significant differences were found in the isoelectric-focusing profiles or bioactivity to immunoreactivity ratios of pituitary FSH in animals treated with testosterone alone or in combination with antagonist. The results demonstrate that testosterone not only maintained the synthesis of both bioactive and immunoreactive FSH in male rats, but also influences the molecular composition of pituitary FSH. These effects of testosterone on pituitary FSH appear not to be mediated through hypothalamic GnRH.

Repeated restraint stress upregulates rat sulfotransferase 1A1

2018 ◽  
Vol 30 (2) ◽  
pp. 265-273
Author(s):  
Rajiv Balyan ◽  
Ma Cai ◽  
Wenhong Zhao ◽  
Zhao Dai ◽  
Yujia Zhai ◽  
...  
Keyword(s):  
Restraint Stress ◽  
Biological Activities ◽  
Male Rats ◽  
Transcriptional Level ◽  
Sprague Dawley ◽  
Metabolizing Enzymes ◽  
Sprague Dawley Rats ◽  
Repeated Restraint Stress ◽  
Enhanced Expression ◽  
Hormone Homeostasis

Abstract BackgroundSulfotransferases (SULTs) are phase II drug-metabolizing enzymes. SULTs also regulate the biological activities of biological signaling molecules, such as various hormones, bile acids, and monoamine neurotransmitters; therefore, they play critical roles in the endocrine and nervous systems. People are subject to various kinds of physical, chemical, toxicological, physiological, and psychological stresses at one time or another. The study of the effects produced by stress may lead to finding novel remedies for many disease conditions. The effect of repeated restraint stress on rat SULT expression has not been studied. MethodsThis study involves the effect of repeated restraint stress on SULT1A1 expressions. Male Sprague-Dawley rats (n=4) were subjected to repeated restraint stress 2 h/day for 7 days. Protein and RNA expression of SULT1A1 were analyzed by western blot and quantitative real time reverse transcription polymerase chain reaction, respectively, in important tissues. ResultsWe observed that repeated restraint stress increased the expression of SULT1A1 in the liver, adrenal glands, cerebellum, hypothalamus, and cerebral cortex in male rats. Patterns of enhanced expression were observed at both mRNA and protein level, indicating that repeated restraint stress stimulates enzyme expression at the transcriptional level. ConclusionsChanges of SULT1A1 expression in important tissues caused by repeated restraint stress will have a significant effect on drug metabolism and xenobiotics detoxification. The significant changes in endocrine glands and brain sections may also cause disturbances in hormone homeostasis, therefore leading to disease conditions. This report provides clues for the understanding of the effect of stresses on health.

scholarly journals THE EFFECT OF SECANG EXTRACT (CAESALPINIA SAPPAN LINN) ON THE WEIGHT AND HISTOLOGY APPEARANCE OF WHITE MALE RATS’ HEARTS INDUCED BY ISOPROTERENOL

2017 ◽  
Vol 9 ◽  
pp. 59
Author(s):  
Kristiana Nugraheni ◽  
Fadlina Chany Saputri
Keyword(s):  
Myocardial Infarction ◽  
Body Weight ◽  
White Male ◽  
Negative Control ◽  
Male Rats ◽  
Heart Cells ◽  
Sprague Dawley ◽  
Macroscopic Appearance ◽  
Caesalpinia Sappan ◽  
Sprague Dawley Rats

Objective: This study was conducted to determine the cardioprotective effect of secang extract on the heart cells of rats who suffered from myocardialinfarction induced by isoproterenol.Materials and Methods: Sprague Dawley rats were divided into six groups: Normal control, negative control, control extract (200 mg/kg), and threedifferent dose extract groups (50, 100, and 200 mg/kg body weight) that were given treatment for 30 days, and then, induced with isoproterenol.Observations were made for changes in the macroscopic appearance, cardiac weight, and histology of the cardiac organ.Results: The results showed a decrease in the incidence of myocardial infarction in rats given secang extract. The infarction area decreased withincreasing doses of extract. The weight of the heart in the control extract group was smaller than in the negative control group.Conclusions: Damage to heart cells, seen in the microscope, decreased with increasing doses.

scholarly journals Effects of Xuesaitong on the Pharmacokinetics of Losartan: An In Vivo UPLC-MS/MS Study

2019 ◽  
Vol 2019 ◽  
pp. 1-8
Author(s):  
Weina Ma ◽  
Lei Lv ◽  
Jungang Guo ◽  
Yongjun Meng ◽  
Yinghua Wang ◽  
...  
Keyword(s):  
Apparent Volume ◽  
Volume Of Distribution ◽  
Sprague Dawley ◽  
Oral Gavage ◽  
Sprague Dawley Rats ◽  
Liquid Chromatography Tandem Mass ◽  
Multiple Blood ◽  
Apparent Volume Of Distribution ◽  
Noncompartmental Model

The aim of this study was to examine whether Xuesaitong, a multiherbal formulation for coronary heart disease, alters the pharmacokinetics of losartan. Adult male Sprague Dawley rats randomly received losartan (10 mg/kg) or losartan plus Xuesaitong (10 mg/kg) through an oral gavage (n = 6). Multiple blood samples were obtained for up to 36 h to determine the concentrations of losartan and its active metabolite, EXP3174, through ultraperformance liquid chromatography-tandem mass spectrometry (UPLC-MS/MS). Pharmacokinetics were estimated using a noncompartmental model. The half-life (t1/2) of losartan was decreased by Xuesaitong (4.26 ± 1.51 vs. 6.35 ± 2.10 h; P<0.05). The apparent volume of distribution (Vd) of losartan was also decreased by the combination of losartan and Xuesaitong (4.41 ± 1.61 vs. 7.20 ± 2.41 mL; P<0.05). The time to maximum concentration (Tmax) of losartan was increased by Xuesaitong (1.06 ± 1.04 vs. 0.13 ± 0.05 h; P<0.05). Xuesaitong also decreased the t1/2 of EXP3174 (8.22 ± 1.41 vs. 6.29 ± 1.38 h; P<0.05). These results suggest that there is a complex interaction between losartan and Xuesaitong. In addition to enhanced elimination of losartan and EXP3174, Xuesaitong may also decrease the absorption rate and Vd of losartan.

Sexual dimorphism in vasopressin-induced contraction of rat aorta

1991 ◽  
Vol 260 (2) ◽  
pp. H453-H458 ◽  
Author(s):  
J. N. Stallone ◽  
J. T. Crofton ◽  
L. Share
Keyword(s):  
Estrous Cycle ◽  
Vascular Reactivity ◽  
Rat Aorta ◽  
Isometric Tension ◽  
Female Rats ◽  
Male Rats ◽  
Maximal Response ◽  
Sprague Dawley ◽  
Tension Development ◽  
Sprague Dawley Rats

Previously, we reported that, in the rat, pressor responsiveness to vasopressin (VP) is higher in males than in females during most phases of the estrous cycle. To explore the role of the vasculature in this phenomenon, we examined vascular reactivity to VP in thoracic aortas of male rats and female rats during each phase of the estrous cycle. Aortic rings were prepared from age-matched male and female Sprague-Dawley rats and mounted for isometric tension recording. Maximal response of female aortas to VP (4,246 +/- 163 mg/mg ring dry wt) was more than twice (P less than 0.001) that of male aortas (1,877 +/- 215 mg/mg ring wt). Sensitivity of female aortas to VP was substantially higher (P less than 0.001) than that of male aortas (EC50: 10.9 +/- 0.7 vs. 19.0 +/- 1.6 nM, respectively). Maximal rate of tension development (dT/dtmax) during contraction with VP was nearly twofold higher (P less than 0.01) in female aortas (536 +/- 23 mg/min) than in male aortas (300 +/- 19 mg/min). Maximal response, sensitivity, and dT/dtmax of female aortas did not vary significantly during the estrous cycle. Maximal response of female aortas to phenylephrine (PE; 1,251 +/- 93 mg/mg ring wt) was half that (P less than 0.001) of male aortas (2,546 +/- 194 mg/mg ring wt); sensitivity to PE did not differ significantly (EC50: 0.33 +/- 0.02 vs. 0.38 +/- 0.06 microM, respectively).(ABSTRACT TRUNCATED AT 250 WORDS)

scholarly journals Developmental Profiles of Neuroendocrine Gene Expression in the Preoptic Area of Male Rats

Endocrinology ◽  
2009 ◽  
Vol 150 (5) ◽  
pp. 2308-2316 ◽  
Author(s):  
Deena M. Walker ◽  
Thomas E. Juenger ◽  
Andrea C. Gore
Keyword(s):  
Molecular Mechanisms ◽  
Preoptic Area ◽  
Reproductive Function ◽  
Gonadal Hormones ◽  
Male Rats ◽  
Low Density ◽  
Sprague Dawley ◽  
Serum Hormones ◽  
Sprague Dawley Rats ◽  
Steroid Sensitive

Reproductive function is controlled by GnRH cells and their steroid-sensitive regulatory inputs. The proper maturation of this system is critical to sexual development and maintenance of adult function. However, the molecular mechanisms underlying these developmental changes, and the potential roles of gonadal hormones in sculpting these processes, have not been fully explored. We performed a developmental profile from postnatal day (P) 1 through P60 of a network of five genes in the preoptic area (POA) that are critical to reproduction in male Sprague Dawley rats. GnRH, estrogen receptors-α, and -β, androgen receptor (AR), and progesterone receptor (PR) mRNAs in the POA were assayed, and serum hormones were measured, in developing male rats. We also used a Taqman low-density array to identify candidate genes that may be important in development. Of the five targeted genes, only AR and PR changed robustly (7- and 3- to 4-fold increases, respectively) during development. All of the gonadal serum hormones changed markedly and with very different patterns from their receptor mRNAs: testosterone decreased from P1 to P30 and then increased to P60; progesterone peaked on P30; and estradiol decreased from P1 to P30. Using the Taqman low-density array, we identified several genes that changed dramatically in the POA with development, particularly G protein-coupled receptor 30, IGF-I, vitamin D receptor, estrogen-related receptor-α, and thyroid receptor-α. Our data demonstrate developmental stage-specific changes in neuroendocrine genes, particularly AR and PR. Moreover, the relationships between hormones and their corresponding receptors undergo dynamic changes across development in male rats.

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