Impact of 30-Day Oral Dosing with N-acetyl-l-cysteine on Sprague-Dawley Rat Physiology

2004 ◽  
Vol 23 (4) ◽  
pp. 239-247 ◽  
Author(s):  
Darryl P. Arfsten ◽  
Eric W. Johnson ◽  
Angie R. Thitoff ◽  
Anne E. Jung ◽  
Erin R. Wilfong ◽  
...  
Keyword(s):  
Chemical Exposure ◽  
Average Weight ◽  
Activity Levels ◽  
Sprague Dawley ◽  
Oral Dosing ◽  
Sd Rats ◽  
Negative Controls ◽  
The Impact ◽  
Gst Activity

A number of studies have demonstrated a protective effect associated with N-acetyl-l-cysteine (NAC) against toxic chemical exposure. However, the impact of long-term oral dosing on tissue pathology has not been determined. In this study, the authors assessed the impact of long-term oral NAC administration on organ histopathology and tissue glutathione (GSH) and total glutathione- S-transferase (GST) activity levels in Sprague-Dawley (SD) rats. Groups of 20 SD rats (10 males, 10 females), 8 weeks of age, were dosed daily by oral gavage with deionized H2O (negative controls) or NAC solution at a rate of 600 or 1200 mg/kg/day for 30 days. Animals were euthanized 6 h after treatment on study day 30. There were no significant differences in final body weights or weekly average weight gain between treatment groups. Serum alanine amino-transferase (ALT) activities were significantly elevated ( p ≤.05) in NAC-treated animals compared to controls when measured on study day 30. Histopathologic evaluation of the stomach, small intestine, liver, kidneys, spleen, thymus, and lungs revealed no lesions associated with NAC administration. When measured on study day 30, total GST activity for kidney and skin from NAC-treated animals were increased 39% to 131% as compared to controls. Tissue GSH concentrations from NAC-treated animals were increased 24% to 81% as compared with negative controls. Further studies are needed to determine if the observed increase in tissue GSH concentration and GST activity provide a degree of chemoprotection against dermal and systemic chemical toxicants.

scholarly journals The long-term bio-behavioural effects of juvenile sildenafil treatment in Sprague-Dawley versus Flinders Sensitive Line rats

2021 ◽  
pp. 1-20
Author(s):  
Juandré Lambertus Bernardus Saayman ◽  
Stephanus Frederik Steyn ◽  
Christiaan Beyers Brink
Keyword(s):  
Sprague Dawley ◽  
Long Term Effects ◽  
Bdnf Level ◽  
Treatment Groups ◽  
Sd Rats ◽  
Behavioural Effects ◽  
Sensitive Line ◽  
Level Analysis ◽  
Flinders Sensitive Line

Abstract Objective: To investigate the long-term effects of juvenile sub-chronic sildenafil (SIL) treatment on the depressive-like behaviour and hippocampal brain-derived neurotrophic factor (BDNF) levels of adult Sprague-Dawley (SD) versus Flinders Sensitive Line (FSL) rats. Methods: SD and FSL rats were divided into pre-pubertal and pubertal groups, whereafter 14-day saline or SIL treatment was initiated. Pre-pubertal and pubertal rats were treated from postnatal day 21 (PND21) and PND35, respectively. The open field and forced swim tests (FST) were performed on PND60, followed by hippocampal BDNF level analysis one day later. Results: FSL rats displayed greater immobility in the FST compared to SD rats (p < 0.0001), which was reduced by SIL (p < 0.0001), regardless of treatment period. Hippocampal BDNF levels were unaltered by SIL in all treatment groups (p > 0.05). Conclusion: Juvenile sub-chronic SIL treatment reduces the risk of depressive-like behaviour manifesting during young adulthood in genetically susceptible rats.

Growth, metabolism, and blood pressure disturbances during aging in transgenic rats with altered brain renin-angiotensin systems

2005 ◽  
Vol 23 (3) ◽  
pp. 311-317 ◽  
Author(s):  
Sherry O. Kasper ◽  
Christy S. Carter ◽  
Carlos M. Ferrario ◽  
Detlev Ganten ◽  
Leon F. Ferder ◽  
...  
Keyword(s):  
Blood Pressure ◽  
Systolic Pressure ◽  
Normal Brain ◽  
Sprague Dawley ◽  
Transgenic Rats ◽  
Serum Leptin ◽  
Renin Angiotensin ◽  
Insulin Levels ◽  
Sd Rats

Transgenic rats with targeted decreased glial expression of angiotensinogen (ASrAogen rats) did not show an increase in systolic pressure compared with Sprague-Dawley (SD) rats during aging (15–69 wk of age). ASrAogen animals had lower body weights throughout the study, similar to reports for animals with systemic knockout of angiotensinogen or treated long term with renin-angiotensin system (RAS) blockers. Further characterization of indexes of growth and metabolism in ASrAogen rats compared with (mRen2)27 and SD rats, which express elevated versus normal brain and tissue angiotensin II levels, respectively, revealed that serum leptin was 100–200% higher in SD and (mRen2)27 rats at 46 wk and 69 wk of age. Consistent with low serum leptin, ASrAogen rats had higher food intake (73%) compared with SD or (mRen2)27 rats. (mRen2)27 rats had higher resting insulin levels than ASrAogen rats at all ages. Insulin levels were constant during aging in ASrAogen rats, whereas an increase occurred in SD rats, leading to higher insulin levels at 46 and 69 wk of age compared with ASrAogen rats. IGF-1 was comparable among strains at all ages, but (mRen2)27 rats had longer and ASrAogen rats had shorter tail lengths versus SD rats at 15 wk of age. In conclusion, reduced expression of glial angiotensinogen blunts the age-dependent rise in insulin levels and weight gain, findings that mimic the effects of long-term systemic blockade of the RAS or systemic knockout of angiotensinogen. These data implicate glial angiotensinogen in the regulation of body metabolism as well as hormonal mechanisms regulating blood pressure.

Synaptic plasticity in sympathetic ganglia from acquired and inherited forms of ouabain-dependent hypertension

2001 ◽  
Vol 281 (2) ◽  
pp. R635-R644 ◽  
Author(s):  
Azeez A. Aileru ◽  
Aline De Albuquerque ◽  
John M. Hamlyn ◽  
Paolo Manunta ◽  
Jui R. Shah ◽  
...  
Keyword(s):  
Blood Pressure ◽  
Sympathetic Neurons ◽  
Long Term Potentiation ◽  
Sympathetic Ganglia ◽  
Sprague Dawley ◽  
Sd Rats ◽  
Term Potentiation ◽  
Compound Action Potentials ◽  
Cervical Ganglia

Altered sympathetic nervous system activity has been implicated often in hypertension. We examined short-term potentiation [posttetanic potentiation (PTP)] and long-term potentiation (LTP) in the isolated superior cervical ganglia (SCG) from Sprague-Dawley (SD) rats given vehicle, digoxin, or ouabain by subcutaneous implants as well as in animals with ouabain-induced hypertension (OHR), and inbred Baltimore ouabain-resistant (BOR) and Baltimore ouabain-sensitive (BOS) strains of rats. Postganglionic compound action potentials (CAP) were used to determine PTP and LTP following a tetanic stimulus (20 Hz, 20 s). Baseline CAP magnitude was greater in ganglia from OHR than in vehicle-treated SD rats before tetanus, but the decay time constant of PTP was significantly decreased in OHR and in rats infused with digoxin that were normotensive. In hypertensive BOS and OHR, the time constants for the decay of both PTP and LTP ( t L) were increased and correlated with blood pressure (slope = 0.15 min/mmHg, r = 0.52, P < 0.047 and 6.7 min/mmHg, r = 0.906, P < 0.0001, respectively). In BOS and OHR, t L (minutes) was 492 ± 40 ( n = 7) and 539 ± 41 ( n = 5), respectively, and differed ( P < 0.05) from BOR (257 ± 48, n = 4), SD vehicle rats (240 ± 18, n = 4), and captopril-treated OHR (370 ± 52, n = 5). After the tetanus, the CAP at 90 min in BOS and OHR SCG declined less rapidly vs. SD vehicle rats or BOR. Captopril normalized blood pressure and t L in OHR. We conclude that the duration of ganglionic LTP and blood pressure are tightly linked in ouabain-dependent hypertension. Our results favor the possibility that enhanced duration of LTP in sympathetic neurons contributes to the increase in sympathetic nerve activity in ouabain-dependent hypertension and suggest that a captopril-sensitive step mediates the link of ouabain with LTP.

Effects of prenatal ethanol exposure on choline-induced long-term depression in the hippocampus

2021 ◽  
Author(s):  
Erin L Grafe ◽  
Christine J Fontaine ◽  
Jennifer D Thomas ◽  
Brian R Christie
Keyword(s):  
Choline Chloride ◽  
Hippocampal Slices ◽  
Ethanol Exposure ◽  
Acute Administration ◽  
Prenatal Ethanol Exposure ◽  
Sprague Dawley ◽  
Long Term Depression ◽  
M1 Receptors ◽  
The Impact

Choline is an essential nutrient that is being explored as a nutritional treatment for many neurological disorders. Indeed, choline has already moved to being used in clinical trials for Fetal Alcohol Spectrum Disorders (FASD), and there is increased pressure to better understand its therapeutic mechanism(s) of action. This is particularly true given its potential to directly effect synaptic mechanisms that are believed important for cognitive processes. In the current work we study how the direct application of choline can affect synaptic transmission in hippocampal slices obtained from adolescent (post-natal days 21-28) Sprague-Dawley rats (Rattus norvegicus). The acute administration of choline chloride (2 mM) reliably induced a long-term depression (LTD) of field excitatory postsynaptic potentials (fEPSP) in the DG in vitro. The depression required the involvement of M1-receptors, and the magnitude of the effect was similar in slices obtained from male and female animals. To further study the impact of choline in an animal model of FASD, we examined offspring from dams fed an ethanol-containing diet (35.5% ethanol-derived calories) throughout gestation. In slices from the adolescent animals that experienced prenatal ethanol exposure (PNEE), we found that the choline induced an LTD that uniquely involved the activation of NMDA and M1 receptors. This study provides a novel insight into how choline can modulate hippocampal transmission at the level of the synapse and that it can have unique effects following PNEE.

Mortality of Sprague Dawley (SD) Rat on Long Term High-Fat Diet (HFD)

2021 ◽  
Vol 4 (1) ◽  
Author(s):  
Christianus Rustin ◽  
Zulhabri Othman ◽  
Muhammad Fakhruddin Irfan Bin Sazali
Keyword(s):  
Sudden Death ◽  
Chronic Inflammation ◽  
High Fat Diet ◽  
Cardiac Tissue ◽  
Future Research ◽  
Sprague Dawley ◽  
High Fat ◽  
Sd Rat ◽  
Sd Rats

Background and Objective: Heart failure is linked with metabolic syndrome due to an unbalanced dietary intake. Previous studies suggest that cardiac dysfunction is related to chronic inflammation due to injury within the heart muscle. This study focused on the examination and sudden death of Sprague Dawley (SD) rat which was on long-term High-Fat Diet (HFD). The outcomes will potentially provide an insight into future research in sudden death due to HFD. Methods: Total of 15 SD rats grouped into ten HFD and five on normal diet (ND); Female SD rats on HFD underwent physical examination, tissue analysis 12 hours post-death using Hematoxylin & Eosin (H&E) followed by morphological assessment and SD rats from ND used as control. Microscopic images processed using ImageJ and data analysis performed in SPSS software. Results: No significant physical trauma prior to death, however on the 60th day SD rat suffered chronic inflammation to cardiac tissues with Lee Index (LI) of 0.30, indicated the occurrence of Myocardial infarction (MI). The average mean between the size area of inflammation and the region on cardiac tissue is (834.19 ± 103.41) and 94.2% of inflammation activities explained by the four random regions of cardiac tissue (R2= 0.942, F(1, 2)= 32.401, p< 0.05), with every one unit increase in the size area of inflammation, the infected region of cardiac tissue is estimated to increase at 0.970 (?= 0.970, p< 0.05). Conclusion: Chronic inflammation resulted in myocardial injuries led to mortality of SD rats largely due to HFD.

Abstract 296: Norepinephrine Evoked Salt-Sensitive Hypertension Results in Impaired NCC Function, but Not Expression

Hypertension ◽  
2013 ◽  
Vol 62 (suppl_1) ◽  
Author(s):  
Kathryn Walsh ◽  
Sarah Mahne ◽  
Jill T Kuwabara ◽  
Richard D Wainford
Keyword(s):  
Salt Intake ◽  
Pcr Analysis ◽  
Kidney Cortex ◽  
Sprague Dawley ◽  
Sodium Homeostasis ◽  
Sd Rats ◽  
High Salt Intake ◽  
Induced Hypertension ◽  
Salt Sensitive Hypertension ◽  
The Impact

Aim: Recent controversial studies have proposed that excess norepinephrine (NE) evokes impaired NCC regulation to drive salt-sensitive hypertension. The following studies examine the impact of excess NE on salt-sensitivity and sodium homeostasis in conscious Sprague-Dawley (SD) rats. Methods: Naïve male SD rats, rats receiving a s.c. vehicle infusion (DMSO/Saline, 50:50), or rats receiving a s.c. NE infusion (600ng/min) were fed a 0.4% (NS) or 8% NaCl (HS) diet for 14 days. Additional rats received s.c. hydrochlorothiazide (HCTZ, 4mg/kg/d) in combination with NE (600ng/min) for 14 days on HS. On day 14, MAP, FENa, MAP response to i.v. hexamethonium (30mg/kg), and peak natriuresis to i.v. HCTZ (2mg/kg) infusion were assessed (N=4/gp). A PCR array examining NCC associated genes was performed on kidney cortex samples from each group. Results: NE increased MAP, FENa and vascular sympathetic tone (MAP [mmHg] NS 127±2, NE+NS 151±3, p<0.05). We observed no difference between the naïve and vehicle rats. A HS diet exacerbated NE induced hypertension (MAP [mmHg] HS 129±2, NE+HS 172±4, p<0.05), reduced FENa and prevented a salt stimulated reduction in HCTZ evoked natriuresis. Co-infusion of HCTZ with NE abolished the salt-sensitive component of NE-induced hypertension (MAP [mmHg] NE+HCTZ+HS: 152±3, p<0.05). PCR analysis revealed a significant increase in serine/threonine kinase 39 (0.83-fold increase vs. Naïve SD on NS) mRNA in NE+HS rats. We did not see NE or HS evoked changes in OSR-1, WNK4 or NCC mRNA in any group. Conclusion: The results support previous studies in mice and highlight an opposing interaction between excess NE and high salt intake on sodium homeostasis which exacerbated NE-induced hypertension via a mechanism independent of NE-mediated vascular constriction. Physiologically, our results show impaired NCC function, supporting previous data. In contrast, we failed to detect elevated NCC or WNK4 mRNA in response to NE infusion contradicting data generated in mice and suggesting a key role of altered NCC phosphorylation versus expression in NE treated rats.

Expression of hypoglossal long-term facilitation differs between substrains of Sprague-Dawley rat

2001 ◽  
Vol 4 (3) ◽  
pp. 175-181 ◽  
Author(s):  
D. D. FULLER ◽  
T. L. BAKER ◽  
M. BEHAN ◽  
G. S. MITCHELL
Keyword(s):  
Neural Plasticity ◽  
Genetic Influences ◽  
Hypoglossal Nucleus ◽  
Sprague Dawley ◽  
Sd Rat ◽  
Sd Rats ◽  
Episodic Hypoxia ◽  
Serotonin Immunoreactivity ◽  
Long Term Facilitation

Long-term facilitation (LTF) is a prolonged, serotonin-dependent augmentation of respiratory motor output following episodic hypoxia. Previous observations lead us to hypothesize that LTF is subject to genetic influences and, as a result, differs between Sprague-Dawley (SD) rats from two vendors, Harlan (H) and Charles River Laboratories/Sasco (CRL/S). Using a blinded experimental design, we recorded integrated phrenic (∫Phr) and hypoglossal neurograms in anesthetized, vagotomized, paralyzed, and ventilated rats. At 60 min following three 5-min hypoxic episodes (PaO2 = 40 ± 1 Torr; 5-min hyperoxic intervals), ∫Phr was elevated from baseline in both SD substrains (i.e., LTF; P < 0.05). Conversely, hypoglossal LTF was present in CRL/S but not H rats ( P < 0.05 between substrains). Serotonin immunoreactivity within the hypoglossal nucleus was not different between H and CRL/S rats. We conclude that the expression of hypoglossal LTF differs between SD rat substrains, indicating a difference in their genetic predisposition to neural plasticity.

scholarly journals Comparative Incidences and Biological Outcomes for Thymoma in Various Rat Strains in National Toxicology Program Studies

2019 ◽  
Vol 47 (7) ◽  
pp. 833-841
Author(s):  
Rebecca R. Moore ◽  
Hiroaki Nagai ◽  
Rodney A. Miller ◽  
Jerry F. Hardisty ◽  
Neil Allison ◽  
...  
Keyword(s):  
Cause Of Death ◽  
Early Mortality ◽  
Sprague Dawley ◽  
Rat Strains ◽  
Fischer 344 ◽  
National Toxicology Program ◽  
Sd Rats ◽  
Biological Outcomes ◽  
Long Term Studies

Thymomas from 277 Fischer 344/N (F344/N), 10 Sprague Dawley (HSD:Sprague Dawley SD) (SD), 129 Wistar Han [Crl:WI(Han)] (WH), and 4 Wistar Outbred (WO) rats were reviewed from long-term studies in the National Toxicology Program (NTP) database. The incidence of thymomas in F344/N rats was slightly higher in males than in females, while the incidences in SD and WH rats were higher in females than in males. Only male WO rats were used in NTP studies. Of the 277 thymomas in F344/N rats, 235 (84.8%) were benign and 42 (15.2%) malignant, 14 of which exhibited metastasis. Of the 10 thymomas in SD rats, 5 (50%) were benign and 5 (50%) were malignant, one of which exhibited metastasis. Of the 129 thymomas in WH rats, 126 (98%) were benign and 3 (2%) were malignant, 1 with metastasis. Of the 4 thymomas in WO rats, 3 (75%) were benign and 1 (25%) was malignant, with no metastases. Malignant thymomas in F344/N and WH rats showed a propensity to be the cause of death and to result in early mortality, whereas the benign thymomas were associated less often with decreased survival. No occurrences of this neoplasm were reported to be related to exposure to any test articles.

scholarly journals Solar rotational cycle in lightning activity in Japan during the 18–19th centuries

2018 ◽  
Vol 36 (2) ◽  
pp. 633-640 ◽  
Author(s):  
Hiroko Miyahara ◽  
Ryuho Kataoka ◽  
Takehiko Mikami ◽  
Masumi Zaiki ◽  
Junpei Hirano ◽  
...  
Keyword(s):  
Solar Activity ◽  
Solar Rotation ◽  
Galactic Cosmic Rays ◽  
Activity Level ◽  
Lightning Activity ◽  
Activity Levels ◽  
Rotational Period ◽  
Solar Activity Level ◽  
The Impact

Abstract. Thunderstorm and cloud activities sometimes show a 27-day period, and this has long been studied to uncover a possible important link to solar rotation. Because the 27-day variations in the solar forcing parameters such as solar ultraviolet and galactic cosmic rays become more prominent when the solar activity is high, it is expected that the signal of the 27-day period in meteorological phenomena may wax and wane according to the changes in the solar activity level. In this study, we examine in detail the intensity variations in the signal of the 27-day solar rotational period in thunder and lightning activity from the 18th to the 19th centuries based on 150-year-long records found in old diaries kept in Japan and discuss their relation with the solar activity levels. Such long records enable us to examine the signals of solar rotation at both high and low solar activity levels. We found that the signal of the solar rotational period in the thunder and lightning activity increases as the solar activity increases. In this study, we also discuss the possibility of the impact of the long-term climatological conditions on the signals of the 27-day period in thunder/lightning activities. Keywords. Meteorology and atmospheric dynamics (lightning)

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