Blockade of beta adrenergic receptors protects the blood brain barrier and reduces systemic pathology caused by HIV-1 Nef protein

Combination antiretroviral therapy (cART) targets viral replication, but early viral protein production by astrocytes may still occur and contribute to the progression of HIV-1 associated neurocognitive disorders and secondary complications seen in patients receiving cART. In prior work with our model, astrocytic HIV-1 Nef expression exhibits neurotoxic effects leading to neurological damage, learning impairment, and immune upregulation that induces inflammation in the lungs and small intestine (SI). In this follow-up study, we focus on the sympathetic nervous system (SNS) as the important branch for peripheral inflammation resulting from astrocytic Nef expression. Male and female Sprague Dawley rats were infused with transfected astrocytes to produce Nef. The rats were divided in four groups: Nef, Nef + propranolol, propranolol and naïve. The beta-adrenergic blocker, propranolol, was administered for 3 consecutive days, starting one day prior to surgery. Two days after the surgery, the rats were sacrificed, and then blood, brain, small intestine (SI), and lung tissues were collected. Levels of IL-1β were higher in both male and female rats, and treatment with propranolol restored IL-1β to basal levels. We observed that Nef expression decreased staining of the tight junction protein claudin-5 in brain tissue while animals co-treated with propranolol restored claudin-5 expression. Lungs and SI of rats in the Nef group showed histological signs of damage including larger Peyer’s Patches, increased tissue thickness, and infiltration of immune cells; these findings were abrogated by propranolol co-treatment. Results suggest that interruption of the beta adrenergic signaling reduces the peripheral organ inflammation caused after Nef expression in astrocytes of the brain.

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Absorption, Distribution, Excretion, and Pharmacokinetics ofC-Pyronaridine Tetraphosphate in Male and Female Sprague-Dawley Rats

Journal of Biomedicine and Biotechnology ◽

10.1155/2010/590707 ◽

2010 ◽

Vol 2010 ◽

pp. 1-9 ◽

Cited By ~ 2

Author(s):

Sang Hyun Park ◽

Kannampalli Pradeep

Keyword(s):

Clinical Trials ◽

Small Intestine ◽

Oral Administration ◽

Female Rats ◽

Sprague Dawley ◽

Male And Female ◽

Phase Ii Clinical Trials ◽

Male And Female Rats ◽

Sprague Dawley Rats ◽

Peak Value

The main objective of this investigation was to determine the absorption, distribution, excretion, and pharmacokinetics of the antimalarial drug pyronaridine tetraphosphate (PNDP) in Sprague-Dawley rats. Following oral administration of a single dose (10 mg/Kg) ofC-PNDP, it was observed that the drug was readily absorbed from the small intestine within 1 hour following oral administration and was widely distributed in most of the tissues investigated as determined from the observed radioactivity in the tissues. The peak value of the drug in the blood was reached at around 8 hours postadministration, and radioactivity was detected in most of the tissues from 4 hours onwards.C-PNDP showed a poor permeability across the blood-brain barrier, and the absorption, distribution, and excretion ofC-PNDP were found to be gender-independent as both male and female rats showed a similar pattern of radioactivity. Excretion of the drug was predominantly through the urine with a peak excretion post 24 hours of administration. A small amount of the drug was also excreted in the feces and also in the breath. It was found that theCmax, AUC (0-inf), andTmaxvalues were similar to those observed in the Phase II clinical trials of pyronaridine/artesunate (Pyramax) conducted in Uganda.

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Toxicity Evaluation of a Traditional Polyherbal Unani Formulation Jawarish Shahi in Rats

The Journal of Phytopharmacology ◽

10.31254/phyto.2018.7502 ◽

2018 ◽

Vol 7 (5) ◽

pp. 412-418

Author(s):

Mohd Urooj ◽

◽

Mohammad Ahmed Khan ◽

G. Thejaswini ◽

Munawwar Husain Kazmi ◽

...

Keyword(s):

Body Weight ◽

Feed Intake ◽

Clinical Signs ◽

Female Rats ◽

Control Group ◽

Sprague Dawley ◽

Male And Female ◽

Salix Caprea ◽

Male And Female Rats ◽

Dose Levels

Jawarish Shahi (JS) is a compound polyherbal Unani pharmacopoeial formulation indicated for Khafqan (Palpitation), Nafkh-e-Shikam (Flatulence) and Waswas (Insanity; false perception and hallucinations). Jawarish Shahi contains herbs like Halela (Terminalia chebula), Amla (Emblica officinalis), Kishneez (Coriandrum sativum), Elaichi Khurd, (Elettaria cardamomum), and Bed Mushk (Salix caprea). The present study was carried out as per OECD 408 guidance to evaluate 90 days repeated oral dose toxicity in male and female Sprague Dawley rats. The study was performed at dose levels 1028 and 2000 mg/kg bw. No adverse effects were reported with respect to body weight, feed intake, behavior and clinical signs indicative of systemic toxicity. The expected growth pattern was observed in body weight and feed intake as compared to control group at both dose levels in male and female rats. There were few significant alterations with respect to hematology, and clinical biochemistry, however the results were within normal range thus considered toxicologically insignificant. The microscopic examination of different organ/tissue showed that no histopathological changes were observed. The findings of the study showed that No Observed Adverse Effect Level (NOAEL) for JS is greater than 2000 mg/kg body weight

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Biosynthesis of corticosterone and deoxycorticosterone in sprague-dawley male and female rats after administration of 7,12-dimethylbenzanthracene

Journal of Steroid Biochemistry ◽

10.1016/0022-4731(77)90195-9 ◽

1977 ◽

Vol 8 (9) ◽

pp. 971-976 ◽

Cited By ~ 2

Author(s):

Serge Carreau ◽

Françoise Joubert ◽

André Chemama ◽

Michel Drosdowsky

Keyword(s):

Female Rats ◽

Sprague Dawley ◽

Male And Female ◽

Male And Female Rats

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Intraperitoneal Alfaxalone and Alfaxalone–Dexmedetomidine Anesthesia in Sprague–Dawley Rats (Rattus norvegicus)

Journal of the American Association for Laboratory Animal Science ◽

10.30802/aalas-jaalas-19-000161 ◽

2020 ◽

Vol 59 (5) ◽

pp. 531-538

Author(s):

Sylvia E West ◽

Jonathan C Lee ◽

Tinika N Johns ◽

Elizabeth A Nunamaker

Keyword(s):

Rattus Norvegicus ◽

Female Rats ◽

Male Rats ◽

Sprague Dawley ◽

Male And Female ◽

Withdrawal Reflex ◽

Male And Female Rats ◽

Sprague Dawley Rats ◽

Laboratory Rodent ◽

Physiologic Parameters

Due to their unpredictability and variable effects, injectable anesthetic regimens in laboratory rodent species warrant refinement. In our study we sought to evaluate alfaxalone, which has gained recent popularity in veterinary medicine, alone and in combination with dexmedetomidine to evaluate their anesthetic ability in Sprague–Dawley rats when administered intraperitoneally. Three doses of alfaxalone only and 4 dose combinations of alfaxalone-dexmedetomidine were tested in males and female rats. The time to induction, anesthetic duration, pulse rate, respiratory rate, temperature, and time to recovery were recorded by a blind observer. The level of anesthesia induced by the various anesthetic protocols was assessed by using pedal withdrawal reflex to a noxious stimulus and scored according to the response. Dependent on the treatment group, atipamezole or saline was administered intraperitoneally once animals reached 60 min of anesthesia. Regardless of the dose, alfaxalone alone achieved only a sedative level of anesthesia, whereas all alfaxalone-dexmedetomidine combinations led to a surgical level of anesthesia in all animals. Anesthesia regimens using alfaxalone alone and in combination with dexmedetomidine demonstrated sex-associated differences, with female rats maintaining longer durations of sedation or anesthesia than their male counterparts. Both male and female rats displayed decreases in physiologic parameters consistent with the effects of dexmedetomidine. Given the results described herein, we recommend 20 mg/kg alfaxalone for sedation and 30 mg/kg alfaxalone combined with 0.05 mg/kg dexmedetomidine for surgical anesthesia in female rats. Appropriate doses of alfaxalone only and alfaxalone-dexmedetomidine for male rats were not determined in this study and need further evaluation.

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Administration of ursolic acid to new-born pups prevents dietary fructose-induced non-alcoholic fatty liver disease in Sprague Dawley rats

Journal of Developmental Origins of Health and Disease ◽

10.1017/s2040174420000124 ◽

2020 ◽

pp. 1-12

Author(s):

Nyasha C. Mukonowenzou ◽

Rachael Dangarembizi ◽

Eliton Chivandi ◽

Pilani Nkomozepi ◽

Kennedy H. Erlwanger

Keyword(s):

Fluid Intake ◽

Female Rats ◽

Surrogate Markers ◽

Sprague Dawley ◽

Alcoholic Fatty Liver ◽

Male And Female ◽

Hepatic Lipid Accumulation ◽

Male And Female Rats ◽

Dietary Fructose ◽

Alcoholic Fatty Liver Disease

Abstract Overconsumption of fructose time dependently induces the development of non-alcoholic fatty liver disease (NAFLD). We investigated whether ursolic acid (UA) intake by new-born rats would protect against fructose-induced NAFLD. One hundred and seven male and female Sprague Dawley rat pups were randomly grouped and gavaged (10 ml/kg body weight) with either 0.5% dimethylsulphoxide (vehicle control), 0.05% UA, 50% fructose mixed with UA (0.05%) or 50% fructose alone, from postnatal day 6 (P6) to P20. Post-weaning (P21–P69), the rats received normal rat chow (NRC) and water to drink. On P70, the rats in each group were continued on water or 20% fructose to drink, as a secondary high fructose diet during adulthood. After 8 weeks, body mass, food and fluid intake, circulating metabolites, visceral adiposity, surrogate markers of liver function and indices of NAFLD were determined. Food intake was reduced as a result of fructose feeding in both male and female rats (p < 0.0001). Fructose consumption in adulthood significantly increased fluid intake and visceral adiposity in female rats (p < 0.05) and had no apparent effects in male rats (p > 0.05). In both sexes of rats, fructose had no significant (p > 0.05) effects on body mass, circulating metabolites, total calorie intake and surrogate markers of hepatic function. Fructose consumption in both early life and adulthood in female rats promoted hepatic lipid accumulation (p < 0.001), hypertrophy, microvesicular and macrovesicular steatosis (p < 0.05). Early-life UA intake significantly (p < 0.001) reduced fructose-induced hepatic lipid accumulation in both male and female rats. Administration of UA during periods of developmental plasticity shows prophylactic potential against dietary fructose-induced NAFLD.

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Abstract 386: Compound 21 Induces Natriuresis via Renal AT2 Receptor Activation in Male and Female Rats

Hypertension ◽

10.1161/hyp.60.suppl_1.a386 ◽

2012 ◽

Vol 60 (suppl_1) ◽

Author(s):

Brandon A Kemp ◽

Nancy L Howell ◽

Robert M Carey

Keyword(s):

Receptor Activation ◽

Female Rats ◽

Male Rats ◽

Sprague Dawley ◽

Male And Female ◽

Male And Female Rats ◽

Sprague Dawley Rats ◽

Angiotensin Iii ◽

Compound 21 ◽

Renal Cortical Interstitium

Endogenous renal des-aspartyl 1 -angiotensin II (angiotensin III) activates renal proximal tubule AT 2 receptors (AT 2 Rs) and induces natriuresis via a nitric oxide-cyclic GMP signaling pathway. The present study explores the ability of highly selective non-peptide AT 2 R agonist Compound 21 (C21) to induce natriuresis. Sprague-Dawley rats (12 weeks old; male N=22; female N=18) were studied in the presence and absence of concurrent 24-h AT 1 R blockade with candesartan (CAND;0.01 mg/kg/min). Rats were anesthetized with Inactin 100 mg/kg i.p., uninephrectomized and instrumented for delivery of 3 cumulative 30-min i.v. infusions of C21 (100, 200, and 300 ng/kg/min) following a 30-min control infusion of vehicle. Mean arterial pressure (MAP) was measured for all periods and urine Na + excretion rate (U Na V) was calculated for the control and final C21 collection periods. To determine whether the systemically induced natriuresis is mediated by renal AT 2 Rs, PD-123319 (PD), a specific AT 2 R antagonist, was infused directly into the renal cortical interstitium(20 μg/kg/min and 10 μg/kg/min for females and males, respectively) during the i.v. C21 infusions. In female rats, C21 increased U Na V from 1.5 ± 0.20 to 7.48 ± 0.95 μmol/min (P<0.0001). This response was abrogated by concurrent intrarenal PD infusion [control 0.74 ± 0.19 vs. C21 2.02 ± 0.50 μmol/min (P<0.001from C21 alone). Systemic CAND administration augmented the natriuretic response to C21 [control 1.29 ± 0.25 vs. C21 10.68 ± 0.70 μmol/min (P<0.05 from C21 alone)]. In male rats, C21 increased U Na V from 0.46 ±0.08 to 6.21 ± 1.33 μmol/min (P<0.01). This response was blocked by concurrent intrarenal PD infusion [control 0.39 ± 0.11 vs. C21 1.69 ± 0.53 μmol/min (P<0.05 from C21 alone). Systemic CAND did not significantly alter the natriuretic response to C21 alone [control 0.49 ± 0.15 vs. C21 7.67 ± 0.72 μmol/min (P = NS from C21 alone). In female rats, CAND augmented the natriuretic response to C21 over that of male rats (P<0.01). Systemic arterial pressures were decreased by CAND in both male and female rats but were unchanged by C21 alone or together with intrarenal PD. C21 induces natriuresis via renal AT 2 R activation in both male and female rats. These data suggest the potential for AT 2 R agonist therapy in hypertension.

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Effect of Strain and Sex on the Induction of Hyperalbuminaemic Proteinuria in the Rat

Clinical Science ◽

10.1042/cs0610751 ◽

1981 ◽

Vol 61 (6) ◽

pp. 751-756 ◽

Cited By ~ 15

Author(s):

Gillian M. Lawrence ◽

D. B. Brewer

Keyword(s):

Relevant Literature ◽

Inbred Strains ◽

Female Rats ◽

Sprague Dawley ◽

Male And Female ◽

Bovine Albumin ◽

Male And Female Rats ◽

Ultrastructural Damage ◽

Parenteral Protein

1. Male and female rats representing the four inbred strains [Wistar (albino), Sprague-Dawley (albino), DA (brown) and PVG (hooded) rats] were injected intraperitoneally with 4.5-5.5 mg of Cohn V bovine albumin day−1 g−1 body wt. 2. the levels of proteinuria and glomerular ultrastructural damage induced in response to hyperalbuminaemia varied widely with the strain and sex of rat studied, being highest in the male Wistar and lowest in the male Sprague-Dawley. 3. A survey of the relevant literature shows that these results probably explain most of the reported inconsistencies and anomalies concerning the effect of parenteral protein injection in the rat.

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Influences of chemical sympathectomy and simulated weightlessness on male and female rats

Journal of Applied Physiology ◽

10.1152/jappl.1991.71.3.1005 ◽

1991 ◽

Vol 71 (3) ◽

pp. 1005-1014 ◽

Cited By ~ 12

Author(s):

C. R. Woodman ◽

C. S. Stump ◽

J. A. Stump ◽

L. A. Sebastian ◽

Z. Rahman ◽

...

Keyword(s):

Weight Bearing ◽

Mechanical Efficiency ◽

Female Rats ◽

Plasma Norepinephrine ◽

Chemical Sympathectomy ◽

Simulated Weightlessness ◽

Sprague Dawley ◽

Male And Female ◽

Male And Female Rats ◽

Sprague Dawley Rats

Maximum oxygen consumption (VO2max) has been shown to be reduced after periods of simulated weightlessness. To assess the role of the sympathetic nervous system in these reductions, Sprague-Dawley rats were either chemically sympathectomized (SYMX) or injected with saline (SHAM) and assigned to head-down suspension (HDS), horizontal restraint with the hindlimbs weight bearing (HWB), or cage-control (CC) conditions. VO2max, run time (RT), and mechanical efficiency (ME) were measured before suspension and on days 7 and 14. Male and female SHAM HDS groups exhibited reduced measures of VO2max (12–13%) after 7 and 14 days, and this decrease was attenuated in the SYMX and HWB rats. HDS resulted in a significant reduction in RT (9–15%) in both the male and female rats, and ME was significantly reduced after HDS in male and female SYMX and male SHAM rats (23–33%) but not in the female SHAM rats. Lesser reductions in ME were observed in the HWB rats. HDS and HWB were associated with lower body, fat-free, and fat masses, which were similar in male and female rats as well as for the SHAM and SYMX conditions. In a related HDS experiment with normal rats, plasma norepinephrine and epinephrine were increased by 53 and 42% after 7 days, but only epinephrine returned to baseline after 14 days. It was concluded that chemical sympathectomy and/or a weight-bearing stimulus will attenuate the loss in VO2max associated with simulated weightlessness in rats despite similar changes in body mass and composition. The mechanism(s) remains unclear at this time.

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Toxic Peripheral Neuropathy with Demyelination in Sprague-Dawley Rats Given CGS 21595 —A 5-Lipoxygenase Inhibitor

Veterinary Pathology ◽

10.1177/030098589202900207 ◽

1992 ◽

Vol 29 (2) ◽

pp. 145-151 ◽

Cited By ~ 2

Author(s):

D. E. Gunson ◽

P. S. Sahota ◽

W. O. Iverson ◽

R. Y. Chau ◽

G. M. McCormick ◽

...

Keyword(s):

Peripheral Neuropathy ◽

Recovery Period ◽

Female Rats ◽

Male Rats ◽

Renal Tubules ◽

Sprague Dawley ◽

Lipoxygenase Inhibitor ◽

Male And Female ◽

Male And Female Rats ◽

Sprague Dawley Rats

Male and female Sprague-Dawley rats were given CGS 21595, a pro-drug that is almost immediately metabolized to CGS 19213, a naphthoquinone that acts as a 5-lipoxygenase inhibitor. The compound was administered by gavage to five groups of Sprague-Dawley rats (group Nos. 1, 5, n = 30; group Nos. 2–4, n = 20) at daily doses of 0, 50, 150, 500, or 1,000 mg/kg for 13 weeks. Rats in the higher dose groups had a reduced weight gain, but significant neurologic signs were not observed. A peripheral neuropathy consisting predominantly of myelin destruction in the spinal nerve roots and sciatic nerves was seen in male rats treated with ≥ 150 mg/kg CGS 21595 and in female rats treated with ≥50 mg/kg CGS 21595 for 13 weeks. This lesion was not fully reversible after a recovery period of 4 weeks. Lesions consisted of ballooning of myelin sheaths, infiltration by macrophages, demyelination, and occasional areas of remyelination. Axons were generally preserved, and the brain and spinal cord were not affected. Male and female rats in all treatment groups had cytoplasmic hyaline droplets in the proximal renal tubules. This change was reversible after 4 weeks and was not associated with any other adverse effects on the kidney.

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