scholarly journals Spontaneous Primary Pleural Mesothelioma in Fischer 344 (F344) and Other Rat Strains: A Retrospective Review

2021 ◽  
pp. 019262332110536
Author(s):  
Debra A. Tokarz ◽  
Margarita M. Gruebbel ◽  
Gabrielle A. Willson ◽  
Jerry F. Hardisty ◽  
Gail Pearse ◽  
...  
Keyword(s):  
Retrospective Review ◽  
Female Rats ◽  
Male Rats ◽  
Sprague Dawley ◽  
Rat Strains ◽  
Incidence Data ◽  
Fischer 344 ◽  
Male And Female Rats ◽  
Microscopic Evaluation ◽  
F344 Rats

Spontaneous primary pleural mesotheliomas in Fischer 344 (F344) or other rat strains have rarely been reported. The objectives of this retrospective study were to develop historical incidence data and better characterize the light-microscopic morphology of these naturally occurring neoplasms in a large cohort of rats of several strains. A retrospective review was performed of National Toxicology Program (NTP) studies in rats conducted between 1980 and 2019 and comprising a total of 104,029 rats (51,326 males, 52,703 females), predominantly (90%) of the F344 strain. Of the 94,062 F344 rats surveyed, there were 30 cases of primary pleural mesotheliomas (22 males, 8 females). Of the 2998 Wistar Han rats surveyed, primary pleural mesotheliomas were present in 2 male rats. No primary pleural mesotheliomas were noted in male and female rats of other strains (6669 Sprague Dawley; 300 Osborne-Mendel). All primary pleural mesotheliomas in control and treated F344 and Wistar Han rats were considered spontaneous and unrelated to treatment. Based on light-microscopic evaluation of paraffin-embedded hematoxylin and eosin stained sections, only epithelioid and biphasic histologic subtypes were observed: 18 and 12 in F344 rats, respectively, and one each in Wistar Han rats. No sarcomatoid subtype cases were noted in any strain of rat.

Comparison of the acute hematotoxicity of 2-butoxyethanol in male and female F344 rats

2000 ◽  
Vol 19 (3) ◽  
pp. 185-192 ◽  
Author(s):  
B I Ghanayem ◽  
S M Ward ◽  
B Chanas ◽  
A Nyska
Keyword(s):  
Body Weight ◽  
Cell Volume ◽  
Weight Ratio ◽  
Female Rats ◽  
Male Rats ◽  
Mean Cell Volume ◽  
Male And Female ◽  
Male And Female Rats ◽  
Butoxyacetic Acid ◽  
F344 Rats

Administration of 2-butoxyethanol (BE) to rodents causes acute hemolytic anemia, and metabolic activation of BE to butoxyacetic acid (BAA) is required for the development of this effect. Recent studies have shown that female rats treated with BE exhibit a variety of histopathologic lesions that are absent in males and many of these lesions are attributed to the hemolytic effects of BE. Current studies were designed to compare the acute hematotoxicity of BE in male and female F344 rats. Rats were treated with 250 mg BE/kg body weight or water (control; 5 ml/kg) by gavage. At 4, 8, or 24 h after dosing, rats were anesthetized, blood was collected by cardiac puncture, and various blood parameters were measured. BE resulted in a time-dependent swelling of erythrocytes as evidenced by an early increase in hematocrit (Hct) and mean cell volume (MCV) in male rats. In contrast, increased Hct in female rats did not accompany an increase in MCV. It is likely that hemolysis was so severe at 4 h that Hct exhibited a decline in female rats at that time point. Subsequently, red blood cell (RBCs), hemoglobin concentration (Hgb), and Hct declined as hemolysis progressed. However, the onset of BE-induced hemolysis was faster in female compared to male rats. These effects were also associated with a significant increase in the spleen weight to body weight ratio. Blood smears were also prepared and morphological changes evaluated by light microscopy included stomatocytosis, spherocytosis, and schistocytosis. Furthermore, aggregation of RBCs in female rats as evidenced by increased formation of rouleaux was observed at 24 h after BE administration. These effects were observed earlier and more frequently in female rats. No differences in the sensitivity of RBCs obtained from male and female rats and exposed to butoxyacetic acid (BAA) in vitro was observed as determined by measuring the packed cell volume. In conclusion, these data suggest that female rats are more sensitive to hemolysis and morphological alterations of erythrocytes induced by BE during the first 24 h after exposure compared to males. It is likely that the greater sensitivity of female rats to BE effects on RBCs may account for the reported development of thrombosis and tissue infarction in female rats.

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

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.

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

Hypertension ◽  
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.

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

1992 ◽  
Vol 29 (2) ◽  
pp. 145-151 ◽  
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.

Effects of sex and exercise training on β-adrenoreceptor mediated opposition of evoked sympathetic vasoconstriction in resting and contracting muscle of rats

2020 ◽  
Author(s):  
Ian R. Cooper ◽  
Sixue Liu ◽  
Darren S. DeLorey
Keyword(s):  
Exercise Training ◽  
Triceps Surae ◽  
Female Rats ◽  
Male Rats ◽  
Sprague Dawley ◽  
Contracting Muscle ◽  
Arterial Blood ◽  
Male And Female Rats ◽  
Sympathetic Vasoconstriction ◽  
Main Effect

This study investigated the hypothesis that β-adrenoreceptor mediated inhibition of sympathetic vasoconstriction would be enhanced in female compared to male rats, and that exercise training would augment β-adrenoreceptor inhibition of sympathetic vasoconstriction in male and female rats. Sprague-Dawley rats were randomized into sedentary (Male: n=7; Female: n=8) and exercise trained (Male: n=9; Female: n=9) groups. Following 4 weeks of exercise training or sedentary behavior, rats were anesthetized and surgically instrumented for stimulation of the lumbar sympathetic chain, muscle contraction and measurement of arterial blood pressure and femoral artery blood flow (FBF). Femoral vascular conductance (FVC) was calculated as FBF/mean arterial pressure. The percentage change of FVC in response to sympathetic stimulation delivered at 2 and 5 Hz was measured at rest and during contraction of the triceps surae muscles before and after β-adrenoreceptor blockade (Propranolol;0.075 mg·kg-1, IV). We found that, at rest, β-adrenoreceptor blockade decreased (main effect of drug, 2Hz: P <0.001; 5Hz: P<0.001) sympathetic vasoconstriction. During contraction, sympathetic vasoconstrictor responsiveness was lower (main effect of sex, 2Hz: P=0.001; 5Hz: P=0.023) in female compared to male rats, and sympatholysis was enhanced (main effect of sex, 2 Hz: P=0.001; 5Hz: P<0.001) in female rats. β-adrenoreceptor blockade decreased (main effect of drug, 2Hz: P=0.049; 5Hz: P<0.001) evoked sympathetic vasoconstriction in contracting muscle. The present study demonstrated that β-adrenoreceptors do not blunt sympathetic vasoconstriction in resting or contracting skeletal muscle of male or female rats. Sympatholysis was enhanced in female rats, however, this was not attributable to β-adrenoreceptor mediated blunting of sympathetic vasoconstriction.

Aging and fluid homeostasis in rats

1997 ◽  
Vol 273 (4) ◽  
pp. R1441-R1450 ◽  
Author(s):  
Neil E. Rowland ◽  
Annie Morien ◽  
Mircea Garcea ◽  
Melvin J. Fregly
Keyword(s):  
Female Rats ◽  
Male Rats ◽  
Acute Administration ◽  
Salt Appetite ◽  
Sprague Dawley ◽  
Cross Sectional ◽  
Aging Rats ◽  
Fluid Homeostasis ◽  
Male And Female Rats ◽  
Age Related

The capacity of aging rats to defend body fluid homeostasis in response to a variety of dipsogenic and natriorexigenic stimuli was assessed. Male and female rats of both the Fischer 344 (FR) and Sprague-Dawley (SD) strains were used and tested at target ages of ∼5, 10, 15, and 20 mo in both longitudinal and cross-sectional studies. There were no consistent age-related declines in water intake in response to water deprivation or acute administration of hypertonic NaCl; angiotensin (ANG) I, II, III; or isoproterenol. Likewise, there were no major impairments in either urinary excretion of the hypertonic NaCl load or excretion of water or hypotonic NaCl loads, although the latter were excreted more slowly in the older cohorts. The preference/aversion functions for NaCl solutions differed between SD and FR rats, but did not change with age except in male FR rats that lost their aversion to dilute NaCl at 20 mo of age. Intake of hypotonic NaCl solution after acute sodium depletion (furosemide treatment) showed a partial decline with age, and the older rats sustained larger estimated sodium deficits after a 6-h repletion period. A more complete age-related decline was observed in the intake of hypertonic NaCl stimulated by chronic dietary administration of a kininase II inhibitor (ramipril). Male rats of 15–20 mo of age showed no ramipril-induced sodium appetite. Brain ANG II receptor density, determined by autoradiography, declined by almost 50% in the paraventricular nucleus at 20 mo of age and declined slightly in the organum vasculosum laminae terminalis but did not decline in either the supraoptic nucleus or subfornical organ. Thus the major deficits in fluid intake in aging rats are related to salt appetite; the mechanism was not identified definitively.

scholarly journals A vapor exposure method for delivering heroin alters nociception, body temperature and spontaneous activity in female and male rats

2020 ◽  
Author(s):  
Arnold Gutierrez ◽  
Kevin M. Creehan ◽  
Michael A. Taffe
Keyword(s):  
Body Temperature ◽  
Spontaneous Activity ◽  
Female Rats ◽  
Male Rats ◽  
Sprague Dawley ◽  
Exposure System ◽  
Male And Female ◽  
Male And Female Rats ◽  
Sprague Dawley Rats

AbstractBackgroundThe ongoing crisis related to non-medical use of opioids makes it of continued importance to understand the risk factors for opioid addiction, the behavioral and neurobiological consequences of opioid exposure and to seek potential avenues for therapy. Pre-clinical rodent models have been critical to advancing understanding of opioid consequences for decades, but have been mostly limited to drug delivery by injection or by oral dosing. Inhalation, a significant route for many human users, has not been as well-established.MethodWe adapted an e-cigarette based exposure system, previously shown efficacious for delivery of other drugs to rats, to deliver heroin vapor. Effects in vivo were assessed in male and female Sprague-Dawley rats using a warm-water assay for anti-nociception and an implanted radiotelemetry system for evaluating changes in body temperature and spontaneous activity rate.ResultsInhalation of vapor created by heroin 100 mg/mL in the propylene glycol (PG) vehicle significantly slowed tail-withdrawal from a 52°C water bath, bi-phasically altered activity, and increased temperature in male and female rats. Inhalation of heroin 50 mg/mL for 15 minutes produced significant effects, as the lower bound on efficacy, whereas inhalation of heroin 100 mg/mL for 30 minutes produced robust effects across all endpoints and groups.ConclusionsThis work shows that e-cigarette devices deliver psychoactive doses of heroin to rats, using concentrations of ∼50-100 mg/mL and inhalation durations of 15-30 minutes. This technique may be useful to assess the health consequences of inhaled heroin and other opioid drugs.

scholarly journals Alcohol and Vapourized Nicotine Co-Exposure During Adolescence Contribute Differentially to Sex-Specific Behavioural Effects in Adulthood

2021 ◽  
Author(s):  
Jessica Ruffolo ◽  
Jude Frie ◽  
Hayley Thorpe ◽  
Malik Talhat ◽  
Jibran Khokhar
Keyword(s):  
Alcohol Drinking ◽  
Preference Test ◽  
Alcohol Preference ◽  
Female Rats ◽  
Fear Learning ◽  
Male Rats ◽  
Sprague Dawley ◽  
Adult Rats ◽  
Male And Female ◽  
Male And Female Rats

Introduction: Co-occurrence of e-cigarette use and alcohol consumption during adolescence is frequent. However, little is known about their long-lasting effects when combined. Here, we examined whether adolescent co-exposure to alcohol drinking and vapourized nicotine would impact reward- and cognition-related behaviours in adult male and female rats during adulthood. Methods: Four groups of male and female Sprague Dawley rats (n=8-11/group/sex) received either nicotine (JUUL 5% nicotine pods) or vehicle vapour daily between postnatal days 30-46, while having continuous voluntary access to ethanol and water during this time in a two-bottle preference design. Upon reaching adulthood, rats underwent behavioural testing utilizing Pavlovian conditioned approach testing, fear conditioning and a two-bottle alcohol preference test. Results: A sex-dependent effect was found in the two-bottle preference test in adulthood such that females had a higher intake and preference for alcohol compared to males regardless of adolescent exposure; both male and female adult rats had greater alcohol preference compared to adolescents. Male rats exposed to vapourized nicotine with or without alcohol drinking during adolescence exhibited altered reward-related learning in adulthood, evidenced by enhanced levels of sign-tracking behaviour. Male rats that drank alcohol with or without nicotine vapour in adolescence showed deficits in associative fear learning and memory as adults. In contrast, these effects were not seen in female rats exposed to alcohol and nicotine vapour during adolescence. Conclusions: The present study provides evidence that co-exposure to alcohol and vapourized nicotine during adolescence in male, but not female, rats produces long-term changes in reward- and cognition-related behaviours.

Oral Toxicity Evaluation of Thiodiglycol in Sprague-Dawley Rats

2014 ◽  
Vol 33 (5) ◽  
pp. 393-402 ◽  
Author(s):  
Richard A. Angerhofer ◽  
Mark W. Michie ◽  
Glenn J. Leach ◽  
Mark S. Johnson ◽  
Gunda Reddy
Keyword(s):  
Body Weight ◽  
Food Consumption ◽  
Sulfur Mustard ◽  
Female Rats ◽  
Male Rats ◽  
Control Individual ◽  
Sprague Dawley ◽  
Oral Toxicity ◽  
Male And Female Rats ◽  
Sprague Dawley Rats

Thiodiglycol (TDG) is the main product of sulfur mustard hydrolysis and is an environmental contaminant. Subacute and subchronic oral toxicity studies with TDG were conducted in Sprague-Dawley rats. Neat TDG was administered by gavage at doses of 157, 313, 625, 1250, 2500, 5000, and 9999 mg/kg/d, 5 days per week, for 14 days. In the 14-day study, decreased body weight and food consumption were observed at 5000 mg/kg/d. In the 90-day study, rats received neat TDG at doses of 50, 500, or 5000 mg/kg/d for 5 days per week. A fourth group served as a sham control. Individual body weight and food consumption were measured weekly. At termination of the experiment, urine, blood, and tissue samples were collected. Rats displayed significant decreased body weight with no effect on food consumption following administration of TDG at 5000 mg/kg/d. Both male and female rats showed significant increased kidney weights at 5000 mg/kg/d. The organ to body weight ratios increased significantly for liver, kidneys, testes, and brain in males and adrenals in females for 5000 mg/kg/d. At all doses of TDG, hematological and clinical parameters and tissue histopathology remained unaltered. The no observed adverse effect level (NOAEL) for oral subchronic toxicity was 500 mg/kg/d. Benchmark dose (BMD) was derived from the decreased gain in body weight that was seen in male rats. A BMD based on a 10% decrease in body weight was 1704 mg/kg/d, and the lower confidence limit on the dose BMD, the BMDL, was 372 mg/kg/d.

The growth and antigenicity of the metacestodes of Taenia crassiceps in several different strains of rats

1981 ◽  
Vol 55 (3) ◽  
pp. 209-222 ◽  
Author(s):  
J. Chernin
Keyword(s):  
Female Rats ◽  
Male Rats ◽  
Sprague Dawley ◽  
Taenia Crassiceps ◽  
Male And Female Rats ◽  
Sprague Dawley Rats ◽  
Significant Difference ◽  
Antigenic Expression ◽  
Outbred Strain ◽  
Different Strains

ABSTRACTThe metacestodes of Taenia crassiceps removed from a stock infection of Sprague Dawley rats were injected into seven inbred and one outbred strain of rats. The results showed that over-all female rats are more susceptible to the infection than male rats. Only one strain of rat, the Lewis male rats, was found to be resistant to the infection. There was no significant difference in the volume of metacestodes recovered from the male and female rats. The sizes of the metacestodes, after two passages through the rats, were compared to those of the original mouse strain and it was found that metacestodes from two strains of rats were significantly smaller. The antigenic expression of the metacestodes from the different strains of rats was compared and some variation in the antigenicity was observed.

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