Effects of leptin on sperm count and morphology in Sprague-Dawley rats and their reversibility following a 6-week recovery period

Andrologia ◽  
2014 ◽  
Vol 47 (7) ◽  
pp. 751-758 ◽  
Author(s):  
F.A. Almabhouh ◽  
K. Osman ◽  
I. Siti Fatimah ◽  
G. Sergey ◽  
J. Gnanou ◽  
...  
Keyword(s):  
Sperm Count ◽  
Recovery Period ◽  
Sprague Dawley ◽  
Sprague Dawley Rats ◽  
Sperm Count And Morphology

Evaluation of Reproductive Development Following Intravenous and Oral Exposure to DEHP in Male Neonatal Rats

2003 ◽  
Vol 22 (3) ◽  
pp. 159-174 ◽  
Author(s):  
Jon N. Cammack ◽  
Randy D. White ◽  
Donovan Gordon ◽  
Jerome Gass ◽  
Lawrence Hecker ◽  
...  
Keyword(s):  
Sperm Count ◽  
Liver Weight ◽  
Oral Exposure ◽  
Seminiferous Tubules ◽  
Primary Group ◽  
Sprague Dawley ◽  
Intravenous Injections ◽  
Sprague Dawley Rats ◽  
Recovery Group ◽  
Ethylhexyl Phthalate

Di-(2-ethylhexyl)phthalate (DEHP) was administered to 3- to 5-day-old male Sprague-Dawley rats by daily intravenous injections of 60, 300, or 600 mg/kg/day or by daily oral gavage of 300 or 600 mg/kg/day for 21 days. Histopathological evaluation and organ weight measurements were performed on some animals after 21 days of dosing (primary group) and later on the recovery group animals that were held without further treatment until sexual maturity at approximately 90 days of age. No effects of any type were observed in animals treated intravenously with 60 mg/kg/day. Testicular changes, consisting of a partial depletion of the germinal epithelium and/or decrease in diameter of seminiferous tubules, were present in all animals of the 300- and 600-mg/kg/day groups after the 21-day dosing period. Testes weight decreased and liver weight increased in these animals. Testes changes were dose-related and generally more severe among animals dosed orally versus intravenously. In the recovery animals, a residual DEHP-induced decrease in seminiferous tubule diameter was present in the testis of several animals dosed orally at 300 and 600 mg/kg/day, but not in animals dosed intravenously. There was no germinal cell depletion or Sertoli cell alteration observed in any dose group at any time. Notably, no effects on sperm count, sperm morphology, or sperm motility were observed at 90 days of age in any of the groups.

scholarly journals Transcriptomic Impact of IMA-08401, a Novel AHR Agonist Resembling Laquinimod, on Rat Liver

2019 ◽  
Vol 20 (6) ◽  
pp. 1370 ◽  
Author(s):  
Stephenie Prokopec ◽  
Raimo Pohjanvirta ◽  
Selma Mahiout ◽  
Lars Pettersson ◽  
Paul Boutros
Keyword(s):  
Recovery Period ◽  
Oxidative Stress Response ◽  
Sprague Dawley ◽  
Aryl Hydrocarbon ◽  
Sprague Dawley Rats ◽  
Low Toxicity ◽  
Repeated Dosing ◽  
Transcriptomic Changes ◽  
Subacute Exposure

IMA-08401 (C2) is a novel aryl hydrocarbon receptor (AHR) agonist and selective AHR modulator (SAHRM) that is structurally similar to laquinimod (LAQ). Both compounds are converted to the AHR-active metabolite DELAQ (IMA-06201) in vivo. SAHRMs have been proposed as therapeutic options for various autoimmune disorders. Clinical trials on LAQ have not reported any significant toxic outcomes and C2 has shown low toxicity in rats; however, their functional resemblance to the highly toxic AHR agonist 2,3,7,8-tetrachlorodibenzo-p-dioxin (TCDD) raises questions. Here, we characterize the hepatic transcriptomic changes induced by acute (single-dose) and subacute exposure (repeated dosing for 5 days followed by a 5-day recovery period) to C2 in Sprague-Dawley rats. Exposure to C2 leads to activation of the AHR, as shown by altered transcription of Cyp1a1. We identify a heightened response early after exposure that drops off by day 10. Acute exposure to C2 leads to changes to transcription of genes involved in antiviral and antibacterial responses, which highlights the immunomodulator effects of this AHR agonist. Subacute exposure causes an oxidative stress response in the liver, the consequences of which require further study on target tissues such as the CNS and immune system, both of which may be compromised in this patient population.

scholarly journals A 90-day Sub-chronic Oral Toxicity Assessment of Mulberry Extract in Sprague Dawley Rats

2021 ◽  
Vol 58 ◽  
pp. 004695802110560
Author(s):  
Min Hong ◽  
Min Lu ◽  
Yimin Qian ◽  
Liping Wei ◽  
Yaqun Zhang ◽  
...  
Keyword(s):  
Clinical Chemistry ◽  
Recovery Period ◽  
Safety Evaluation ◽  
Toxicity Assessment ◽  
Sprague Dawley ◽  
Oral Toxicity ◽  
Renal Tubular Cells ◽  
Sprague Dawley Rats ◽  
Adverse Effect Level ◽  
Renal Tubular

Mulberry extract from Fructus Mori contains an anthocyanin pigment and has been widely used as a food additive in China and other Eastern Asian countries. Only few research has been done on toxicological profiling of mulberry extract for its safety evaluation; however, the data is inconclusive. In the current study, mulberry extract of 4200, 1400, or 466 mg/kg were orally administrated to Sprague Dawley rats for 90 consecutive days followed by a recovery period of 28 days. No abnormalities were detected in body weights, food intake, ophthalmological, hematological, coagulation, clinical chemistry, and organ weights parameters. Discoloration of urine (red, purple, and brown) and feces (black), along with bedding material (purple) were observed in the 4200 mg/kg group. Further, microscopic examination revealed brown granules in the renal tubular cells for rats in 4200 and 1400 mg/kg groups. Since these changes were associated with excretory effect of the extract, the No Observed Adverse Effect Level was determined to be 4200 mg/kg, which was equivalent to the 1058.5 mg/kg of anthocyanin.

Corticosterone-responsive and -unresponsive metabolic characteristics of adrenalectomized rats

1994 ◽  
Vol 267 (3) ◽  
pp. R799-R804 ◽  
Author(s):  
C. R. Hamelink ◽  
P. J. Currie ◽  
J. W. Chambers ◽  
T. W. Castonguay ◽  
D. V. Coscina
Keyword(s):  
Metabolic Pathways ◽  
Recovery Period ◽  
Fat Metabolism ◽  
Light Period ◽  
Preoperative Period ◽  
Sprague Dawley ◽  
Metabolic Characteristics ◽  
Sprague Dawley Rats ◽  
Postsurgical Recovery ◽  
Adrenalectomized Rats

Glucocorticoids are important in influencing substrate flux through the metabolic pathways. This study was designed to answer the question "Does adrenalectomy (ADX) cause a shift toward fat metabolism as measured by a decrease in respiratory quotient (RQ)?" Male Sprague-Dawley rats were divided into four groups, ADX, ADX + 20% corticosterone (Cort) (ADX-20%), ADX + 40% Cort (ADX-40%), or sham-operated controls (Sham). ADX-20% received 50 mg and ADX-40% 100 mg Cort dissolved in 250-mg cholesterol pellets and placed subcutaneously. Each rat was monitored for 90 min four times both during a preoperative period and again after a 1-wk postsurgical recovery period in an indirect calorimeter. Cort prevented ADX-induced suppression of weight gain and food intake. ADX decreased motoric activity in both the light and dark periods. Cort restored activity to Sham levels. ADX decreased RQ only in the dark (0.858 ADX vs. 0.891 Sham) and was reversed only in the ADX-40% group. Energy expenditure (EE) was depressed in both the light and dark by ADX; Cort partially restored EE to Sham values in the light period.

scholarly journals Simulated Aeromedical Evacuation in a Polytrauma Rat Model

2019 ◽  
Vol 90 (12) ◽  
pp. 1016-1025
Author(s):  
Françoise Arnaud ◽  
Georgina Pappas ◽  
Eric Maudlin-Jeronimo ◽  
Carl Goforth
Keyword(s):  
Rat Model ◽  
Recovery Period ◽  
White Blood Cells ◽  
Mass Casualties ◽  
Sprague Dawley ◽  
Aeromedical Evacuation ◽  
Risk Of Mortality ◽  
Sprague Dawley Rats ◽  
Combat Casualties ◽  
Volume Controlled

BACKGROUND: Hemorrhage and traumatic brain injury can be lethal if left unattended. The transportation of severely wounded combat casualties from the battlefield to higher level of care via aeromedical evacuation (AE) may result in unintended complications. This could become a serious concern at the time of evacuation of mass casualties or for prolonged field care scenarios with limited resources.METHODS: Following instrumentation (t1), anesthetized Sprague-Dawley rats were injured or not [75-kPa blast and 30% estimated blood-volume controlled hemorrhage] (t2). After 15 min, all rats were resuscitated with saline. During the simulated 3-h evacuation, 8000 ft (2440 m) vs. sea-level heart rate, temperature, and oxygenation (Spo2) were continuously recorded. One group of rats was euthanized immediately after evacuation (t3) and another after a 72-h recovery period (t4). Hematology and metabolic levels were measured at t1, t2, t3, and t4.RESULTS: Survival was 100% in control-uninjured animals, 83% in injured animals under normobaria, and significantly reduced to 50% under hypobaria. This AE setting resulted in significantly lower hemodynamics, thermoregulation, and oxygenation parameters in the animals under hypobaria than those under normobaria. The initial lower mean arterial pressure (MAP) with the reduced oxygen level before AE were critical factors for the survival of injured animals. We observed a general increase of white blood cells and platelet ability to aggregate at t4 in all experimental groups.CONCLUSION: Physiological parameters were affected during aeromedical evacuation in all groups. This was worsened for injured animals with MAP less than 60 mmHg associated with low Spo2 in a simulated aeromedical evacuation. This represented a high risk of mortality for severely polytraumatized animals.Arnaud F, Pappas G, Maudlin-Jeronimo E, Goforth C. Simulated aeromedical evacuation in a polytrauma rat model. Aerosp Med Hum Perform. 2019; 90(12):1016–1025.

scholarly journals Juvenile toxicity study of Gossence™ (galactooligosaccharides) in Sprague Dawley rats

2020 ◽  
Vol 4 ◽  
pp. 239784732091321
Author(s):  
Manish Jain ◽  
Moninder Kaur ◽  
Deepika Pandey Tiwari ◽  
Chandrashekara Vishwanath ◽  
Nataraju Javaregowda ◽  
...  
Keyword(s):  
Clinical Chemistry ◽  
Pediatric Population ◽  
Recovery Period ◽  
Clinical Signs ◽  
Weighted Average ◽  
Organ Weight ◽  
High Dose ◽  
Average Dose ◽  
Sprague Dawley ◽  
Sprague Dawley Rats

Gossence™ (galactooligosaccharide; GOS) is a prebiotics and used as one of the major constituents in infant milk formulas that act as a functional food. Gossence is manufactured by Tata Chemicals Ltd, India, through a patented process of biotransformation of lactose. A toxicology study in juvenile rats was carried out to assess the safety profile of Gossence intended for pediatric population. The objective of this study is to assess the potential systemic toxicity of Gossence when administered through gavage at dose levels of 1000, 2000, or 5000/3000 mg/kg/day (equivalent to 1347, 2694, and 6735/4041 mg/kg/day of GOS, respectively) to juvenile Sprague Dawley rats from postnatal day (PND) 4 to PND 52 (i.e. total 49 days of dosing period). A separate group of animals were treated with vehicle (purified Milli Q water) for a similar duration. The following parameters were evaluated during the study period: morbidity/mortality check, clinical signs, body weights, body weight changes, food consumption, functional observational battery, motor activity, postnatal developmental observations, hematology, clinical chemistry, urinalysis, organ weight, gross pathology, and histopathology. During dosing phase, the high-dose group, 5000 mg/kg/day, was reduced to 3000 mg/kg/day (equivalent to 4041 mg/kg/day dose of GOS) from day 16 (PND 19) onward, due to clinical signs of watery feces and yellow color stains at urogenital region and mortality in two animals on day 15 (PND 18) of the study. Time-weighted average dose for 5000 mg/kg/day was equivalent to 3600 mg/kg/day. No further deaths or clinical signs were noticed in animals at 3000 mg/kg/day from day 18 (PND 21) of dosing phase to until terminal euthanization. At the terminal euthanization, there were no test item-related gross changes observed in all surviving rats except for, an increased cecum size in some of the rats at 5000/3000 mg/kg/day, which correlated with the increased weights of cecum with contents during organ weight recording, but this had no correlating light microscopic changes during histological examination. The cecal enlargement was completely recovered following the 14-day recovery period. The no-observedadverse-effect level is 3000 mg/kg/day for Gossence, which is equivalent to 4041 mg/kg/day of GOS in both sexes.

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.

Hypothyroidism increases serotonin turnover and sympathetic activity in the adult rat

1991 ◽  
Vol 69 (2) ◽  
pp. 205-210 ◽  
Author(s):  
W. N. Henley ◽  
X. Chen ◽  
C. Klettner ◽  
L. L. Bellush ◽  
M. A. Notestine
Keyword(s):  
Recovery Period ◽  
Normalization Procedure ◽  
Sprague Dawley ◽  
Creatinine Excretion ◽  
Adult Rat ◽  
Sympathetic Function ◽  
Sham Surgery ◽  
Sprague Dawley Rats ◽  
Serotonin Turnover ◽  
Colonic Temperature

Adult, male Sprague–Dawley rats underwent surgical thyroidectomy (Tx) or sham surgery. In all three experiments from which data are reported, a 3-week recovery period was allowed. In experiments I and II, baseline measurements of colonic temperature (Tc) and urinary norepinephrine excretion (NE) were obtained, and both variables were monitored daily for the duration of the studies. After baseline measurements, half of each surgical group was given either triiodothyronine (T3) or vehicle injections subcutaneously; in experiment I replacements continued for 1.5 days, while in experiment II T3 replacement continued for 3.5 days. Rats were decapitated at the end of each experiment and serotonin (5-HT) turnover was measured in brainstem. Serotonin turnover in rostral and caudal brainstem was increased with Tx (p < 0.05). Increased turnover in caudal brainstem was normalized by T3 only in experiment II. Similarly, decreased Tc and elevated NE with Tx were normalized in experiment II but not in experiment I. In experiment III, NE measurements normalized on a creatinine excretion basis indicated that increased NE is evident with Tx, irrespective of normalization procedure. Significant correlations between 5-HT in caudal brainstem and metabolic correlates of sympathetic function, concurrent normalization of NE and 5-HT in caudal brainstem, plus work from other laboratories describing sympathoexcitatory serotonergic neurons located in me caudal brainstem suggest that the central and peripheral changes in me hypothyroid rat are causally related.Key words: triiodothyronine, norepinephrine, serotonin, brainstem, metabolism.

scholarly journals Evaluation of the AV7909 Anthrax Vaccine Toxicity in Sprague Dawley Rats Following Three Intramuscular Administrations

2021 ◽  
pp. 109158182110312
Author(s):  
Veena V. Rao ◽  
C. Steven Godin ◽  
Michael J. Lacy ◽  
Jon R. Inglefield ◽  
Sukjoon Park ◽  
...  
Keyword(s):  
Protective Antigen ◽  
Recovery Period ◽  
Clinical Pathology ◽  
Systemic Toxicity ◽  
Thigh Muscle ◽  
Post Exposure Prophylaxis ◽  
Sprague Dawley ◽  
Regional Lymph Nodes ◽  
Anthrax Vaccine ◽  
Sprague Dawley Rats

AV7909 is a next-generation anthrax vaccine under development for post-exposure prophylaxis following suspected or confirmed Bacillus anthracis exposure, when administered in conjunction with the recommended antibacterial regimen. AV7909 consists of the FDA-approved BioThrax® vaccine (anthrax vaccine adsorbed) and an immunostimulatory Toll-like receptor 9 agonist oligodeoxynucleotide adjuvant, CPG 7909 . The purpose of this study was to evaluate the potential systemic and local toxicity of AV7909 when administered via repeat intramuscular injection to the right thigh muscle (biceps femoris) to male and female Sprague Dawley rats. The vaccine was administered on Days 1, 15, and 29 and the animals were assessed for treatment-related effects followed by a 2-week recovery period to evaluate the persistence or reversibility of any toxic effects. The AV7909 vaccine produced no apparent systemic toxicity based on evaluation of clinical observations, body weights, body temperature, clinical pathology, and anatomic pathology. Necrosis and inflammation were observed at the injection sites as well as in regional lymph nodes and adjacent tissues and were consistent with immune stimulation. Antibodies against B. anthracis protective antigen (PA) were detected in rats treated with the AV7909 vaccine, confirming relevance of this animal model for the assessment of systemic toxicity of AV7909. In contrast, sera of rats that received saline or soluble CPG 7909 alone were negative for anti-PA antibodies. Overall, 3 intramuscular immunizations of Sprague Dawley rats with AV7909 were well tolerated, did not induce mortality or any systemic adverse effects, and did not result in any delayed toxicity.

scholarly journals Impact of Moriamin Forte on Testicular and Epididymal Damage in Rats with Oligoasthenospermia

2021 ◽  
Vol 2021 ◽  
pp. 1-9
Author(s):  
Xing Zhou ◽  
Guo-Wei Zhang ◽  
Wei-Ning Liang ◽  
Yi-Ze Li ◽  
Song Xu ◽  
...  
Keyword(s):  
Group Treatment ◽  
Sperm Count ◽  
Testicular Tissue ◽  
Control Group ◽  
High Dose ◽  
Sprague Dawley ◽  
Sprague Dawley Rats ◽  
Antioxidase Activity ◽  
Motility Of Sperm ◽  
Related Proteins

To investigate the effect and mechanism of action of Moriamin Forte (MF) on oligoasthenospermia (OA) in rats exposed to multiglycosides of Tripterygium wilfordii (GTW), forty male Sprague Dawley rats were randomly divided into four groups. Rats in the control group were treated with 0.5% sodium carboxymethyl cellulose. The remaining rats were administered GTW (30 mg/kg/d) for 40 d to establish an OA model. Concurrently, the groups were treated with normal saline and low-dose (100 mg/kg/d) and high-dose (200 mg/kg/d) MF, respectively. After treatment, the number and motility of sperm cells were examined. Testicular and epididymal histomorphology changes were observed. Antioxidant indicators (SOD, CAT, MDA, TAC, and Nrf2) in testicular and epididymal tissues were detected. Apoptotic and antiapoptotic indicators (Bax and Bcl2 expression) in the testicular tissue were measured by immunohistochemistry. GTW decreased sperm count and motility, damaged testicular and epididymis tissues, impaired antioxidase activity, and increased tissue MDA levels. Meanwhile, GTW upregulated the expression of Bax and downregulated the expression of Bcl2. Western blot analysis demonstrated a decrease in the Nrf2 expression in the model group. Treatment with MF improved sperm count and motility, as well as inhibited the rate of apoptosis in the rat reproductive system. Moreover, MF improved the activity of antioxidants and increased the relative expression of the antioxidant pathway-related protein Nrf2. In conclusion, MF may reverse the GTW-induced OA by modulating the expression of apoptotic and antioxidant pathway-related proteins. This study may provide a pharmacological foundation for the use of MF in OA treatment.

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