Dietary Administration of Colesevelam Hydrochloride Does Not Affect Fertility or Reproductive Performance in Rats

2004 ◽  
Vol 23 (6) ◽  
pp. 357-367 ◽  
Author(s):  
Judith K. Marquis ◽  
Rafif Dagher ◽  
Michael R. Jones
Keyword(s):  
Reproductive Performance ◽  
Sperm Count ◽  
Embryo Implantation ◽  
Sperm Concentration ◽  
Study Groups ◽  
Female Rats ◽  
Corpora Lutea ◽  
Sprague Dawley ◽  
Total Percentage ◽  
Male And Female Rats

Colesevelam hydrochloride (HCl) (WelChol; Sankyo Pharma) is a novel, highly potent, bile acid-binding polymer used for the treatment of hypercholesterolemia. The primary aim of this study was to determine the effects of dietarily administered colesevelam HCl on fertility and reproductive performance parameters. To assess these effects, sexually mature Sprague-Dawley rats were randomized to one of five treatment groups: feed alone, feed plus control article (SigmaCell), or feed plus colesevelam HCl 200, 1000, or 2000 mg/kg/day. Male and female rats were administered the appropriate group agent for 28 and 15 days, respectively, and were subsequently paired together for cohabitation and mating. Females continued to receive the test agent in their dietary formulation through presumed gestation day (GD) 7. Presumed pregnant females underwent cesarean section on GD 20. Food consumption rate, body weight, gross necropsy, and standard preclinical tests for reproduction and fertility were performed for each test animal. No statistically significant differences were found between control and drug-treated groups for any tested endpoints of reproduction. All animals placed in cohabitation successfully mated. Uterine and litter end points were unaffected by dosages of colesevelam HCl as high as 2000 mg/kg/day. There were no significant differences between treatment group litter averages in the number of corpora lutea, implantation sites, litter size, live fetuses, body weights, early/late resorptions, and the number of dams with viable fetuses. In addition, no external alterations of fetal morphology were attributable to treatment with colesevelam HCl when administered up to the embryo implantation stage. In male animals, no significant differences were found between the colesevelam HCl and control study groups in the average caudal epididymal sperm count or sperm concentration, total number of motile and nonmotile sperm, and the total percentage of motile sperm. Based on these data, colesevelam HCl does not have any significant adverse reproductive or fertility effects in rats, even when administered at doses approximately 30 times greater than the approved clinical dose.

scholarly journals Effects of Ethanolic Fruit Extract of Picralima nitida (Stapf) on Conception and Estrogenicity in Female Albino Rats

2017 ◽  
Vol 9 (4) ◽  
pp. 487-493
Author(s):  
Edmund MBEGBU ◽  
Chukwuka N. UCHENDU ◽  
Izuchukwu S. OCHIOGU
Keyword(s):  
Endometrial Thickness ◽  
Study Groups ◽  
Female Rats ◽  
Albino Rats ◽  
Corpora Lutea ◽  
Sprague Dawley ◽  
Fruit Extract ◽  
Immature Female ◽  
Crown Rump Length ◽  
Group 4

In search for medicinal plants with renowned reputation of contraceptive and fertility-modulating ability, this work was designed to evaluate the effects of ethanolic fruit extract of Picralima nitida on conception and oestrogenicity using twentyone sexually mature and twenty-four sexually immature female Sprague Dawley rats respectively. For the anti-conceptive study, 0 mg/kg, 50 mg/kg and 500 mg/kg of the extract was administered from day 1to day 4 of gestation (7 rats per group). On the 20th day of gestation, percentage of pregnant females (PPF), live foetal number (LFN), corpora lutea number (CLN), resorbed embryo number (REN), foetal crown-rump length (FCRL) and fertility indices (FI) were evaluated. For the anti-estrogenic study, Groups 1 to 3 (ovariectomized immature female rats) received 0.1 mg/kg of Stilboestrol, 50 mg/kg of the extract, and 0.2 ml of paraffin respectively, once daily for four consecutive days. Group 4 comprised of sham-operated immature female rats with their ovaries intact. The extract elicited absolute conception failure in 42.86% of the treated animals. The extract significantly (p < 0.05) reduced the FCRL, LFN and FI, but increased the REN. Evaluation of the allometric weights of the uterine tissues, endometrial thickness and vaginal opening revealed that the extract at 50 mg/kg body weight was antioestrogenic in activity. Findings from this research strongly suggest that the ethanolic fruit extract of Picralima nitida possesses significant post-coital anti-fertility activity in rats, which could not be attributed to its oestrogenic activity.

scholarly journals The Effect of Single and Triple Testicular Biopsy Using Biopty Gun on Spermatogenesis in Pubertal Rats

Animals ◽  
2021 ◽  
Vol 11 (6) ◽  
pp. 1569
Author(s):  
Tomislav Šušnjar ◽  
Ivana Kuzmić Prusac ◽  
Ivan Švagelj ◽  
Anđela Jurišić ◽  
Tomislav Šušnjar ◽  
...  
Keyword(s):  
Sperm Count ◽  
Semen Analysis ◽  
Study Groups ◽  
Testicular Biopsy ◽  
Male Rats ◽  
Lower Percentage ◽  
Control Group ◽  
Sprague Dawley ◽  
Left Testis ◽  
Significant Difference

Background: The aim of this study was to compare consequences in single and triple testicular biopsy by biopty gun in pubertal rats using histological and immunohistochemical analysis. Methods: Thirty-two Sprague-Dawley male rats were used as the experimental model. The rats were randomly divided into three study groups. The rats from the first group (n = 12) received a single-biopsy of upper pole of the left testis, while the rats from the second group (n = 10) received triple-biopsy of upper and lower poles and lateral surface of left testis. The third group (n = 10) was a control group. On the eightieth day after the biopsy in all rats bilateral orchiectomy and funiculectomy were performed to obtain testicular tissue and sperm for analysis. The consequences of the puncture were observed by pathohistology, immunohistochemistry and semen analysis. Results: The results of the study showed lower percentage of sperm count (14.5 mill/mL vs. 16 mill/mL, p = 0.130), sperm motility (24.6% vs. 32.7%, p > 0.05), abnormal sperm (30% vs. 27%, p > 0.05), atrophic tubules (21% vs. 6%, p < 0.001), volume (1.7 mL vs. 2.28 mL, p < 0.01) and apoptotic index (1.56 vs. 1.19, p = 0.650) in the testes with a triple-biopsy compared to the testes with a single-biopsy. Semen analysis showed a borderline significant difference between the group with triple-biopsy where sperm count was lower than it in the control group (14.5 mill/mL vs. 17.5 mill/mL, p = 0.05). A single-biopsy has little effect on the testis, especially on overall fertility. A triple-biopsy showed higher degree of the testicular damage but without a significant impact on overall fertility. Semen analysis showed that single- and triple-biopsies did not have a significant effect on sperm count, motility and morphology. Conclusion: Biopty gun procedure is a cheap, simple and reliable method for testicular biopsy in rats without a significant effect on sperm count, motility and morphology.

Prepubertal exposure to T-2 toxin advances pubertal onset and development in female rats via promoting the onset of hypothalamic–pituitary–gonadal axis function

2016 ◽  
Vol 35 (12) ◽  
pp. 1276-1285 ◽  
Author(s):  
R Yang ◽  
Y-M Wang ◽  
L Zhang ◽  
Z-M Zhao ◽  
J Zhao ◽  
...  
Keyword(s):  
Messenger Rna ◽  
Female Rats ◽  
Intragastric Administration ◽  
Corpora Lutea ◽  
Sprague Dawley ◽  
Trichothecene Mycotoxin ◽  
Pubertal Onset ◽  
Serum Hormone ◽  
Puberty Onset ◽  
High Level

T-2 toxin, a naturally produced Type A trichothecene mycotoxin, has been shown to damage the reproductive and developmental functions in livestocks. However, whether T-2 toxin can disturb the pubertal onset and development following prepubertal exposure remains unclear. To clarify this point, infantile female Sprague–Dawley rats were given a daily intragastric administration of vehicle or T-2 toxin at a dose of 375 μg/kg body weight for 5 consecutive days from postnatal day (PND) 15–19 (PND15–PND19). The days of vaginal opening, first diestrus, and first estrus in regular estrous cycle were advanced following T-2 toxin treatment, indicating prepubertal exposure to T-2 toxin induced the advancement of puberty onset. The relative weights of uterus and ovaries and the incidence of corpora lutea were all increased in T-2 toxin-treated rats; serum hormone levels of luteinizing hormone and estradiol and the messenger RNA expressions of gonadotropin-releasing hormone (GnRH) and GnRH receptor also displayed marked increases following exposure to T-2 toxin, all of which were well consistent with the manifestations of the advanced puberty onset. In conclusion, the present study reveals that prepubertal exposure to a high level of T-2 toxin promotes puberty onset in infantile female rats by advancing the initiation of hypothalamic–pituitary–gonadal axis function in female rats.

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

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

scholarly journals A Safety Evaluation of a Nature-Identical l-Ergothioneine in Sprague Dawley Rats

2016 ◽  
Vol 35 (5) ◽  
pp. 568-583 ◽  
Author(s):  
Palma Ann Marone ◽  
Jan Trampota ◽  
Steven Weisman
Keyword(s):  
Body Weight ◽  
Body Weight Gain ◽  
Antioxidant Properties ◽  
Metabolic Activation ◽  
Female Rats ◽  
Systemic Absorption ◽  
Test Substance ◽  
Sprague Dawley ◽  
Male And Female Rats ◽  
Sprague Dawley Rats

l-(+) Ergothioneine is a naturally occurring thiol amino acid with antioxidant properties and potential benefits as a dietary supplement. Despite its century-old identification and wide distribution in human food, little is known of its mechanism of action and safety. The nature-identical biomimetic of l-(+) ergothioneine, produced by Mironova Labs and supplied as Mironova (EGT+), has been investigated in the present studies for its mutagenic and toxicologic potential. In a plate incorporation and preincubation assay with Salmonella typhimurium strains TA98, 100, 1,535, and 1,537 and Escherichia coli WP2uvrA strain, at dose concentrations of 1.58, 5, 15.8, 50, 158, 500, 1,580, and 5,000 μg/plate with and without metabolic activation, no cytotoxicity or mutagenicity was observed. Following a preliminary 28-day study, a repeated dose 90-day gavage study at dose levels of 0, 400, 800, and 1,600 mg/kg body weight (bw)/d in Sprague Dawley rats, in which dose-proportional systemic absorption was confirmed by plasma analysis, no adverse clinical, body weight/gain, food consumption and efficiency, clinical pathology, or histopathological changes associated with the administration of the nature-identical ergothioneine were observed. In conclusion, EGT+ administered over 90 days was well tolerated with a no adverse effect level at 1,600 mg/kg bw/d, the highest dose tested for male and female rats. In addition, the nature-identical test substance, EGT+ was not mutagenic in a bacterial reverse mutation assay at plate concentrations of up to 5,000 μg/mL in the presence or absence of metabolic activation.

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

2010 ◽  
Vol 2010 ◽  
pp. 1-9 ◽  
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.

EFFECT OF NEONATAL ADMINISTRATION OF THYROXINE ON THE RATE OF SEBUM PRODUCTION IN RATS

1979 ◽  
Vol 83 (2) ◽  
pp. 199-203 ◽  
Author(s):  
YEE CHU TOH
Keyword(s):  
Normal Activity ◽  
Skin Surface ◽  
Postnatal Period ◽  
Female Rats ◽  
Sprague Dawley ◽  
Male And Female Rats ◽  
Sprague Dawley Rats ◽  
Sebum Production ◽  
Skin Surface Lipids ◽  
Neonatal Administration

Newborn Sprague–Dawley rats of both sexes were treated with 28 μg thyroxine (T4) daily for the first week of life. At the age of 80 days, the secretion rate of sebum was measured from the amount of skin-surface lipids extractable by acetone and which had been produced during 2 days. Treatment with such excess amounts of T4 during the early postnatal period significantly reduced the production of sebum in both male and female rats when compared with control rats and with rats deprived of food early in life. The thyroid, the pituitary gland, the testes and the seminal vesicles were significantly smaller but the weights of the ovaries and uteri remained relatively unaffected. There was a similar ratio of sex difference in the rate of sebum secretion irrespective of treatment. It is suggested that a reduction of sebaceous response in rats made thyrotoxic with large doses of T4 early in life was probably due to a decreased secretion of thyroid hormone which is required to maintain normal activity of the sebaceous glands.

ROLE OF THE GONADS IN THE REGULATION OF SEBACEOUS GLANDS IN RATS: COMPARISON OF THE EFFECTS OF CASTRATION AT AND AFTER BIRTH

1980 ◽  
Vol 85 (2) ◽  
pp. 261-265 ◽  
Author(s):  
YEE CHU TOH
Keyword(s):  
Skin Surface ◽  
Female Rats ◽  
Sprague Dawley ◽  
Sebaceous Glands ◽  
Male And Female Rats ◽  
Sprague Dawley Rats ◽  
Sequential Event ◽  
Sebum Production ◽  
Skin Surface Lipids

Sprague–Dawley rats were castrated either within 24 h of birth or at 4 weeks of age. Control animals were sham operated. Intact female rats were also included for comparison. Sebum production was assessed at 80 days of age by measuring the amount of skin-surface lipids that could be extracted with acetone and which had been produced during 2 days. The removal of the testes at birth reduced the activity of the sebaceous glands to a level more nearly approaching that seen in the female rats whereas castration at 4 weeks of age only partially decreased the rate of sebum secretion so that it was intermediate between the male and female rats. The weights of the pituitary gland, thyroid and adrenal glands increased after castration but there were no differences between rats castrated at birth and those castrated at 4 weeks of age except in the weight of the thyroid gland. It would appear that the role of the testes in the control of the activity of the sebaceous glands is a sequential event which has already started at birth.

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