Opposite effects of high- and low-dose di-(2-ethylhexyl) phthalate (DEHP) exposure on puberty onset, oestrous cycle regularity and hypothalamic kisspeptin expression in female rats

2020 ◽  
Vol 32 (6) ◽  
pp. 610 ◽  
Author(s):  
Zhen Yu ◽  
Fan Wang ◽  
Junyong Han ◽  
Rongmei Lu ◽  
Qian Li ◽  
...  
Keyword(s):  
Low Dose ◽  
Corn Oil ◽  
Oestrous Cycle ◽  
Female Rats ◽  
High Dose ◽  
Cycle Duration ◽  
Sprague Dawley ◽  
Puberty Onset ◽  
Ethylhexyl Phthalate ◽  
Dehp Exposure

Di-(2-ethylhexyl) phthalate (DEHP) is ubiquitous in the environment and has been proposed to lead to reproductive disruption. In this study, we systematically investigated the effects of different doses of DEHP exposure on female hypothalamic–pituitary–gonadal axis development. Female Sprague–Dawley rats were gavaged with vehicle (corn oil) or DEHP (5 or 500mgkg–1 day–1) during postnatal Days (PNDs) 22–28 or PNDs 22–70. Results demonstrated that the low and high doses of DEHP exerted opposite effects on puberty onset, circulating luteinising hormone, serum oestradiol and progesterone levels, with the low dose (5mgkg–1) promoting and the high dose (500mgkg–1) inhibiting these parameters. Significant dose-related differences were also found in the D500 group with longer oestrous cycle duration, lower ovarian/bodyweight ratio, fewer corpus lutea and more abnormal ovarian stromal tissue in comparison with the oil or D5 groups. Molecular data showed that the hypothalamic Kiss1 mRNA expression in the anteroventral periventricular but not in the arcuate nucleus significantly decreased in the D500 rats and increased in the D5 rats relative to the rats in the oil group. These findings suggested that the kisspeptin system is a potential target for DEHP to disrupt reproductive development and function.

Impaired follicular development and endocrine disorders in female rats by prepubertal exposure to toxic doses of cadmium

2020 ◽  
Vol 36 (2) ◽  
pp. 63-75
Author(s):  
Saman Saedi ◽  
Mohammad Reza Jafarzadeh Shirazi ◽  
Mohammad Javad Zamiri ◽  
Mehdi Totonchi ◽  
Mohammad Dadpasand ◽  
...  
Keyword(s):  
Steroid Hormones ◽  
Endocrine System ◽  
Follicular Development ◽  
Female Rats ◽  
High Dose ◽  
Endocrine Disorders ◽  
Sprague Dawley ◽  
Sprague Dawley Rats ◽  
Puberty Onset ◽  
Different Doses

Cadmium (Cd) has been associated with several physiological problems including reproductive and endocrine system dysfunction resulting in temporary infertility. The principal objective of this project was to investigate the effects of prepubertal exposure to toxic doses of Cd on puberty onset, the endocrine system, and follicular development. For this purpose, 16 female Sprague-Dawley rats weaned on postnatal day (PND) 21 were randomly divided into 4 groups ( n = 4 per group). The treatments were as follows: 0, 25, 50, and 75 mg/kg/day of cadmium chloride (CdCl2) by oral gavage from PND 21 to observation of first vaginal opening (VO). The results demonstrated that prepubertal exposure to different doses of CdCl2 delays the age of VO, first diestrus, and first proestrus via altering the concentrations of estradiol and progesterone. The low level of these steroid hormones contributed to lower differentiation and maturation of follicles and it finally led to reduced ovarian reservoir of follicles and impaired follicular development. The number of atretic follicles and secondary follicles with premature cavity increased in rats that received a high dose of CdCl2, whereas the number of secondary follicles and corpora luteum decreased in the same circumstances. Taken together, these data suggest that prepubertal exposure to toxic doses of Cd delays the onset of puberty via disorderliness in the concentration of steroid hormones and reduces the ovarian reservoir of follicles, as well as folliculogenesis.

Toxicokinetics of cis- and trans-Permethrin: Influence of Isomer, Maturation, and Sex

2019 ◽  
Vol 174 (1) ◽  
pp. 25-37 ◽  
Author(s):  
Jing Pang ◽  
Tanzir Mortuza ◽  
Catherine A White ◽  
Srinavasa Muralidhara ◽  
Brian S Cummings ◽  
...  
Keyword(s):  
Corn Oil ◽  
Brain Area ◽  
Age Groups ◽  
Female Rats ◽  
High Dose ◽  
Sprague Dawley ◽  
Male And Female Rats ◽  
High Doses ◽  
Cis And Trans ◽  
Elevated Exposure

Abstract Permethrin exposure of children and adults is widespread in many populations, but knowledge of its relative toxicokinetics (TK) and health risks in immature age groups is lacking. Studies were conducted in rats to determine the influence of immaturity and sex (on plasma and target organ dosimetry of each of the insecticide’s 2 isomers, cis- and trans-permethrin [CIS and TRANS]). Postnatal day 15, 21, and 90 (adult), Sprague Dawley rats were orally administered a graduated series of doses of CIS and TRANS in corn oil. Serial sacrifices were conducted over 24 h to obtain plasma, brain, liver, skeletal muscle, and fat profiles of CIS and TRANS. Levels of TRANS decreased relatively rapidly, despite administration of relatively high doses. Concentrations of each isomer in plasma, brain, and other tissues monitored were inversely proportional to the animals’ age. The youngest pups exhibited 4-fold higher plasma and brain area under the curves than did adults. Little difference was observed in the TK of CIS or TRANS between adult male and female rats, other than higher initial plasma and liver CIS levels in females. Elevated exposure of the immature brain appears to be instrumental in increased susceptibility to the acute neurotoxicity of high-dose permethrin (Cantalamessa [1993]), but it remains to be established whether age-dependent TK is relevant to long-term, low-level risks.

scholarly journals Pharmacokinetic and Histopathologic Study of an Extended-Release, Injectable Formulation of Buprenorphine in Sprague–Dawley Rats

2021 ◽  
Author(s):  
Barry L Levinson ◽  
Steven L Leary ◽  
Bev J Bassett ◽  
Charles J Cook ◽  
Gregory S Gorman ◽  
...  
Keyword(s):  
Dose Group ◽  
Extended Release ◽  
Low Dose ◽  
Test Group ◽  
Female Rats ◽  
Male Rats ◽  
High Dose ◽  
Sprague Dawley ◽  
Time Points ◽  
Sprague Dawley Rats

A novel buprenorphine (BUP) extended-release formulation (BUP-XR) produced as a lipid-encapsulated, low viscosity BUP suspension for SC injection to control pain was evaluated for pharmacokinetics and safety in Sprague–Dawley rats given either 0.65 mg/kg (low dose) or 1.30 mg/kg (high dose). The 2 dosage groups each contained 6 male and 6 female rats to determine whether BUP-XR behaved differently in male or female animals. Blood samples were obtained from each animal before BUP-XR administration and at 6, 24, 48, 72, 96, and 168 h after administration. For necropsy and injection-sitehistopathology evaluation, 3 animals of each sex from each test group were euthanized on day 8, with the remaining animals euthanized on day 15. Mean plasma BUP concentration peaked from 6 to 24 h in all test groups, then declined in a linear fashion. Quantifiable plasma BUP was measured in all male rats at all time points except for one low dose group sample taken at 168 h. Female rats had quantifiable plasma BUP at all time points except for 1 low dose group sample at 72 and 96 h, and 2 low dose group samples at 168 h. The low dose groups, whether male or female, had lower mean plasma BUP levels at all time points as compared with their high dose counterparts, and female rats had lower mean plasma BUP levels than male rats at all time points. Results indicate that a single BUP-XR dose at either dose concentration can reliably provide plasma levels of BUP reported in the literature to be therapeutically relevant for up to 72 h, although lower plasma BUP levels can be anticipated in female rats compared with male counterparts. Mild to moderate injection-site granulomatous inflammation was observed in 6 of 12 rats in the low dose group and 7 of 12 in the high dose group. This reaction is characteristic of lipid material designed to persist in situ.

NEW DATA CONCERNING THE ROLE PLAYED BY PROGESTERONE IN THE CONTROL OF FOLLICULAR GROWTH IN THE RAT

1974 ◽  
Vol 75 (3) ◽  
pp. 569-578 ◽  
Author(s):  
G. Buffler ◽  
S. Roser
Keyword(s):  
Wistar Rats ◽  
Venous Blood ◽  
Oestrous Cycle ◽  
Female Rats ◽  
Cycle Duration ◽  
Follicular Growth ◽  
The Third ◽  
Female Wistar Rats

ABSTRACT The mechanisms involved in the prolongation of the oestrous cycle following LH administration were studied in 4-day cyclic female Wistar rats. In females injected with LH on the morning of dioestrus I there was an increase in ovarian venous blood progesterone as compared with non-injected animals. In both LH-treated females, and those injected with progesterone on the morning of dioestrus I, a slowing up in follicular growth was observed from the afternoon of dioestrus I. The size of follicles greater than 400 urn present in LH or progesterone injected animals on the third day of cycle was similar to the size reached by the same range of follicles in non-injected animals on the second day of the cycle. Hence, the increase in endogenous ovarian progesterone elicited by LH was considered as the cause of the slowing up of follicular growth and therefore of the lengthening of the oestrous cycle duration in female rats injected with LH at the beginning of 4-day cycle.

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.

Ultrastructural changes of Basolateral Amygdaloid nuclei in the Sprague Dawley rats brain following exposure to naphthalene balls

2021 ◽  
Vol 12 (2) ◽  
pp. 1272-1275
Author(s):  
Angu Bala Ganesh K S V ◽  
Sujeet Shekhar Sinha ◽  
Kesavi Durairaj ◽  
Abdul Sahabudeen K
Keyword(s):  
Structural Changes ◽  
Corn Oil ◽  
Chromatin Condensation ◽  
Ultrastructural Changes ◽  
High Dose ◽  
Model Group ◽  
Sprague Dawley ◽  
Sprague Dawley Rats ◽  
The Brain ◽  
Amygdaloid Nuclei

Naphthalene is a bicyclic aromatic constituent commonly used in different domestic and marketable applications comprising soil fumigants, lavatory scent disks and mothballs. Accidentally, workers, children and animals are exposed to naphthalene mothballs, so there is a need to study the pathology behind this chemical toxicity. The current study was carried out to assess the ultra structural changes of basolateral amygdaloid nuclei in the Sprague Dawley rats brain in association to naphthalene toxicity. The toxicity model group was administered with naphthalene (200 and 400mg) using corn oil as a vehicle for 28 days. The post delayed toxicity of naphthalene high dose ingestion was also assessed in rats. After the experimental period, the brain tissue was processed to observe the ultra structural changes using a transmission electron microscope. The alterations in cell organelles, nuclei damage, mitochondrial swelling, chromatin condensation suggested naphthalene induced damage in the neurons of the basolateral amygdala of the brain in the toxicity model group. These experimental trials provide information about the alert of mothball usage in the home and identify risks linked with accidental exposure and misuse.

Male gender increases sensitivity to renal injury in response to cholesterol loading

2003 ◽  
Vol 284 (4) ◽  
pp. F718-F726 ◽  
Author(s):  
Diana M. Attia ◽  
Roel Goldschmeding ◽  
Mahmoud A. Attia ◽  
Peter Boer ◽  
Hein A. Koomans ◽  
...  
Keyword(s):  
Renal Injury ◽  
Low Dose ◽  
Plasma Cholesterol ◽  
A Priori ◽  
No Synthase ◽  
Male Gender ◽  
Female Rats ◽  
Male Rats ◽  
High Dose ◽  
Cholesterol Feeding

Males are at greater risk for renal injury than females. This may relate to nitric oxide (NO) availability, because female rats have higher renal endothelial NO synthase (NOS) levels. Previously, our laboratory found susceptibility to proteinuria induced by NOS inhibition in male compared with female rats. Dyslipidemia and hypercholesterolemia dose dependently decreased renal NOS activity and caused renal injury in female rats. We hypothesized that exposure of male rats to hypercholesterolemia would lead to more renal injury in male than in female rats due to an a priori lower renal NO system. Female and male rats were fed no, low-dose, or high-dose cholesterol for 24 wk. Cholesterol feeding dose dependently increased proteinuria in both female and male rats, but male rats developed more proteinuria at similar plasma cholesterol ( P < 0.001). Control males had lower renal NOS activity than control females (4.44 ± 0.18 vs. 7.46 ± 0.37 pmol · min−1 · mg protein−1; P < 0.05), and cholesterol feeding decreased renal NOS activity in males and in females ( P < 0.05). Cholesterol-fed males developed significantly more vascular, glomerular, and tubulointerstitial monocyte/macrophage influx and injury than females. Thus under baseline conditions, male rats have lower renal NOS activity than female rats. This may explain why male rats are more sensitive to renal injury by factors that decrease NO availability, such as hypercholesterolemia.

Ferulic Acid Dose Effect on Pharmacokinetics of Glimepiride and its Metabolite Hydroxy Glimepiride in Rats

2021 ◽  
Vol 17 ◽  
Author(s):  
Yuxian Lin ◽  
Faxin Sun ◽  
Jinlai Liu ◽  
Qinghua Weng ◽  
Lijun Jin ◽  
...  
Keyword(s):  
Ferulic Acid ◽  
Low Dose ◽  
Dose Effect ◽  
High Dose ◽  
Intragastric Administration ◽  
Healthy Male ◽  
Sprague Dawley ◽  
Sd Rats ◽  
High Dose Treatment ◽  
Significant Difference

Background: To mitigate diabetes and its complications in cardiovascular diseases, the antidiabetic agent glimepiride is usually administered with ferulic acid concomitantly in clinics. However, both drugs are prone to be metabolized partly by CYP2C9, thus they have the potential drug-drug interaction affecting the safety and efficacy. Objective: This project aimed to evaluate the pharmacokinetic (PK) effects of ferulic acid (FA) on glimepiride (GLM) and its metabolite hydroxy glimepiride (OH-GLM) in plasma by using the HPLC-MS/MS method. Methods: Healthy male Sprague Dawley (SD) rats were randomly divided into three groups. They received intragastric administration of 0.5% sodium carboxymethyl cellulose (CMC), low-dose FA (20 mg•kg-1), and high-dose FA (40 mg•kg-1) for 8 days, respectively. Rats were given 0.5% sodium CMC or FA on the last day and then uniformly given 1.0 mg•kg-1 glimepiride by gavage. Blood samples were obtained from retro-orbital plexus at the time points of 0.167, 0.5, 1, 2, 3, 4, 6, 8, 10, 12, and 24 h after administration. Plasma samples were analyzed for GLM and its metabolite OH-GLM on an HPLC-MS/MS system. Results: No statistically significant difference was found in the effect of low-dose FA on the pharmacokinetics of GLM. High-dose FA significantly decreased Cmax of GLM by 30.05% and CLz/F of OH-GLM by 47.45%. It also increased Tmax and t1/2z of GLM by 95.87% and 140.00%. Conclusion: Low-dose FA did not alter GLM metabolism, while high-dose treatment of FA caused pharmacokinetics interaction with GLM in rats.

Investigation of the effects of bisphenol-A exposure on lymphoid system in prenatal stage

2020 ◽  
Vol 36 (7) ◽  
pp. 502-513
Author(s):  
Işil Aydemir ◽  
Caner Özbey ◽  
Oktay Özkan ◽  
Şadiye Kum ◽  
Mehmet İbrahim Tuğlu
Keyword(s):  
Lymph Node ◽  
Bisphenol A ◽  
Tissue Damage ◽  
Corn Oil ◽  
Histopathological Examination ◽  
Female Rats ◽  
Male Rats ◽  
High Dose ◽  
Organ Function ◽  
Pregnant Rats

Bisphenol-A (BPA) used in the production of plastic materials is a temperature-soluble agent. It also has a steroid hormone-like activity; therefore, it poses a danger to human health. In our study, we aimed to investigate the effects of BPA on lymph node and spleen in male rats exposed to this agent during prenatal stage. The pregnant female rats were divided into four groups: control, sham, low dose (300 µg/kg BPA), and high dose (900 µg/kg BPA). BPA was dissolved in 1 mL of corn oil and administered to the pregnant rats every day during pregnancy. On the 21st and 45th day after the birth, male rats’ lymph node and spleen samples were taken and histopathological examination was performed. Samples were stained with hematoxylin and eosin to determine the general histological appearance, and with CD3 and CD20 immunohistochemically. The results of staining were evaluated by H-score, and statistical analysis was performed. In the samples, BPA applications were not found to cause significant tissue damage. But there was a significant decrease in the immunoreactivities of CD3 and CD20 after BPA applications in both 21st and 45th day samples. After high dose BPA administration, decreased CD3 immunoreactivity was statistically significant. It is thought that BPA does not cause histologically significant tissue damage, but it may impair organ function at cellular level. The investigation of molecules involved in organ function will be useful in revealing the mechanisms that will cause dysfunction.

The arterial depressor response to chronic low-dose angiotensin II infusion in female rats is estrogen dependent

2012 ◽  
Vol 302 (1) ◽  
pp. R159-R165 ◽  
Author(s):  
Amanda K. Sampson ◽  
Lucinda M. Hilliard ◽  
Karen M. Moritz ◽  
Merlin C. Thomas ◽  
Chris Tikellis ◽  
...  
Keyword(s):  
Angiotensin Ii ◽  
Arterial Pressure ◽  
Low Dose ◽  
Renin Angiotensin System ◽  
Female Rats ◽  
Ang Ii ◽  
Pressure Regulation ◽  
Estrogen Replacement ◽  
Sprague Dawley ◽  
Arterial Pressure Regulation

The complex role of the renin-angiotensin-system (RAS) in arterial pressure regulation has been well documented. Recently, we demonstrated that chronic low-dose angiotensin II (ANG II) infusion decreases arterial pressure in female rats via an AT2R-mediated mechanism. Estrogen can differentially regulate components of the RAS and is known to influence arterial pressure regulation. We hypothesized that AT2R-mediated depressor effects evident in females were estrogen dependent and thus would be abolished by ovariectomy and restored by estrogen replacement. Female Sprague-Dawley rats underwent ovariectomy or sham surgery and were treated with 17β-estradiol or placebo. Mean arterial pressure (MAP) was measured via telemetry in response to a 2-wk infusion of ANG II (50 ng·kg−1·min−1 sc) or saline. MAP significantly decreased in females treated with ANG II (−10 ± 2 mmHg), a response that was abolished by ovariectomy (+4 ± 2 mmHg) and restored with estrogen replacement (−6 ± 2 mmHg). Cardiac and renal gene expression of components of the RAS was differentially regulated by estrogen, such that overall, estrogen shifted the balance of the RAS toward the vasodilatory axis. In conclusion, estrogen-dependent mechanisms offset the vasopressor actions of ANG II by enhancing RAS vasodilator pathways in females. This highlights the potential for these vasodilator pathways as therapeutic targets, particularly in women.

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