scholarly journals Endocrine and Neurobehavioral Abnormalities Induced by Propofol Administered to Neonatal Rats

2014 ◽  
Vol 121 (5) ◽  
pp. 1010-1017 ◽  
Author(s):  
Sijie Tan ◽  
Changqing Xu ◽  
Wanting Zhu ◽  
Jesse Willis ◽  
Christoph N. Seubert ◽  
...  
Keyword(s):  
Prepulse Inhibition ◽  
Acoustic Startle ◽  
Serum Levels ◽  
Saline Group ◽  
Negative Control ◽  
Female Rats ◽  
Sprague Dawley ◽  
Ca1 Neurons ◽  
Male And Female Rats ◽  
Acid Type

Abstract Background: The authors studied whether neonatal propofol anesthesia affects development of the endocrine and neural systems. Methods: Sprague–Dawley rats were anesthetized using intraperitoneal propofol for 5 h on postnatal days (P) 4, 5, or 6. Pups that received either saline or intralipid, but not those in the negative control groups, were also maternally separated for 5 h. Serum levels of corticosterone were measured immediately after anesthesia and in adulthood after prepulse inhibition of acoustic startle testing (≥P80), followed by measurement of hippocampal neuronal activity. Results: Propofol acutely increased corticosterone levels to 146.6 ± 23.5 ng/ml (n = 6) versus 16.4 ± 3.5 ng/ml (n = 6) and 18.4 ± 3.2 ng/ml (n = 6) in saline- and intralipd-treated pups, respectively. In adulthood, the propofol group exhibited exacerbated endocrine responses to stress in a form of increased corticosterone levels (1,171.58 ± 149.17 ng/ml [n = 15] vs. 370.02 ± 36.01 ng/ml [n = 10] in the saline group). The propofol group had increased the frequency of miniature inhibitory postsynaptic currents in CA1 neurons of male and female rats, but reduced prepulse inhibition of startle was detected only in males. The Na+–K+–2Cl− cotransporter inhibitor bumetanide, administered to pups before propofol injection, alleviated long-term endocrine and prepulse inhibition abnormalities. Exogenous corticosterone, administered to naive pups, induced synaptic and endocrine but not prepulse inhibition effects, similar to those of propofol. Conclusion: Propofol-caused acute increases in corticosterone levels and γ-aminobutyric acid type A receptor–mediated excitation at the time of anesthesia may play mechanistic roles in development of exacerbated endocrine responses to stress and neurobehavioral abnormalities.

scholarly journals Robust and replicable measurement for prepulse inhibition of the acoustic startle response

2019 ◽  
Author(s):  
Eric A. Miller ◽  
David B. Kastner ◽  
Michael N. Grzybowski ◽  
Melinda R. Dwinell ◽  
Aron M. Geurts ◽  
...  
Keyword(s):  
Prepulse Inhibition ◽  
Startle Response ◽  
Acoustic Startle ◽  
Acoustic Startle Response ◽  
Experimental Manipulation ◽  
Female Rats ◽  
Psychiatric Disease ◽  
Wild Type ◽  
Sound Perception ◽  
Male And Female Rats

AbstractMeasuring animal behavior in the context of experimental manipulation is critical for modeling and understanding neuro-psychiatric disease. Prepulse inhibition of the acoustic startle response (PPI) is a behavioral paradigm used extensively for this purpose, but the results of PPI studies are often inconsistent. As a result, the utility of this metric remains uncertain. Here we deconstruct the phenomenon of PPI. We first confirm several limitations of the traditional PPI metric, including that the underlying startle response has a non-Gaussian distribution and that the traditional PPI metric changes with different stimulus condition. We then develop a novel model that reveals PPI to be a combination of the previously appreciated scaling of the startle response, as well as a scaling of sound perception. Using our model, we find no evidence for differences in PPI in a rat model of Fragile-X Syndrome (FXS) compared to wild-type controls. These results in the rat provide a reliable methodology that could be used to clarify inconsistent PPI results in mice and humans. In addition, we find robust differences between wild-type male and female rats. Our model allows us to understand the nature of these differences, and we find that both the startle-scaling and sound-scaling components of PPI are a function of the baseline startle response. Males and females differ specifically in the startle-scaling, but not the sound-scaling, component of PPI. These findings establish a robust experimental and analytical approach that has the potential to provide a consistent biomarker of brain function.

Effect of low doses of continuously administered catecholoestrogens on peripheral and central target organs

1981 ◽  
Vol 96 (4) ◽  
pp. 470-474 ◽  
Author(s):  
Peter Ball ◽  
Günter Emons ◽  
Ulrich Gethmann
Keyword(s):  
Serum Levels ◽  
Female Rats ◽  
Low Doses ◽  
Vaginal Opening ◽  
Uterine Weight ◽  
Central Target ◽  
Male And Female Rats ◽  
Target Organs ◽  
Uterine Growth ◽  
Lh Release

Abstract. Osmotic minipumps containing low doses of either 4-hydroxyoestradiol or 2-hydroxyoestradiol2) were sc implanted for 152 h (6⅓ day) into immature male and female rats. At the end of the test period the animals were killed and the uterine weight, the vaginal opening, the gonadotrophin serum levels and the gonadal weight monitored. The following results were obtained: 1) a significant increase in the uterine weight and a consistent vaginal opening were observed after 4-hydroxyoestradiol but not after 2-hydroxyoestradiol treatment, 2) LH-levels increased after 2-hydroxyoestradiol but not after 4-hydroxyoestradiol; the increase was, however, not significant, 3) FSH-levels and gonadal weights were lowered by 4-hydroxyoestradiol treatment in male animals only; 2-hydroxyoestradiol had no effect on FSH-levels in both sexes, 4) in no instance an antioestrogenic effect of either catecholoestrogen was observed. It is concluded that 4-hydroxyoestrogens — using the above paradigm — have a significant importance on uterine growth and vaginal opening but (on day 6) no role on LH-release, whereas 2-hydroxyoestrogens may increase LH levels (on day 6) but are nearly ineffective with respect to peripheral parameters.

scholarly journals Hydration with Mannitol and Dextrose May Promote Cisplatin-Induced Nephrotoxicity: Test of Five Protocols of Hydration during Cisplatin Therapy in Rat Models

2021 ◽  
Vol 2021 ◽  
pp. 1-9
Author(s):  
Mohammad-Sedigh Khosravi ◽  
Alireza Samimiat ◽  
Bahar Mazaheri ◽  
Farzaneh Ashrafi ◽  
Ardeshir Talebi ◽  
...  
Keyword(s):  
Tumor Therapy ◽  
Kidney Tissue ◽  
Serum Levels ◽  
Female Rats ◽  
Male Rats ◽  
Male And Female ◽  
Male And Female Rats ◽  
Female Wistar Rats ◽  
Solid Tumor Therapy ◽  
Cisplatin Therapy

Backgrounds. Cisplatin (CP) still is a novel choice for solid tumor therapy, but it is accompanied with the side effect of nephrotoxicity. Hydration may reduce the risk of CP-induced nephrotoxicity, while the issue is still challenging. In this study, five types of hydration protocols including saline, mannitol, dextrose saline, saline plus furosemide, and saline plus mannitol were examined in both sexes of rats during CP therapy. Methods. Seventy-six male and female Wistar rats in 14 groups of experiments were subjected to CP therapy, and five types of hydration protocols were implemented, and the induced nephrotoxicity was evaluated via biochemical markers, kidney function parameters, and pathology investigation. Results. Male and female rats had different responses to hydration protocol types. The higher mortality rate was seen in female rats that received mannitol or dextrose hydration types. In addition, the serum levels of blood urea nitrogen (BUN) and creatinine (Cr) and sodium excretion fraction (ENa%) increased and the clearance of Cr (ClCr) decreased significantly ( P < 0.05 ) in female rats hydrated with saline plus furosemide or mannitol plus saline-treated groups. The worsened condition in male rats is observed in the mannitol hydration group with a significant decrease of ClCr and significant increase of serum BUN and Cr and ENa% ( P < 0.05 ). The higher kidney tissue damage score (KTDS) in the mentioned groups verified the findings. Conclusion. Hydration with mannitol or dextrose promotes the risk of nephrotoxicity during CP therapy with more intensity on the female.

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 Antioxidant and Hepatoprotective Activity of a New Tablets Formulation fromTamarindus indicaL.

2016 ◽  
Vol 2016 ◽  
pp. 1-7 ◽  
Author(s):  
Jesús Rafael Rodriguez Amado ◽  
Ariadna Lafourcade Prada ◽  
Julio Cesar Escalona Arranz ◽  
Renato Pérez Rosés ◽  
Humberto Morris Quevedo ◽  
...  
Keyword(s):  
Lipid Peroxidation ◽  
Serum Levels ◽  
Hepatoprotective Activity ◽  
Negative Control ◽  
Diet Group ◽  
Control Group ◽  
Standard Diet ◽  
Tamarindus Indica ◽  
Sprague Dawley ◽  
Group I

Hepatotoxic chemicals damage liver cells primarily by producing reactive oxygen species. The decoction of the leaves ofTamarindus indicaL. is used for liver disorders. In this work we evaluated the hepatoprotective activity of a tablet formulation of this plant. Thirty-five Sprague Dawley rats were randomly divided into five groups (n=7). First group (I) is control group, fed with standard diet. Groups II to V (hepatotoxic groups) were subjected to a subcutaneous injection of CCl4(0.5 mL/kg). Group II was negative control, fed with standard diet; group III was subjected to administration of Silymarin 150 mg/kg and groups IV and V were treated with tablets in dose of 100 mg/kg and 200 mg/kg, respectively. Lipid peroxidation and the activity of superoxide dismutase, catalase, and reduced glutathione were evaluated. Serum levels of alanine aminotransferase, aspartate aminotransferase, gamma-glutamine transferase, alkaline phosphatase, and a lipid profile were evaluated too. The tablets inhibit lipid peroxidation. The redox balance (SOD-CAT-GSH) remains normal in the experimental groups treated with tablets. The liver function using dose of 200 mg/kg of tablets was better than the other experimental groups. These results justify, scientifically, the ethnobotanical use of the leaves ofTamarindus indicaL.

DIFFERENTIAL EFFECTS OF CASTRATION ON LH AND FSH SECRETION IN MALE AND FEMALE RATS

1975 ◽  
Vol 78 (4) ◽  
pp. 683-688 ◽  
Author(s):  
M. Zanisi ◽  
L. Martini
Keyword(s):  
Serum Levels ◽  
Female Rats ◽  
Delayed Response ◽  
Male And Female ◽  
Differential Effects ◽  
Male And Female Rats ◽  
Normal Controls

ABSTRACT Serum levels of LH and of FSH have been measured using specific radioimmunological procedures in normal controls and in male and female rats submitted to castration 1, 2, 7, 14, 21, 28 and 35 days before. Gonadectomy is followed by a rapid increase of serum levels of LH in males, and by a delayed response in females. The responses of serum FSH to castration are quantitatively and qualitatively similar in the two sexes. Both in males and in females an elevation of serum FSH levels is already present 1 day after the operation. Serum FSH continues to rise, between post-castration days 1 and 7 with a rather rapid slope, and at later intervals with a smoother progression.

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 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.

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