High-dose etoposide formulations do not saturate intestinal P-glycoprotein: Development, stability, and pharmacokinetics in Sprague-Dawley rats

Postpartum depression affects 15% of women.Channa striatus, a freshwater fish, is consumed in local Malay population as a rejuvenating diet during postpartum period. This study evaluated the antidepressant-like effect of lipid extract ofC. striatusfillet and its mechanism of action in female Sprague-Dawley rats in postpartum model of depression. The rats were ovariectomized and treated with high dose of progesterone and estradiol benzoate for 23 days to have hormone-simulated pregnancy. The day 24 and afterwards were considered as the postpartum period. During the postpartum period, lipid extract was administered at 125, 250, and 500 mg/kg through intraperitoneal route for 15 days. Fluoxetine (10 mg/kg) was used as the positive control. On postpartum day 15, the animals were tested in forced swimming test (FST) and open field test (OFT) followed by biochemical analysis. Withdrawal of hormone administration during the postpartum period induced depressive-like behavior in FST. Administration of lipid extract reversed that depressive-like behavior at 125, 250, and 500 mg/kg in FST. In OFT, it decreased the exploratory activity. The mechanism of the antidepressant-like effect may be mediated through the decrease in plasma corticosterone, increase in plasma oxytocin, and decrease in nuclear factor-kappa B in prefrontal cortex of rats.

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

International Journal of Research in Pharmaceutical Sciences ◽

10.26452/ijrps.v12i2.4676 ◽

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.

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Erythropoietin Produces a Dual Effect on Carotid Body Chemoreception in Male Rats

Frontiers in Pharmacology ◽

10.3389/fphar.2021.727326 ◽

2021 ◽

Vol 12 ◽

Author(s):

Christian Arias-Reyes ◽

Sofien Laouafa ◽

Natalia Zubieta-DeUrioste ◽

Vincent Joseph ◽

Aida Bairam ◽

...

Keyword(s):

Carotid Body ◽

No Synthase ◽

Male Rats ◽

High Dose ◽

No Production ◽

Sprague Dawley ◽

En Bloc ◽

No Synthase Inhibitor ◽

Sprague Dawley Rats ◽

Synthase Inhibitor

Erythropoietin (EPO) regulates respiration under conditions of normoxia and hypoxia through interaction with the respiratory centers of the brainstem. Here we investigate the dose-dependent impact of EPO in the CB response to hypoxia and hypercapnia. We show, in isolated “en bloc” carotid body (CB) preparations containing the carotid sinus nerve (CSN) from adult male Sprague Dawley rats, that EPO acts as a stimulator of CSN activity in response to hypoxia at concentrations below 0.5 IU/ml. Under hypercapnic conditions, EPO did not influence the CSN response. EPO concentrations above 0.5 IU/ml decreased the response of the CSN to both hypoxia and hypercapnia, reaching complete inhibition at 2 IU/ml. The inhibitory action of high-dose EPO on the CSN activity might result from an increase in nitric oxide (NO) production. Accordingly, CB preparations were incubated with 2 IU/ml EPO and the unspecific NO synthase inhibitor (L-NAME), or the neuronal-specific NO synthase inhibitor (7NI). Both NO inhibitors fully restored the CSN activity in response to hypoxia and hypercapnia in presence of EPO. Our results show that EPO activates the CB response to hypoxia when its concentration does not exceed the threshold at which NO inhibitors masks EPO’s action.

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Toxicity associated with ingestion of a polyacrylic acid hydrogel dog pad

Journal of Veterinary Diagnostic Investigation ◽

10.1177/1040638718782583 ◽

2018 ◽

Vol 30 (5) ◽

pp. 708-714 ◽

Cited By ~ 1

Author(s):

David C. Dorman ◽

Melanie L. Foster ◽

Brooke Olesnevich ◽

Brad Bolon ◽

Aude Castel ◽

...

Keyword(s):

Motor Activity ◽

Polyacrylic Acid ◽

Muscle Tone ◽

Clinical Signs ◽

High Dose ◽

Sprague Dawley ◽

Sprague Dawley Rats ◽

Before And After ◽

Acute Neurotoxicity ◽

Disposable Diapers

Superabsorbent sodium polyacrylate polymeric hydrogels that retain large amounts of liquids are used in disposable diapers, sanitary napkins, and other applications. These polymers are generally considered “nontoxic” with acute oral median lethal doses (LD50) >5 g/kg. Despite this favorable toxicity profile, we identified a novel toxic syndrome in dogs and rats following the ingestion of a commercial dog pad composed primarily of a polyacrylic acid hydrogel. Inappropriate mentation, cerebellar ataxia, vomiting, and intention tremors were observed within 24 h after the ingestion of up to 15.7 g/kg of the hydrogel by an adult, castrated male Australian Shepherd mix. These observations prompted an experimental study in rats to further characterize the toxicity of the hydrogel. Adult, female Sprague Dawley rats ( n = 9) were assessed before and after hydrogel ingestion (2.6–19.2 g/kg over 4 h) using a functional observation battery and spontaneous motor activity. Clinical signs consistent with neurotoxicity emerged in rats as early as 2 h after the end of hydrogel exposure, including decreased activity in an open field, hunched posture, gait changes, reduced reaction to handling, decreased muscle tone, and abnormal surface righting. Hydrogel-exposed rats also had reduced motor activity when compared with pre-exposure baseline data. Rats that ingested the hydrogel did not develop nervous system lesions. These findings support the conclusion that some pet pad hydrogel products can induce acute neurotoxicity in animals under high-dose exposure conditions.

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

Toxicology and Industrial Health ◽

10.1177/0748233720912060 ◽

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.

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Safety Assessment of Ubiquinol Acetate: Subchronic Toxicity and Genotoxicity Studies

Journal of Toxicology ◽

10.1155/2019/3680757 ◽

2019 ◽

Vol 2019 ◽

pp. 1-25

Author(s):

Gajanan Deshmukh ◽

Suresh B. Venkataramaiah ◽

Chandrashekar M. Doreswamy ◽

Mohan C. Umesh ◽

Rajesh B. Subbanna ◽

...

Keyword(s):

Biologically Active ◽

High Dose ◽

Sprague Dawley ◽

Subchronic Toxicity ◽

Sprague Dawley Rats ◽

Adverse Effect Level ◽

Effect Level ◽

Endogenous Antioxidant ◽

In Vitro Genotoxicity

Coenzyme Q10 (CoQ10) is a lipid soluble, endogenous antioxidant present at highest levels in the heart followed by the kidney and liver. The reduced CoQ10 ubiquinol is well known for its chemical instability and low bioavailability. The present study was designed to synthesize ubiquinol acetate, which is more stable and biologically active, and further evaluate its safety and genotoxic potential. Synthesized ubiquinol acetate showed better stability than that of ubiquinol at the end of 3 months. In vitro genotoxicity studies (AMES test, in vitro micronucleus and chromosomal aberration) showed ubiquinol acetate as nongenotoxic with no clastogenic or aneugenic effects at high dose of 5000 and 62.5 μg/mL, respectively. In subchronic toxicity study, ubiquinol acetate was administered orally to Sprague Dawley rats at 150, 300, and 600 mg/kg/day for 90 days. No treatment related adverse effects were observed in males at 600 mg/kg/day; however, females showed treatment related increase in AST and ALT with small focal irregular white-yellow spots in liver on gross necropsy examination. Histopathological evaluation revealed hepatocellular necrosis in high dose females which was considered as adverse. Based on the results, the No-Observed-Adverse-Effect Level (NOAEL) of ubiquinol acetate in males and females was determined as 600 and 300 mg/kg/day, respectively.

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Dexmedetomidine Pretreatment Attenuates Kidney Injury and Oxidative Stress during Orthotopic Autologous Liver Transplantation in Rats

Oxidative Medicine and Cellular Longevity ◽

10.1155/2016/4675817 ◽

2016 ◽

Vol 2016 ◽

pp. 1-10 ◽

Cited By ~ 10

Author(s):

Xiaofang Yu ◽

Xinjin Chi ◽

Shan Wu ◽

Yi Jin ◽

Hui Yao ◽

...

Keyword(s):

Liver Transplantation ◽

Kidney Injury ◽

Receptor Blocker ◽

High Dose ◽

Related Factor ◽

Protective Effects ◽

Sprague Dawley ◽

Sprague Dawley Rats ◽

S Model ◽

Autologous Liver

This paper aims to explore whether pretreatment with dexmedetomidine (Dex) has antioxidative and renal protective effects during orthotopic autologous liver transplantation (OALT) and its impact on nuclear factor erythroid 2-related factor 2 (Nrf2) activation. Sprague-Dawley rats were randomized into groups that include sham-operated (group S), model (group M), low dose Dex (group D1), high dose Dex (group D2), atipamezole (a nonspecificα2receptor blocker) + high dose Dex (group B1), ARC239 (a specificα2B/creceptor blocker) + high dose Dex (group B2), and BRL-44408 (a specificα2Areceptor blocker) + high dose Dex (group B3). Then histopathologic examination of the kidneys and measurement of renal function, the renal Nrf2 protein expression, and oxidants and antioxidants were performed 8 hours after OALT. We found that pretreatment with Dex activated Nrf2 in glomerular cells and upregulated antioxidants but reduced oxidants (allP<0.01, group D2 versus group M). Atipamezole and BRL-44408, but not ARC239, reversed these protective effects. In conclusion, pretreatment with Dex activates Nrf2 throughα2Areceptor, increases the antioxidant levels, and attenuates renal injury during OALT.

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ANF secretion and renal responses to volume expansion with equilibrated blood

AJP Renal Physiology ◽

10.1152/ajprenal.1988.255.5.f936 ◽

1988 ◽

Vol 255 (5) ◽

pp. F936-F943 ◽

Cited By ~ 4

Author(s):

R. V. Paul ◽

T. Ferguson ◽

L. G. Navar

Keyword(s):

Blood Volume ◽

Sodium Excretion ◽

Volume Expansion ◽

Fractional Excretion ◽

High Dose ◽

Sprague Dawley ◽

Blood Volume Expansion ◽

Step Procedure ◽

Sprague Dawley Rats ◽

Fractional Excretion Of Sodium

To evaluate the role of atrial natriuretic factor (ANF) in the renal response to acute blood volume expansion without hemodilution, a reservoir syringe filled with donor rat blood was connected to the femoral artery and vein of anesthetized Sprague-Dawley rats to allow rapid equilibration of the reservoir with the intravascular blood. Volume expansion with blood from the reservoir in two steps (of 1 and 1.5% body wt, separated by 1 h, n = 5 rats) produced a mean peak increase in plasma immunoreactive ANF from 99 +/- 21 to 1,310 +/- 230 pg/ml (P less than 0.001); plasma ANF levels throughout these experiments correlated significantly with simultaneously measured urine flow (r = 0.74, P less than 0.005) and sodium excretion (r = 0.65, P less than 0.005). Another group (n = 7) underwent the same two-step procedure; after the second volume expansion, high-dose atriopeptin III infusion (0.4 microgram.kg-1.min-1 did not further increase fractional excretion of sodium (3.17 +/- 0.27 to 2.50 + 0.39%, P = NS). In another group (n = 9 rats), the same dose of atriopeptin III was started before any blood volume expansion. After the resulting hypotension was corrected by restoration of blood volume, an additional 1.5% body weight blood volume expansion did not further augment sodium excretion. We conclude that the diuresis and natriuresis, which occur in response to volume expansion without hemodilution, rise and fall in parallel with immunoreactive ANF in the plasma, and that ANF and acute blood volume expansion act on the kidney through a similar, saturable mechanism.

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Toxicological Features ofCatha edulis(Khat) on Livers and Kidneys of Male and Female Sprague-Dawley Rats: A Subchronic Study

Evidence-based Complementary and Alternative Medicine ◽

10.1155/2012/829401 ◽

2012 ◽

Vol 2012 ◽

pp. 1-11 ◽

Cited By ~ 13

Author(s):

Abdulsamad Alsalahi ◽

Mahmood Ameen Abdulla ◽

Mohammed Al-Mamary ◽

Mohamed Ibrahim Noordin ◽

Siddig Ibrahim Abdelwahab ◽

...

Keyword(s):

Male Rats ◽

High Dose ◽

Sprague Dawley ◽

Catha Edulis ◽

Male And Female ◽

Sd Rats ◽

Sprague Dawley Rats ◽

Serum Aspartate Aminotransferase ◽

Liver And Kidney ◽

Kg Medium

Hepato- and nephrotoxicity of Khat consumption (Catha edulisForskal) have been evoked. Therefore, this study was conducted to evaluate such possible hepatorenal toxicity in female and male Sprague-Dawley rats (SD rats) focusing primarily on liver and kidney. In addition, female and male rats were investigated separately. Accordingly, forty-eight SD-rats (100–120 g) were distributed randomly into four groups of males and female (n=12). Normal controls (NCs) received distilled water, whereas test groups received 500 mg/kg (low dose (LD)), 1000 mg/kg (medium dose (MD)), or 2000 mg/kg (high dose (HD)) of crude extract ofCatha edulisorally for 4 weeks. Then, physical, biochemical, hematological, and histological parameters were analyzed. Results in Khat-fed rats showed hepatic enlargement, abnormal findings in serum aspartate aminotransferase (AST), and alkaline phosphatase (ALP) of male and female SD-rats and serum albumin (A) and serum creatinine (Cr) of female as compared to controls. In addition, histopathological abnormalities confirmed hepatic and renal toxicities of Khat that were related to heavy Khat consumption. In summary, Khat could be associated with hepatic hypertrophy and hepatotoxicity in male and female SD-rats and nephrotoxicity only in female SD-rats.

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Chronic Ingestion of High Dosed Phikud Navakot Extraction Induces Mesangiolysis in Rats with Alteration of AQP1 and Hsp60 Expressions

BioMed Research International ◽

10.1155/2015/462387 ◽

2015 ◽

Vol 2015 ◽

pp. 1-11 ◽

Cited By ~ 7

Author(s):

Kanchana Kengkoom ◽

Sumate Ampawong

Keyword(s):

Vascular Function ◽

Cell Damage ◽

Protective Role ◽

Histopathological Study ◽

High Dose ◽

Sprague Dawley ◽

Endothelial Lining ◽

Sprague Dawley Rats ◽

Aqp1 Expression ◽

Chronic Ingestion

Phikud Navakot (PN) is commonly used in Thai traditional medicine for alleviation of cardiovascular and cerebrovascular symptoms; however little is known about the chronic toxicity effects of the extracts from the herbs in PN. Repeated extraction doses of 10, 100, and 1,000 mg/kg/day were randomly administered to both male and female Sprague Dawley rats for 12 months. Histopathological study revealed that mesangiolysis was predominately found at the highest dose. Aquaporin 1 (AQP1) expression in the mesangiolytic glomeruli was significantly lower than in the intact glomeruli. This may be relevant to an imbalance of vascular function manifested by AQP1 alteration. In the mesangiolytic glomeruli, 60 kDa heat shock protein (Hsp60) was significantly upregulated on the endothelial lining cells of aneurysm and vascular cyst. Hsp60 increase may be related to endothelial cell damage due to its intracellular protective role. Blood urea nitrogen and creatinine levels remained within their normal range indicating well-functioning renal reserve function. In conclusion, high dosed PN may affect the endothelium leading to inability of vascular permeability and consequence to mesangiolysis. Our results suggest that only a high dose of chronic oral administration of PN is relatively toxic in association with mesangiolysis. The NOAEL was determined to be 100 mg/kg/day.

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