scholarly journals Subacute Intramuscular Toxicity of the Acetylcholinesterase Reactivating Agent HI-6 in Rats and Dogs

1993 ◽  
Vol 12 (2) ◽  
pp. 185-193 ◽  
Author(s):  
Barry S. Levine ◽  
Michael J. Tomlinson
Keyword(s):  
Injection Site ◽  
Creatine Kinase Activity ◽  
High Dose ◽  
Sprague Dawley ◽  
Hi 6 ◽  
Sprague Dawley Rats ◽  
High Doses ◽  
Hematology Parameters ◽  
Dose Levels ◽  
Dose Injection

Studies herein describe the toxicity of HI-6 in Sprague-Dawley rats and Beagle dogs following i.m. injection for 14 days. Dose levels were 0, 50, 150, and 450 mg/kg/day for 10 rats/sex/dose and 0, 35, 70, and 140 mg/kg/day for 4 dogs/sex/dose. Three rats at the high dose, 2 males and 1 female, died prior to scheduled sacrifice. Reduced weight gain, decreased activity, tremors, hunched posture, and poor grooming were seen in high dose survivors. Increased alanine aminotransferase (ALT) and aspartate aminotransferase (AST) activities at the mid and high doses suggested hepatotoxicity, although liver weights and histology were normal. Hematology parameters were unaffected except for slight, dose-related increases of platelets in both sexes. Injection site inflammation was seen; however, serum creatine kinase activity was not altered. In dogs, slight weight loss, vomiting, salivation, and diarrhea occurred at the high dose, but no deaths were observed at any of the doses. As with rats, dose-related increases in ALT and AST activities occurred at the mid and high doses, and were, in this case, accompanied at the high dose by hepatomegaly and hepatocellular vacuolization. Cardiotoxicity was evidenced by increased relative heart weights and subtle ECG changes, the latter of which occurred almost exclusively at the highest dose. Injection site inflammation, which was accompanied by dose-related elevations in serum CK-MM2 activity, was also observed.

Repeated-Dose and Subchronic Toxicity Studies of 2,2,2-Trichloroethanol in Sprague-Dawley Rats

1991 ◽  
Vol 10 (2) ◽  
pp. 223-232
Author(s):  
J. Peter Bercz ◽  
Merrel Robinson ◽  
Lucille M. Garner ◽  
Norbert P. Page ◽  
Greg R. Olson
Keyword(s):  
Toxic Effect ◽  
Clinical Symptoms ◽  
Clinical Chemistry ◽  
Lactic Dehydrogenase ◽  
Target Organ ◽  
Male Rats ◽  
High Dose ◽  
Sprague Dawley ◽  
Sprague Dawley Rats ◽  
Dose Levels

Male and female Sprague-Dawley rats were administered 2,2,2-trichloroethanol (TCE) by gavage for 14 or 90 consecutive days. The gavage solution consisted of TCE dissolved in distilled water, containing 10% Emulphor. Doses of 37.5, 75, 150, and 300 mg/kg/day in the 14-day study and 40, 80, 160, and 320 mg/kg/day for the 90-day study were employed. Evaluation of clinical symptoms, clinical chemistry, and pathology examinations did not reveal a specific toxic effect or identify a target organ. In male rats an increase of red blood cells (RBCs) and hematocrit (Hct) in both 14- and 90-day studies, as well as increased hemoglobin (Hgb) in the 90-day study was observed at the highest dose level. In the high-dose females only increase of Hgb was seen in the 14-day study. These hematopoietic indices were not accompanied by commensurate changes in reticulocytes, mean corpuscular volumes or spleen weights. Serum lactic dehydrogenase (LDH) levels were increased in males at the two highest dose levels of both studies. Other changes in chemistries were sporadic in nature and did not appear to be dose related. Collectively, there was no basis to identify a target organ. The RBC and LDH levels did not correlate with other biochemical or pathology results and did not support the hypothesis that they represent a specific toxic effect. Based on the lack of detectable toxicity of TCE at the highest doses tested in rats, the following lowest observed adverse effect levels (LOAEL) were assigned for this chemical: in the 14-day exposure, 300 mg/kg/day for both sexes; in the 90-day protocol, 320 mg/kg/day for female; and 160 mg/kg/day for male rats.

Effects of uranium depletion on 1α-hydroxylase in kidney of rats

2010 ◽  
Vol 30 (7) ◽  
pp. 786-790 ◽  
Author(s):  
Minfen Yan ◽  
Gaoren Zhong ◽  
Linfeng Gao ◽  
Xiqiao Xia ◽  
Lihua Wang ◽  
...  
Keyword(s):  
Active Form ◽  
Underlying Mechanism ◽  
Biologically Active ◽  
Control Group ◽  
High Dose ◽  
Sprague Dawley ◽  
Blank Control Group ◽  
Sprague Dawley Rats ◽  
Dose Levels ◽  
Medium Dose

This study was designed to evaluate the effects of depleted uranium (DU) on 1α-hydroxylase in the kidney of rats and to delinerate the mechanism of damage to kidneys and bones by DU. Male Sprague-Dawley rats were surgically implanted with DU fragments at three dose levels (0.1 g, 0.2 g and 0.3 g). After 3, 6 or 12 months, the concentration of 1α,25(OH)2D3 in the kidney was measured by radioimmunoassay. The activity of 1α-hydroxylase was shown by the production of 1α,25(OH)2D3 after incubation. The results showed that the 1α-hydroxylase activity in the kidney was decreased after 3 months (27.2% at the medium dose DU group, p < 0.05; 33.4% at the high dose DU group, p < 0.01). In contrast, at 6 months and 12 months after implantation of DU, the activity of renal 1α-hydroxylase in DU-treated animals was not decreased significantly in comparison with the controls (p > 0.05). On the other hand, the activity of renal 1α-hydroxylase was decreased by 33.1% (p < 0.05) and 34.4% (p < 0.01) in blank control groups at 6 and 12 months, respectively, when compared with the blank control group at 3 months. In conclusion, this study showed that chronic DU exposure could induce renal damages and inhibit the synthesis of biologically active form of vitamin D, which may be the underlying mechanism of bone metabolic disorder caused by renal injury after DU exposure.

Fourteen-and Ninety-Day Oral Toxicity Studies of Methyl Tertiary-Butyl Ether in Sprague-Dawley Rats

1990 ◽  
Vol 9 (5) ◽  
pp. 525-540 ◽  
Author(s):  
M. Robinson ◽  
R.H. Bruner ◽  
G.R. Olson
Keyword(s):  
Body Weight ◽  
Corn Oil ◽  
Uneventful Recovery ◽  
Methyl Tertiary Butyl Ether ◽  
High Dose ◽  
Sprague Dawley ◽  
Butyl Ether ◽  
Tertiary Butyl ◽  
Sprague Dawley Rats ◽  
Dose Levels

Male and female Sprague-Dawley rats were gavaged with methyl tertiary-butyl ether (MtBE) for 14 or 90 days to evaluate subacute and subchronic toxicity. Five daily dose levels ranged from 0 to 1428 mg/kg body weight for the 14 day study and 0 to 1200 mg/kg body weight for the 90-day exposure. Controls received the corn oil vehicle. At or above dose levels of 1200 mg/kg, MtBE-induced anesthesia lasted about 2 h, followed by uneventful recovery. Diarrhea was common in all treatment groups, but no deaths were attributed to MtBE toxicity. In the subacute study, lung weights were reduced in high-dose females. Trends in the 14-day exposure also included increased cholesterol in both females and males and decreased blood-urea nitrogen (BUN) and creatinine in females. In the 90-day study, females exhibited elevated cholesterol and decreased BUN, while creatinine was decreased in high-dose males. Microscopic findings in most organs were unremarkable, except for high-dose males where renal changes were compatible with alpha 2-globulin nephropathy and were considered to have little toxicologic significance for humans. Both studies indicated that dose levels below those which induce anesthesia (1200 mg/kg) do not result in significant pathophysiologic changes.

scholarly journals Reduction of the sevoflurane minimum alveolar concentration induced by methadone, tramadol, butorphanol and morphine in rats

2012 ◽  
Vol 46 (3) ◽  
pp. 200-206 ◽  
Author(s):  
Mariana Abreu ◽  
Delia Aguado ◽  
Javier Benito ◽  
Ignacio A Gómez de Segura
Keyword(s):  
Minimum Alveolar Concentration ◽  
Intraperitoneal Administration ◽  
Control Group ◽  
High Dose ◽  
Dependent Manner ◽  
Sprague Dawley ◽  
Sprague Dawley Rats ◽  
Before And After ◽  
High Doses ◽  
Dose Dependent

This study aimed to estimate the reduction in the minimum alveolar concentration (MAC) of sevoflurane induced by low and high doses of methadone (5 and 10 mg/kg), tramadol (25 and 50 mg/kg), butorphanol (5 and 10 mg/kg) or morphine (5 and 10 mg/kg) in the rat. A control group received normal saline. Sixty-three adult male Sprague-Dawley rats were anaesthetized with sevoflurane ( n = 7 per group). Sevoflurane MAC was then determined before and after intraperitoneal administration of the opioids or saline. The duration of the sevoflurane MAC reduction and basic cardiovascular and respiratory measurements were also recorded. The baseline MAC was 2.5 (0.3) vol%. Methadone, tramadol and morphine reduced the sevoflurane MAC (low dose: 31 ± 10, 38 ± 15 and 30 ± 13% respectively; high dose: 100 ± 0, 83 ± 17 and 77 ± 25%, respectively) in a dose-dependent manner. The low and high doses of butorphanol reduced the sevoflurane MAC to a similar extent (33 ± 7 and 31 ± 4%, low and high doses, respectively). Two rats developed apnoea following administration of high-dose butorphanol and methadone. These anaesthetic-sparing effects are clinically relevant and may reduce the adverse effects associated with higher doses of inhalational anaesthetics.

Intraneuronal accumulations of lysosomes in the cerebellum of rats and dogs after dosing with MDL-832

1990 ◽  
Vol 48 (3) ◽  
pp. 830-831
Author(s):  
S.D. Barnard ◽  
S.D. Warner
Keyword(s):  
Brown Pigment ◽  
Beagle Dogs ◽  
Sprague Dawley ◽  
Gelatin Capsules ◽  
Pigment Granules ◽  
Sprague Dawley Rats ◽  
Hematoxylin And Eosin ◽  
Dose Levels

1, 2, 9, 10-tetramethoxyaporphine phosphate (MDL-832) was once considered a potential human antitussive. MDL-832 was administered orally in the diets of Sprague-Dawley rats at dose levels of 0, 5, 10, 20, 40, 80 and 160 mg/kg/day for 3 and 6 months and in gelatin capsules to Beagle dogs at 0, 5, 10, 15, 30 and 60 mg/kg/day for 3, 6 and 12 months. Histopathologic examinations of hematoxylin and eosin-stained cerebellar sections revealed intracytoplasmic brown pigment accumulations in large fusiform neurons (presumably the motor type) of the pons. The pigment granules were found to be PAS-positive, non-acid fast, iron-free, Sudan B-positive and fuchsinophilic. Intraneuronal pigment accumulations were seen in rats after 3 months of treatment at 80 mg but not at 40 mg and after 6 months at 20 mg but not at 10 mg. For dogs the effect was observed after 3 months at 60 mg but not at 30 mg and after 12 months at 10 mg but not at 5 mg.

scholarly journals Antidepressant-Like Effect of Lipid Extract ofChanna striatusin Postpartum Model of Depression in Rats

2017 ◽  
Vol 2017 ◽  
pp. 1-15 ◽  
Author(s):  
Mohamed Saleem Abdul Shukkoor ◽  
Mohamad Taufik Hidayat Bin Baharuldin ◽  
Abdul Manan Mat Jais ◽  
Mohamad Aris Mohamad Moklas ◽  
Sharida Fakurazi ◽  
...  
Keyword(s):  
Postpartum Period ◽  
Estradiol Benzoate ◽  
Plasma Corticosterone ◽  
Positive Control ◽  
Lipid Extract ◽  
High Dose ◽  
Sprague Dawley ◽  
Sprague Dawley Rats ◽  
Malay Population ◽  
Swimming Test

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.

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.

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

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.

scholarly journals Toxicity associated with ingestion of a polyacrylic acid hydrogel dog pad

2018 ◽  
Vol 30 (5) ◽  
pp. 708-714 ◽  
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.

Androgen-mediated sex differences of cardiovascular responses in rats

1978 ◽  
Vol 235 (2) ◽  
pp. H242-H246 ◽  
Author(s):  
P. J. Baker ◽  
E. R. Ramey ◽  
P. W. Ramwell
Keyword(s):  
Sex Differences ◽  
Arachidonic Acid ◽  
Rank Order ◽  
Cardiovascular Responses ◽  
Sprague Dawley ◽  
Similar Treatment ◽  
Depressor Response ◽  
Sprague Dawley Rats ◽  
Significant Change ◽  
Dose Levels

Sex differences in the systemic depressor response to arachidonic acid (50 or 150 microgram/kg iv) were observed in intact and castrated anesthetized Sprague-Dawley rats. The rank order of responsiveness was: castrate males, castrate females, females, males; all four groups were significantly different (P less than 0.05) at the higher dose. Castrated males pretreated with testosterone (1 mg/kg sc) 5 or 7 days previously gave a response at the higher arachidonate dose levels that was of the same order as that obtained with intact males. Similar treatment of castrate males with androgen potentiated (P less than 0.05) the vasopressor action of norepinephrine (0.25 microgram/kg) on day 7 after the testosterone pretreatment. In contrast, treatment with depot estradiol (100 microgram/kg sc) in castrate males produced no significant change in the response to either of the vasoactive compounds on both days 5 and 7 after pretreatment. These data suggest that testosterone may be a significant factor in the development of sex differences in the cardiovascular systems of rats.

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