Respiratory safety pharmacology: Positive control drug responses in Sprague–Dawley rats, Beagle dogs and cynomolgus monkeys

2009 ◽  
Vol 55 (2) ◽  
pp. 229-235 ◽  
Author(s):  
Simon Authier ◽  
Margarita Legaspi ◽  
Dominique Gauvin ◽  
Eric Troncy
Keyword(s):  
Positive Control ◽  
Beagle Dogs ◽  
Sprague Dawley ◽  
Drug Responses ◽  
Cynomolgus Monkeys ◽  
Safety Pharmacology ◽  
Control Drug ◽  
Sprague Dawley Rats

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.

Ranitidine as an alcohol dehydrogenase inhibitor in acute methanol toxicity in rats

2009 ◽  
Vol 29 (2) ◽  
pp. 93-101 ◽  
Author(s):  
Amal A El-Bakary ◽  
Sahar A El-Dakrory ◽  
Sohayla M Attalla ◽  
Nawal A Hasanein ◽  
Hala A Malek
Keyword(s):  
Alcohol Dehydrogenase ◽  
High Performance ◽  
Negative Control Group ◽  
Positive Control ◽  
Negative Control ◽  
Control Group ◽  
Sprague Dawley ◽  
Blood Samples ◽  
Methanol Poisoning ◽  
Sprague Dawley Rats

Methanol poisoning is a hazardous intoxication characterized by visual impairment and formic acidemia. The therapy for methanol poisoning is alcohol dehydrogenase (ADH) inhibitors to prevent formate accumulation. Ranitidine has been considered to be an inhibitor of both gastric alcohol and hepatic aldehyde dehydrogenase enzymes. This study aimed at testing ranitidine as an antidote for methanol acute toxicity and comparing it with ethanol and 4-methyl pyrazole (4-MP). This study was conducted on 48 Sprague-Dawley rats, divided into 6 groups, with 8 rats in each group (one negative control group [C1], two positive control groups [C2, C3] and three test groups [1, 2 and 3]). C2, C3 and all test groups were exposed to nitrous oxide by inhalation, then, C3 group was given methanol (3 g/kg orally). The three test groups 1, 2 and 3 were given ethanol (0.5 g/kg orally), 4-MP (15 mg/kg intraperitoneally) and ranitidine (30 mg/kg intraperitoneally), respectively, 4 hours after giving methanol. Rats were sacrificed and heparinized, cardiac blood samples were collected for blood pH and bicarbonate. Non-heparinized blood samples were collected for formate levels by high performance liquid chromatography. Eye balls were enucleated for histological examination of the retina. Ranitidine corrected metabolic acidosis (p = .025), decreased formate levels (p = .014) and improved the histological findings in the retina induced by acute methanol toxicity.

scholarly journals PENGARUH SINBIOTIK KEFIR PISANG BATU TERHADAP KADAR KOLESTEROL-LDL DAN KOLESTEROL-HDL TIKUS MODEL SINDROM METABOLIK

2020 ◽  
Vol 7 (2) ◽  
pp. 280-288
Author(s):  
Dina Khoiriyah ◽  
Taufik Maryusman ◽  
Santi Herlina
Keyword(s):  
Risk Factors ◽  
Metabolic Syndrome ◽  
Ldl Cholesterol ◽  
Hdl Cholesterol ◽  
Positive Control ◽  
Negative Control ◽  
Sprague Dawley ◽  
Musa Balbisiana ◽  
Cholesterol Levels ◽  
Sprague Dawley Rats

Effect of Banana Kefir Synbiotic on LDL-Cholesterol and HDL-Cholesterol of Metabolic Syndrome Rats Metabolic syndrome (SM) is characterized by several risk factors including dyslipidemia. This study aims to analyze the effect of kefir synbiotic produced from banana stone flour (Musa balbisiana) on LDL-cholesterol and HDL-cholesterol of metabolic syndrome rat model. The 24 Sprague Dawley rats were divided into four groups, namely negative control (healthy rats fed standard feed), positive control (metabolic syndrome rats fed standard feed), treatment I and treatment II (metabolic syndrome rats each given synbiotic kefir banana stone flour 1.8 mL/200 g mouse BW/day and 3.6 mL/200 g mouse BW/day, respectively). The intervention was carried out for three weeks. After the intervention, the levels of LDL-cholesterol in treatment I and II experienced a decrease of 44.66% and 56.94%, respectively, while the-HDL-cholesterol levels in treatment I and II experienced an increase of 104.5% and 172.71%, respectively. The biggest change occurred in treatment II. Synbiotic kefir banana stone flour improved lipid profile in metabolic syndrome rats. Sindrom metabolik (SM) ditandai dengan beberapa faktor risiko termasuk dislipidemia. Penelitian ini bertujuan untuk menganalisis pengaruh sinbiotik kefir tepung pisang batu (Musa balbisiana) terhadap kadar kolesterol-LDL dan kolesterol-HDL tikus model SM. Subjek menggunakan 24 ekor tikus Sprague Dawley yang dibagi menjadi empat kelompok, yaitu kontrol negatif (tikus sehat yang diberi pakan standar), kontrol positif (tikus model SM yang diberi pakan standar), perlakuan I dan perlakuan II (tikus model SM yang masing-masing diberi sinbiotik kefir tepung pisang batu 1,8 mL/200 g BB tikus/hari dan 3,6 mL/200 g BB tikus/hari). Proses intervensi dilakukan selama tiga minggu. Setelah intervensi, kadar kolesterol-LDL perlakuan I dan II mengalami penurunan sebesar 44,66% dan 56,94%, sedangkan kadar kolesterol-HDL perlakuan I dan II mengalami peningkatan sebesar 104,5% dan 172,71%. Perubahan terbesar terjadi pada perlakuan II. Sinbiotik kefir tepung pisang batu memperbaiki profil lipid tikus sindrom metabolik.

Buprenorphine alleviation of pain does not compromise the rat monoarthritic pain model

2017 ◽  
Vol 16 (1) ◽  
pp. 167-167
Author(s):  
M.S. Berke ◽  
Klas S.P. Abelson
Keyword(s):  
Rat Model ◽  
Joint Stiffness ◽  
Positive Control ◽  
Negative Control ◽  
Pain Tolerance ◽  
Control Group ◽  
Mechanical Stimuli ◽  
Sprague Dawley ◽  
Sprague Dawley Rats ◽  
A Minor

Abstract Aims This study investigated the effects of buprenorphine treatment on pain and welfare parameters and model specific parameters in a rat model of monoarthritis to eliminate unnecessary pain from this model. Methods 32 male Sprague Dawley rats were divided into four groups: (1) A negative control without arthritis receiving no analgesia. (2) A positive monoarthritic control group receiving no analgesia, but subcutaneous saline injections twice a day. (3) A positive control with monoarthritis receiving subcutaneous carprofen once a day and saline once a day. (4) A group with monoarthritis receiving subcutaneous buprenorphine twice a day. Monoarthritis was induced with an injection of 0.02 ml Complete Freund’s Adjuvant intra-articularly in the left tibiotarsal joint. Treatment with analgesia was initiated at day 15 and the rats were euthanized at day 23. Results The induced monoarthritis elicited a pronounced acute inflammation. Several parameters such as bodyweight, mobility, stance, joint-stiffness and lameness scores were affected. A marked mechanical hyperalgesia in the tarsal area was observed by Electronic Von Frey testing, but no severe compromise of the animal welfare was seen at any time. Signs of chronic development began to appear from day 10 after the monoarthritic induction. No significant change in serum cytokines and faecal corticosterone measurements was found after administration of buprenorphine. A minor decrease in body weight was seen, and a higher pain tolerance to mechanical stimuli was observed, indicating pain alleviation. The histological examination confirmed monoarthritic development in all monoarthritic rats and revealed periarticular lesions suggesting diffusion of adjuvant from intra-articular injection site to the periphery. Conclusions The study demonstrated that buprenorphine has an analgesic effect in the adjuvant induced monoarthritic rat model, without obvious interference with the development of arthritis.

Acylcarnitines: drug absorption-enhancing agents in the gastrointestinal tract

1986 ◽  
Vol 251 (3) ◽  
pp. G332-G340 ◽  
Author(s):  
J. A. Fix ◽  
K. Engle ◽  
P. A. Porter ◽  
P. S. Leppert ◽  
S. J. Selk ◽  
...  
Keyword(s):  
Gastrointestinal Tract ◽  
Drug Absorption ◽  
Structural Integrity ◽  
Somatostatin Analogue ◽  
Beagle Dogs ◽  
Sprague Dawley ◽  
Solid Dosage Forms ◽  
Intestinal Tissue ◽  
Solid Dosage ◽  
Sprague Dawley Rats

Acylcarnitines were tested as potential absorption-enhancing agents for drugs that are poorly absorbed from the gastrointestinal tract. Urethan-anesthetized Sprague-Dawley rats and conscious Beagle dogs were used. Palmitoyl-DL-carnitine was the most effective acylcarnitine tested, although significant increases in drug absorption were observed with acylcarnitines containing C12 through C18 fatty acid chains. Palmitoyl-DL-carnitine afforded significant increases in the absorption of cefoxitin, gentamicin, cytarabine, somatostatin analogue, and alpha-methyldopa. The response to palmitoyl-DL-carnitine was concentration dependent and reversible within 60-120 min. Histological examination of the intestinal tissue revealed no apparent change in mucosal structural integrity at doses of palmitoyl-DL-carnitine that resulted in increased drug absorption. The acylcarnitines were effective in increasing drug absorption from the small intestine and the rectal compartment of both rats and dogs. The data also demonstrated effectiveness with aqueous and solid dosage forms (Witepsol H-15 suppositories). The data suggest that acylcarnitines may be effective and safe absorption-enhancing agents for a variety of drugs.

BIOTRANSFORMATION OF A GABAA RECEPTOR PARTIAL AGONIST IN SPRAGUE-DAWLEY RATS AND CYNOMOLGUS MONKEYS: IDENTIFICATION OF TWO UNIQUE N-CARBAMOYL METABOLITES

2005 ◽  
Vol 33 (11) ◽  
pp. 1688-1699 ◽  
Author(s):  
Christopher L. Shaffer ◽  
Mithat Gunduz ◽  
Thomas N. O'Connell ◽  
R. Scott Obach ◽  
Shiyin Yee
Keyword(s):  
Gabaa Receptor ◽  
Partial Agonist ◽  
Sprague Dawley ◽  
Cynomolgus Monkeys ◽  
Sprague Dawley Rats

scholarly journals Anti-osteoporosis effect of Notopterygium incisum Ting ex H. T. Chang extract in rats

2021 ◽  
Vol 18 (10) ◽  
pp. 2051-2055
Author(s):  
Hai Ding ◽  
Wenju Chang ◽  
Jian Yao ◽  
Fendou Liu ◽  
Qingliang Zeng ◽  
...  
Keyword(s):  
Bone Mineral Density ◽  
Bone Mineral ◽  
Serum Alkaline Phosphatase ◽  
Collagen Type I ◽  
Positive Control ◽  
Type I ◽  
Sprague Dawley ◽  
Mineral Density ◽  
Control Drug ◽  
Bone Trabeculae

Purpose: To investigate the effect of Notopterygium incisum Ting ex H.T. Chang extract (NICE) on ovariectomy-induced osteoporosis in rats. Methods: Female Sprague-Dawley rats were randomly assigned to a normal group (control) and five ovariectomy (OVX) subgroups: OVX with vehicle (OVX), OVX with positive control drug alendronate sodium tablets (1.8 mg/kg/week), and OVX with varying NICE doses (45, 90, or 180 mg/kg/day). After rats were subjected to ovariectomy for 4 weeks, alendronate or NICE were administered orally daily for 16 weeks. The bone mineral density (BMD) of the L4 vertebrae and right femurs of all rats was estimated. The serum hormones estradiol (E2), follicle-stimulating hormone (FSH) and luteinizing hormone (LH) levels and serum alkaline phosphatase (ALP), osteocalcin (OC) and telopeptides of collagen type I (CTx) levels of rats were detrmined. Results: The results show that NICE dose-dependently inhibited bone mineral density (BMD) reduction of L4 vertebrae and femurs (p < 0.05). Compared with OVX group, serum E2, FSH and LH levels was significantly increased in osteoporosis rats (p < 0.01), but serum ALP, CTx, and OC concentrations were significantly lower (p < 0.05). On the other hand, bone trabeculae in the three NICE groups and nilestriol group were all wider, while the space and connections increased. Conclusion: These findings indicate that NICE mitigates OVX-induced osteoporosis in rats, and hence can potentially be developed for the management of osteoporosis.

scholarly journals Evaluation of clinical, histology, TNF-α, and collagen expressions on oral ulcer in rats after treatment with areca nut and chrysanthemum oral gel

F1000Research ◽  
2021 ◽  
Vol 10 ◽  
pp. 623
Author(s):  
Liza Meutia Sari ◽  
Zaki Mubarak ◽  
Dina Keumala Sari
Keyword(s):  
Triamcinolone Acetonide ◽  
Positive Control ◽  
Flowering Plant ◽  
Positive Control Group ◽  
Control Group ◽  
Areca Nut ◽  
Sprague Dawley ◽  
Control Groups ◽  
Sprague Dawley Rats ◽  
Tnf Α

Background: Areca nut (Areca catechu Linn.) is the seed of the fruit of the oriental palm that is commonly used among Southeast Asian communities. Chrysanthemum (Dendrathema grandiflora) is a flowering plant originating from East Asia and dominantly grows in China. Both of these plants have strong antioxidant activities. To investigate the mechanism of their wound healing activities, we prepared areca nut and chrysanthemum polyethylene oral gel and performed several in vivo assays using Sprague–Dawley rats. Methods: Sprague–Dawley rats were divided into five groups: Negative control group (rats with base gel treatment), positive control group (rats treated with triamcinolone acetonide), F1 (treatment with 20% areca nut:80% chrysanthemum), F2 (treatment with 50% areca nut:50% chrysanthemum), and F3 (treatment with 80% areca nut:20% chrysanthemum). Traumatic ulcers were performed on the buccal mucosa of all experimental animals that received topical oral gel and triamcinolone acetonide twice a day for seven days. The clinical and histological characteristics were analyzed and scored. Results: During the six days, the ulcerated area receded linearly over time and was completely cicatrized in F2 and positive control group (Dependent t-test, p<0.05). There were significant increases in body weight in F2 and positive control groups. There were no significant differences between groups in histology examination (Kruskal Wallis test, p<0.05). The moderate score of TNF-α levels was seen in F2 and positive control groups (ANOVA/Tukey test). Similar results were seen in the collagenases assay. Conclusions: A balanced combination of areca nut and chrysanthemum extract in the oral gel can optimize the healing of traumatic oral ulcers in rats through the increase of TNF-α and collagen deposition.

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