Plasma Cocaine Metabolite Levels and Liver CYP450 3A4 Isoenzyme Activity as Indicators of Cocaine Metabolism in Rats Treated With Salako Supplements

2019 ◽  
pp. 1-21
Author(s):  
Natwaine Sherune Gardner ◽  
Kedon J. S. Luke ◽  
Andrew O. Wheatley ◽  
Winston De La Haye ◽  
Perceval Steven Bahado-Singh ◽  
...  
Keyword(s):  
Plasma Clearance ◽  
Liver Homogenate ◽  
Nutritional Supplements ◽  
Test Results ◽  
Sprague Dawley ◽  
Blood Samples ◽  
Sprague Dawley Rats ◽  
Chronic Cocaine ◽  
One Way Anova ◽  
Range Test

The effects of Salako nutritional supplements on cocaine-dependent Sprague Dawley rats was investigated. Rats were made cocaine-dependent using conditioned place preference (CPP) where craving was analyzed regularly. Cocaine metabolite levels were determined from blood samples. CYP450 3A4 isoenzyme activities were obtained using liver homogenate. Statistical analysis was done using SPSS one-way ANOVA and Duncans multiple range test. Results show that when cocaine use was discontinued, the supplements reduced craving of cocaine significantly. Blood plasma results showed higher benzoylecgonine equilibrium possibly indicating that the supplements aided the removal of stored cocaine metabolites which may have contributed to better management of craving in the rats. CYP450 3A4 isoenzyme activity was further enhanced by the supplements and is indicative of increased cocaine metabolism. The results indicate that the Salako nutritional supplements reduce craving caused by chronic cocaine administration by increasing the liver CYP450 3A4 isoenzyme activity, resulting in better plasma clearance.

Plasma Cocaine Metabolite and Liver CYP450 3A4 Isoenzyme Levels as Indicators of Cocaine Dependence in Rats Treated with Nutritional Supplements

2015 ◽  
Vol 5 (2) ◽  
pp. 28-43 ◽  
Author(s):  
Natwaine Sherune Gardner ◽  
Kedon JS Luke ◽  
Andrew O. Wheatley ◽  
Winston G. De La Haye ◽  
Perceval Bahado-Singh ◽  
...  
Keyword(s):  
Plasma Clearance ◽  
Nutritional Supplements ◽  
Cytochrome P450 3A4 ◽  
Sprague Dawley ◽  
Plasma Analysis ◽  
Blood Samples ◽  
Sprague Dawley Rats ◽  
Chronic Cocaine ◽  
Metabolite Concentrations ◽  
Plasma Metabolite

The effects that chronic cocaine administration (CCA) have on craving, cocaine metabolite concentrations and cytochrome P450 3A4 isoenzyme (CYP450 3A4) activities in Sprague-Dawley rats following the administration of Salako Nutritional Supplements (SNS) were examined. Five groups of fifty rats were used to assess the effect of the SNS following CCA. Craving was analyzed for each rat using a Conditioned Place Preference protocol. Blood samples were obtained at regular intervals and used to measure cocaine plasma metabolite levels. CYP450 3A4 activity was determined in the liver. Administration of the SNS reduced craving of cocaine significantly, upon discontinuing cocaine in the rats. Blood plasma analysis showing higher benzoylecgonine equilibrium and the CYP450 3A4 levels demonstrated that the SNS possibly aided in the removal of the stored metabolites indicative of increased metabolism of cocaine, enhanced by the Supplements. Results indicate that the SNS formulation reduces craving caused by CCA by increasing the liver CYP450 3A4 activity, resulting in better plasma clearance.

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.

Toxicologic Evaluation of Cellulon™ Fiber; Genotoxicity, Pyrogenicity, Acute and Subchronic Toxicity

1991 ◽  
Vol 10 (5) ◽  
pp. 541-554 ◽  
Author(s):  
Donald F. Schmitt ◽  
Vasilios H. Frankos ◽  
John Westland ◽  
Tracey Zoetis
Keyword(s):  
Microcrystalline Cellulose ◽  
Test Material ◽  
Test Results ◽  
Sprague Dawley ◽  
Subchronic Toxicity ◽  
Genotoxic Potential ◽  
Dermal Irritation ◽  
Sprague Dawley Rats ◽  
Activation Assay ◽  
Mutation Assay

CellulonTM fiber, a cellulose produced by a bacterial fermentation process employing a strain of Acetobacter aceti subsp. xylinum, was tested for genotoxicity in four assays: (1) microbial reverse mutation assay in Salmonella typhimurium (Ames assay), (2) an assay for chromosomal aberrations in Chinese hamster ovary (CHO) cells, (3) an assay for induction of unscheduled DNA synthesis (UDS) in rat primary hepatocytes, and (4) the CHO/HGPRT forward mutation assay. Each assay was conducted at a wide range of dose levels, both with and without metabolic activation (assay 1, 2, and 4). Test results gave no indication that Cellulon fiber possessed any genotoxic potential. The pyrogenicity of five batches of Cellulon fiber was tested in the Limulus Amebocyte Lysate assay, gel-clot method. Test results were negative for the presence of gram-negative bacterial endotoxin. The primary eye and dermal irritation potential of Cellulon fiber were examined in New Zealand White rabbits. The Draize method was employed to evaluate and grade ocular and dermal irritation as a result of test material administration. Test results indicated that Cellulon fiber is a minor ocular irritant up to 1 hour postadministration. However, the resultant irritation was considered to be mechanical and related to the dry, granular form of the test material. In addition, test results indicated that Cellulon fiber is not a dermal irritant in the rabbit. The acute oral toxicity of Cellulon fiber was determined in Sprague-Dawley rats, and the LD50 was found to be greater than 2000 mg/kg of body weight. The subchronic toxicity of Cellulon fiber was examined in Sprague-Dawley rats fed diets containing 0, 5, and 10% Cellulon fiber or microcrystalline cellulose for 13 weeks. No dose-related effects on survival, growth, hematology, blood chemistry, organ weights, or pathologic lesions were observed. The results of these studies indicate that Cellulon fiber and microcrystalline cellulose are toxicologically equivalent and that Cellulon fiber does not possess genotoxic potential, is nonpyrogenic, and that animals are not adversely affected by acute or subchronic exposure to Cellulon fiber.

Pharmacokinetics of All-trans Retinoyl beta-Glucuronide in Rats following Intraperitoneal and Oral Administration

2003 ◽  
Vol 73 (4) ◽  
pp. 251-257 ◽  
Author(s):  
Romans ◽  
Barua ◽  
Olson
Keyword(s):  
High Performance Liquid Chromatography ◽  
Single Dose ◽  
High Performance ◽  
Corn Oil ◽  
Major Product ◽  
Plasma Samples ◽  
Sprague Dawley ◽  
Blood Samples ◽  
Sprague Dawley Rats ◽  
Plasma Retinol

The purpose of this study was to examine the pharmacokinetics of a single dose (6.3 mumol, 3 mg) of all-trans retinoyl beta-glucuronide (RAG), when given either orally in corn oil or by intraperitoneal (IP) injection in dimethylsulfoxide (DMSO) to adult Sprague-Dawley rats. Following dosing, serial blood samples were collected at various times up to 48 hours from each rat via saphenous vein puncture. Retinoids were extracted from plasma samples and analyzed by high-performance liquid chromatography. In the plasma of IP-dosed rats (n = 6), a derivative of RAG, tentatively identified as the lactone of RAG (RAGL), was the major product found. RAGL persisted in the plasma for up to 48 hours. Much smaller concentrations of RAG and of retinoic acid (RA) were also present in the plasma at two to four hours, but generally not thereafter. In orally dosed rats (n = 6), neither RAG nor its products, except for occasional traces of the lactone, were detected. Plasma retinol levels decreased in both IP-injected and orally treated rats, the decrease being significant in orally dosed rats.

scholarly journals PROTECTIVE EFFECT OF KADUKKAI MAATHIRAI (TERMINALIA CHEBULA-BASED POLYHERBAL SIDDHA FORMULATION) IN ETHANOL-INDUCED LIVER DISEASE IN RATS

2018 ◽  
Vol 11 (11) ◽  
pp. 368
Author(s):  
Manjunath Shetty ◽  
Smita Shenoy ◽  
Vasudha Devi ◽  
Nitesh Kumar ◽  
Arul Amuthan ◽  
...  
Keyword(s):  
Liver Enzymes ◽  
Liver Parenchyma ◽  
Treated Group ◽  
Therapeutic Dosage ◽  
Sprague Dawley ◽  
Gum Acacia ◽  
Sprague Dawley Rats ◽  
Post Hoc ◽  
One Way Anova ◽  
Normal Architecture

Objective: The objective of this study was to evaluate the prophylactic effect of Kadukkai maathirai (KM) against ethanol-induced hepatotoxicity in rats.Methods: Four groups (n=6) of adult female Sprague–Dawley rats were used. Ethanol was administered in the dose of 45% v/v 15 mL/kg/body weight twice a day for 8 weeks in the study. The four groups were treated orally for 8 weeks with 2% gum acacia (control), ethanol (toxic control), ethanol + KM 72 mg/kg, and ethanol + KM 400 mg/kg, respectively. At the end of 8 weeks, blood was collected by a retro-orbital puncture for the estimation of liver enzymes (aspartate aminotransferase [AST] and alanine aminotransferase [ALT]). The liver was dissected out for histopathology. Using one-way ANOVA and post hoc Tukey’s test, the data were analyzed.Results: There was a significant (p<0.05) decrease in the serum AST and ALT level in rats treated with KM 72 mg/kg as compared to toxic control. Liver parenchyma showed near normal architecture in KM 72 mg/kg-treated group as compared to ethanol-treated group which showed extensive ballooning degeneration of hepatocytes and microvesicular steatosis.Conclusion: KM, in the dose of 72 mg/kg, which is the therapeutic dosage described in Siddha additional literature, exerted hepatoprotective effect against ethanol-induced liver damage in rats.

The effect of thyroid dysfunction on nesfatin-1 and adiponectin levels in rats

2017 ◽  
Vol 32 (3) ◽  
Author(s):  
Emine Atıci ◽  
Rasim Mogulkoc ◽  
Abdulkerim Kasım Baltaci ◽  
Esma Menevse
Keyword(s):  
Body Weight ◽  
Thyroid Hormone ◽  
Thyroid Dysfunction ◽  
The Other ◽  
High Dose ◽  
Fat Cells ◽  
Sprague Dawley ◽  
Blood Samples ◽  
Sprague Dawley Rats ◽  
Experimental Thyroid

AbstractBackgroundChanges in thyroid hormone concentrations may affect adiponectin concentrations through various mechanisms. A molecule released primarily from the fat cells adiposities; adiponectin has important effects on the regulation of body weight.AimThe present study aimed to explore the effects of experimental thyroid dysfunction and its treatment on nesfatin-1 and adiponectin levels in rats.MethodsThe study included 40 adult male Sprague-Dawley rats which were grouped as follows: (1) control; (2) hypothyroidism [hypothyroidism was induced by intraperitoneal injection of 10 mg/kg/day propylthiouracil (PTU) for 3 weeks]; (3) hypothyroidism + thyroxine group [after hypothyroidism was induced by 2-week PTU injection, they were treated with high-dose L-thyroxine (1.5 mg/kg/day) for 1 week]; (4) hyperthyroidism [hyperthyroidism was induced by 3-weeks’ thyroxine injection (0.3 mg/kg/day)]; (5) hyperthyroidism + PTU (after hyperthyroidism was induced by 2-weeks’ thyroxine injection, the animals were given 10 mg/kg/day PTU for 1 week). Blood samples taken at the end of the study were analyzed to measure nesfatin-1 and adiponectin levels.ResultsIt was found that nesfatin-1 levels increased in hypothyroidism, while adiponectin levels decreased (p < 0.001). In experimental hyperthyroidism, on the other hand, both nesfatin-1 and adiponectin levels were found significantly elevated (p < 0.001).ConclusionThe results of the study indicate that nesfatin-1 and adiponectin levels were modified considerably in hypo- and hyperthyroidism, whereas with the restoration of the thyroid function, modified hormone levels went back to normal.

Pharmacokinetic Profile of Curcumin and Nanocurcumin in Plasma, Ovary, and Other Tissues

Drug Research ◽  
2019 ◽  
Vol 69 (10) ◽  
pp. 559-564 ◽  
Author(s):  
Wawaimuli Arozal ◽  
Wenny Trias Ramadanty ◽  
Melva Louisa ◽  
Regina Puspa Utami Satyana ◽  
Gaviota Hartono ◽  
...  
Keyword(s):  
Ovarian Cancer ◽  
Particle Size ◽  
Pharmacokinetic Profile ◽  
Pharmacokinetic Parameters ◽  
Absorption Process ◽  
Sprague Dawley ◽  
Particle Size Reduction ◽  
Blood Samples ◽  
Sprague Dawley Rats ◽  
Low Solubility

Abstract Background Curcumin is a natural diphenolic compound that is currently being investigated for various cancers, including ovarian cancer. Clinical application of curcumin has been limited due to its low solubility and bioavailability and rapid metabolism and degradation at physiological pH. Particle size is one factor that can affect the absorption process, which thus increases compound solubility and transport across the membrane. This study was conducted to determine the effects of modifying the particle size of curcumin on its pharmacokinetic parameters in blood and other organs. Methods Female Sprague Dawley rats were administered a single oral dose of 500 mg/kg curcumin or nanocurcumin. Blood samples were collected at 10, 15, 30, 45, 75, and 120 min, and ovaries, livers, kidneys, and colons were collected at 180 min. The levels of curcumin in plasma and organs were determined using UPLC-MS/MS, and the pharmacokinetic parameters were evaluated. Results Curcumin levels were detectable and measurable in plasma and organs of rats that were administered curcumin or nanocurcumin. Overall, no statistically significant differences were found in pharmacokinetic parameters between curcumin and nanocurcumin groups in both plasma and organs, except for ovaries. The curcumin levels in plasma, liver, kidney, and colon in the curcumin group were higher than those in the nanocurcumin group. However, curcumin concentrations in ovaries in the nanocurcumin group were 3.6 times higher than those in the curcumin group. Conclusion Particle size reduction of curcumin did not increase the concentration of curcumin in the plasma but increased its distribution in the ovaries.

Both hypothyroidism and hyperthyroidism increase plasma irisin levels in rats

2017 ◽  
Vol 33 (3) ◽  
Author(s):  
Emine Atici ◽  
Rasim Mogulkoc ◽  
Abdulkerim Kasim Baltaci ◽  
Esma Menevse
Keyword(s):  
Body Weight ◽  
Adult Male ◽  
Thyroid Dysfunction ◽  
The Other ◽  
Sprague Dawley ◽  
Free Triiodothyronine ◽  
Blood Samples ◽  
Other Hand ◽  
Sprague Dawley Rats ◽  
Experimental Thyroid

AbstractBackgroundA recently discovered hormone, irisin is accepted to be significantly involved in the regulation of body weight. Thyroid functions may be, directly or indirectly, associated with irisin.AimThe aim of the present study is to determine the effect of experimental thyroid dysfunction on irisin levels in rats.MethodsThe study registered 40 adult male Sprague-Dawley rats, which were allocated to groups as follows: 1. Control; 2. Hypothyroidism induced by injection of 10 mg/kg/day intraperitoneal propylthiouracil (PTU) for 3 weeks; 3. Hypothyroidism (PTU 2 weeks) + L-thyroxin (1.5 mg/kg/day for 1 week); 4. Hyperthyroidism induced in rats by 3-week thyroxin (0.3 mg/kg/day); 5. Hyperthyroidism + PTU. At the end of the study, blood samples were collected to quantify free triiodothyronine (FT3), free triiodothyronine (FT4) and irisin levels.ResultsFT3and FT4levels were reduced in hypothyroidism and were significantly elevated in hyperthyroidism (p < 0.001). Irisin values, on the other hand, were found to be elevated in both hypothyroidism and hyperthyroidism groups (p < 0.001).ConclusionThe results of the study suggest that irisin values increase in thyroid dysfunction, hypo- and hyperthyroidism, and that when hypothyroidism is corrected by thyroxin administration and hyperthyroidism by PTU injection, plasma irisin values go back to normal.

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