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.

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.

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.

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.

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.

Plasma metabolite and hormone concentrations in Friesian cows of differing genetic merit measured at two feeding levels

1984 ◽  
Vol 38 (3) ◽  
pp. 377-384 ◽  
Author(s):  
D. S. Flux ◽  
D. D. S. Mackenzie ◽  
G. F. Wilson
Keyword(s):  
Growth Hormone ◽  
Blood Metabolites ◽  
Blood Samples ◽  
Genetic Merit ◽  
The United Kingdom ◽  
Metabolite Concentrations ◽  
Plasma Metabolite ◽  
Milk Solids ◽  
Mean Concentration ◽  
Friesian Cows

ABSTRACTPhysiological differences between cows in hormone and metabolite concentrations were sought that may account for genetic differences in milk production.Two groups of New Zealand Friesian cows, differing in genetic merit for fat production (high breeding index (HBI) and low breeding index (LBI)) by approximately 23 breeding index units (20 kg fat on the United Kingdom improved contemporary comparison scale), were each divided into two further groups, one of which was given freshly cut pasture to appetite and in the other intake was restricted to 70% of appetite. Eighteen blood samples were collected over a 24-h period from each of 16 cows fitted with indwelling jugular catheters. Samples were analysed for growth hormone, insulin, free fatty acids and β-hydroxybutyrate. Mean concentration of insulin was significantly higher in the HBI underfed group than in any other group (P < 0·01). Glucose concentration was significantly lower in the LBI group (P < 0·05), whose intake was restricted. The concentration of (3-hydroxybutyrate was significantly higher in the cows whose intake was restricted (P < 0·01) and the concentration fell markedly after feeding. Growth hormone concentrations were higher in the cows on restricted intake (P < 0·05) and in HBI cows but the differences were not statistically significant.It was concluded that different patterns of blood metabolites and hormones are associated with cows that differ in genetic merit. Aspects of insulin and glucose metabolism, particularly at low planes of feeding, appear to offer most promise as indicators of high milk-solids production.

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.

scholarly journals Vapor inhalation of cannabidiol (CBD) in rats

2019 ◽  
Author(s):  
Mehrak Javadi-Paydar ◽  
Kevin M. Creehan ◽  
Tony M. Kerr ◽  
Michael A. Taffe
Keyword(s):  
Wistar Rats ◽  
Temperature Response ◽  
The Body ◽  
Nociceptive Response ◽  
Preclinical Studies ◽  
Sprague Dawley ◽  
Blood Samples ◽  
Clinical Model ◽  
Sprague Dawley Rats ◽  
Female Wistar Rats

AbstractCannabidiol (CBD) is increasingly available in e-cigarette liquids and other products. CBD use has been promoted for numerous purported benefits which have not been rigorously assessed in preclinical studies. The objective of this study was to further validate an inhalation model to assess CBD effects in the rat. The primary goal was to determine plasma CBD levels after vapor inhalation and compare that with the levels observed after injection. Secondary goals were to determine if hypothermia is produced in male Sprague-Dawley rats and if CBD affects nociception measured by the warm water tail-withdrawal assay. Blood samples were collected from rats exposed for 30 minutes to vapor generated by an e-cigarette device using CBD (100, 400 mg/mL in the propylene glycol vehicle). Separate experiments assessed the body temperature response to CBD in combination with nicotine (30 mg/mL) and the anti-nociceptive response to CBD. Vapor inhalation of CBD produced concentration-related plasma CBD levels in male and female Wistar rats that were within the range of levels produced by 10 or 30 mg/kg, CBD, i.p.. Dose-related hypothermia was produced by CBD in male Sprague-Dawley rats and this was partially attenuated by 5-HT1a receptor blockade. Nicotine (30 mg/mL) inhalation enhanced the effect of CBD. CBD inhalation had no effect on anti-nociception alone or in combination with Δ9-tetrahydrocannabinol inhalation. The vapor-inhalation approach is a suitable pre-clinical model for the investigation of the effects of inhaled CBD. This route of administration produces hypothermia in rats, while i.p. injection does not at comparable plasma CBD levels.

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