Tissue distribution and antithrombotic activity of unlabeled or 14C-labeled porcine intestinal mucosal heparin following administration to rats by the oral route

2000 ◽  
Vol 78 (4) ◽  
pp. 307-320 ◽  
Author(s):  
Linda M Hiebert ◽  
Sandra M Wice ◽  
Tilly Ping ◽  
Ronald E Hileman ◽  
Ishan Capila ◽  
...  

Distribution and antithrombotic activity of orally administered unfractionated porcine heparin were studied. [14C]Heparin was prepared by de-N-acetylation of porcine mucosal heparin followed by re-N-acetylation, using [14C]acetic anhydride. [14C]Heparin and (or) cold heparin (60 mg/kg) were administered by stomach tube to male Wistar rats. Blood, all levels of gut and gut contents, liver, lung, spleen, kidney, and aortic and vena caval endothelium were collected under deep anesthesia at 3, 6, 15, 30, and 60 min and 4 and 24 h (6 rats/group) after administration. Urine and feces were collected at 24 h, using metabolic cages. In three additional rats, drugs were administered in gelatin capsules. Tissues listed above and tongue, esophagus, trachea, brain, heart, thymus, bile ducts, vena caval and aortic walls, ureters, bladder, samples of muscle, skin, hair, and bone marrow were collected at 24 h. Radioactivity and chemical heparin, measured by agarose gel electrophoresis, were observed in all tissues examined as well as gut washes, plasma, urine, and feces. Radiolabel recovered was confirmed to be heparin by autoradiograms of gradient polyacrylamide electrophoretic gels. [14C]Heparin and chemical heparin in gut tissue suggest a transit time of 4 h. Porcine or bovine heparin (7.5 mg/kg), administered by stomach tube, decreased the incidence of thrombosis induced by applying 10% formalin in 65% methanol to the exposed jugular vein of rats. Heparin isolation from non-gut tissue, endothelium, urine, and plasma and the observed antithrombotic effect are consistent with oral bioavailability.Key words: heparin, [14C]heparin, oral administration, distribution, radiolabel, thrombosis.

2001 ◽  
Vol 85 (01) ◽  
pp. 114-118 ◽  
Author(s):  
Sandra Wice ◽  
Tilly Ping ◽  
Dieter Herr ◽  
Volker Laux ◽  
Linda Hiebert

SummaryPrevious studies in rats show that unfractionated heparin and the low molecular weight heparin logiparin have a dose-dependent antithrombotic effect and are found in endothelium and plasma when administered orally. Objectives of the present study were to determine if similar evidence of absorption could be observed with oral reviparin sodium. Thrombosis incidence was determined 4 h after application of 10% formalin in methanol to the exposed jugular vein. A dose-dependent antithrombotic effect was observed when 0.01 to 7.5 mg/kg (20 rats/group) was administered by stomach tube immediately following thrombus initiation. Thrombotic incidence was also significantly reduced when 0.025 mg/kg was given 4 and 2 h prior to, immediately after, and 2 and 3 h following thrombus initiation. Reviparin was recovered from endothelium and plasma in trace amounts at all doses. At 0.025 mg/kg, peak aortic endothelial reviparin concentrations were found at 1 and 2 h and peak plasma anti-Xa activity was detected at 2 h. Trace amounts of plasma TFPI were found only at 8 h after administration. Dose-dependent antithrombotic activity and recovery from endothelium and plasma support the hypothesis that orally administered reviparin sodium is absorbed.


2016 ◽  
Vol 8 (4) ◽  
pp. 408-413
Author(s):  
Patrick Emeka ABA

The current study investigated the ameliorative effects of combined therapy of glibenclamide and G. latifolium (GL) on several biochemical parameters of alloxaized Wistar rats. Thirty adult male Wistar rats assigned into 5 groups of 6 rats each were used for the study. Groups 2-5 were intraperitoneally injected with 160 mg/kg of alloxan monohydrate and upon establishment of diabetes (Fasting Blood Glucose (FBG) ≥ 126 mg/dl) were treated with 10 ml/kg distilled water (DW), 2 mg/kg glibenclamide, 200 mg/kg GL and 2 mg/kg glibenclamide and 200 mg/kg GL respectively. Rats in group 1 were not made diabetic and served as normal control. All the treatments were realized through daily oral route using gastric tube, for 21 days. Results indicated that the treatment of diabetic rats with a combination of glibenclamide and GL significantly reduced the elevated glucose levels, cholesterol, triacylglycerol, low density lipoprotein and malondialdehyde levels, along with increases in the high density lipoprotein, glutathione values and catalase activities, when compared to diabetic untreated group. It was concluded that the combined therapy of glibenclamide and GL showed superior antihyperglycemic, hypolipidaemic and antioxidant effects compared to either of them used alone.


Author(s):  
Devang Y. Shelat ◽  
Sanjeev R Acharya

<p><strong>Objective: </strong>Curcumin, is widely studied as a potential drug in treating various disorders but lacks applicability due to poor water solubility and tissue bioavailability. The main objective of the study was to develop a formulation of curcumin that has enhanced water solubility and brain bioavailability.</p><p><strong>Methods: </strong>A curcumin concoction was prepared using solvent evaporation technique taking casein and glutathione as vectors. Various process parameters were identified namely time, temperature, pH and vector while formulation parameters included drug entrapment, anti-oxidant activity, and water solubility. The concoctions were evaluated for <em>in vitro</em> release kinetics at three pH i.e. 1.2, 4.5 and 6.2 at six-time intervals i.e. 10, 20, 30, 40, 60, 120 min using dialysis bag membrane. The same kinetics was further validated using same time points with wistar rats and giving concoction at a single dose of 2 g/kg via the oral route.</p><p><strong>Results: </strong>A concoction i.e. CUR-CA-THIONE having significant entrapment efficiency (77.83%, 97.75%, 90.19%), water solubility (40, 350 and 45 times than normal curcumin) and DPPH activity (IC<sub>50</sub>: 28.91, 25.07 and 27.89) was evaluated in concoctions CUR-CA-THIONE-T.1, CUR-CA-THIONE-T.2 and CUR-CA-THIONE-T.3 respectively. These formulations were then carried out for <em>in vitro</em> release profile at different pH with average release obtained between 20-30 min. <em>In vivo</em> kinetics was studied by isolating tissues like brain, liver, lung, kidney and spleen in male wistar rats and maximum brain bioavailability was observed for CUR-CA-THIONE-T.3 at 30 min with 75 ng/g of brain tissue.</p><p><strong>Conclusion: </strong>The experiment helps in concluding that CUR-CA-THIONE has improved its water solubility and is able to by-pass systemic circulation to targeted activity.</p>


2019 ◽  
Vol 16 (2) ◽  
pp. 38
Author(s):  
Rizky Purboningtyas ◽  
Zahreni Hamzah ◽  
Swasthi Prasetyarini

Bisphenol-A (BPA) is a synthetic chemical substance in the form of monomers which is commonly used as plastic constituents. BPA is often found in household appliances, food and beverage containers, and in dental sealants and acrylic base dentures. BPA can contaminate or enter the human body mostly through oral route or swallowed along with food consumed. It is known that BPA exposure through the oral route can cause several diseases, and one of them is endocrine and metabolic problems, which is Diabetes Mellitus. This study was to analyze the decrease of insulin levels in the liver of male Wistar rats after being exposed by BPA. 18 adult male Wistar rats were divided into 3 groups. Group I (control 1) was not given any treatment, only acclimatized for 7 days. Group II (control 2) was treated with sterile aquadest orally for 28 days. Group III (treatment group) was given oral BPA treatment with a dose of 20 mg / kg body weight for 28 days. After sacrificed, the hepar was homogenated and the insulin level was determined by ELISA. Data were analyzed with One Way Anova test and LSD test. Bisphenol-A (BPA) with a dose of 20 mg/kgBB exposed for 28 days can reduce on hepar insulin levels in adult male Wistar rats.


2016 ◽  
Vol 4 (2) ◽  
pp. 200-212 ◽  
Author(s):  
Abiodun O. Ayoka ◽  
Aderonke K. Ademoye ◽  
Christian E. Imafidon ◽  
Esther O. Ojo ◽  
Ayowole A. Oladele

AIM: To determine the effects of aqueous extract of Allium sativum bulbs (AEASAB) on pituitary-testicular injury and dysfunction in Wistar rats with lead-induced reproductive disturbances.MATERIALS AND METHODS: Male Wistar rats were divided into 7 groups such that the control group received propylene glycol at 0.2 ml/100 g intraperitoneally for 10 consecutive days, the toxic group received lead (Pb) alone at 15 mg/kg/day via intraperitoneal route for 10 days while the treatment groups were pretreated with lead as the toxic group after which they received graded doses of the extract at 50, 100 and 200 mg/kg/day via oral route for 28 days. RESULTS: Pb administration induced significant deleterious alterations in the antioxidant status of the brain and testis, sperm characterization (counts, motility and viability) as well as reproductive hormones (FSH, LH and testosterone) of exposed rats (p < 0.05). These were significantly reversed in the AEASAB-treated groups (p < 0.05). Also, there was marked improvement in the Pb-induced vascular congestion and cellular loss in the pituitary while the observed Pb-induced severe testicular vacuolation was significantly reversed in the representative photomicrographs, following administration of the extract.CONCLUSION: AEASAB treatment ameliorated the pituitary-testicular injury and dysfunction in Wistar rats with Pb-Induced reproductive disturbances.


2020 ◽  
pp. 100-107
Author(s):  
IO Osonuga ◽  
AS Faponle ◽  
EN Ezima ◽  
TK Adenowo ◽  
AA Adelegan

Background: Allium sativum (Garlic) is widely used as a food flavour and it has antimicrobial medicinal purposes. It has other beneficial effects such as improving the cardiovascular and immune systems. The likely effect of garlic on the testicular functions remains controversial. Objective: To investigate the effects of fresh garlic on the fertility of male Wistar rats by quantitative determination of testosterone, follicle-stimulating hormone (FSH), and Luteinizing hormone (LH) levels, as well as the sperm properties. Methods: The aqueous extracts of garlic were administered to the animals through the oral route. Thirty-five male rats were categorized into seven groups, with five rats each distributed as follows: high-dose, medium-dose, low-dose that were administered 750, 500, and 250 mg/kg body weight dosages of the aqueous extracts, respectively. Others were the control group, which received no extract, and the recovery groups received the same doses of the extract. The recovery groups were left for additional twenty-one days without receiving the extract. Results: The results showed an increase in testosterone levels at medium to high-doses of the extract including sustained high levels in recovery groups. Also, there were increases in sperm motility and sperm viability. Conclusions: These findings suggest garlic may play beneficial roles in the reproductive functions of male Wistar rats. The mechanisms for these effects may involve the interplay of many currently unknown factors.


1991 ◽  
Vol 261 (2) ◽  
pp. C305-C309 ◽  
Author(s):  
J. Gorski ◽  
I. Krawczuk ◽  
M. Gorska ◽  
J. Rutkiewicz

This study aimed to examine the extent to which repletion of glycogen in muscles partially depleted of glycogen may be inhibited by contractions and epinephrine. Four experiments were carried out on untrained male Wistar rats. 1) Animals ran 150 min (1,200 m/h) on a treadmill set at +10 degrees incline. After 60, 90, and 120 min of running, they were given glucose (40% solution, 1 ml/100 g) by a stomach tube. 2) Rats ran on a treadmill set as above for 20 min at 3,200 m/h and then 2 h at 800 m/h. 3) In anesthetized rats, gastrocnemius-plantaris muscle group was made to contract isometrically by means of stimulation of the sciatic nerve. The nerve was stimulated with tetanic pulses (7 V, 0.05-ms duration, delivered in 100-ms trains at 100 Hz): first 15 min, 2 pulses/s, then 2 h, 1 pulse/2 s. 4) Epinephrine (0.5 mg/kg) was administered subcutaneously 10 min before onset of stimulation of the sciatic nerve. The nerve was stimulated 15 min with tetanic pulses (as above), 2 pulses/s. Next, rats were rested for 2 h. Level of glycogen was determined in samples of white and red gastrocnemius, plantaris, and soleus. Initial running or stimulation resulted in pronounced glycogen depletion in each muscle. Thereafter, either considerable or full repletion of glycogen occurred in the muscles despite continued contractile activity or the presence of epinephrine. The degree of repletion depended both on the type of muscle and the type of activation of glycogenolysis (running, stimulation of the nerve, epinephrine).(ABSTRACT TRUNCATED AT 250 WORDS)


Author(s):  
I. Stachura ◽  
M. Pardo ◽  
J. Costello ◽  
D.M. Landwehr

Under experimental conditions severe reduction of renal mass results in the hyperfiltration of the remaining nephrons leading to a progressive renal insufficiency. Similar changes are observed in patients with various renal disorders associated with a loss of the functioning nephrons. The progression of renal damage is accelerated by high protein and phosphate intake, and may be modified by the dietary restrictions.We studied 50 five-sixth nephrectarrized male Wistar rats on a standard diet (Rodent Laboratory Chow 5001 Ralston Purina Co., Richmond, Indiana; containing 23.4% protein) over a 20 week period.


Author(s):  
Masoud Nasiri ◽  
Saja Ahmadizad ◽  
Mehdi Hedayati ◽  
Tayebe Zarekar ◽  
Mehdi Seydyousefi ◽  
...  

Abstract. Physical exercise increases free radicals production; antioxidant supplementation may improve the muscle fiber’s ability to scavenge ROS and protect muscles against exercise-induced oxidative damage. This study was designed to examine the effects of all-trans resveratrol supplementation as an antioxidant to mediate anti-oxidation and lipid per-oxidation responses to exercise in male Wistar rats. Sixty-four male Wistar rats were randomly divided into four equal number (n = 16) including training + supplement (TS), training (T), supplement (S) and control (C) group. The rats in TS and S groups received a dose of 10 mg/kg resveratrol per day via gavage. The training groups ran on a rodent treadmill 5 times per week at the speed of 10 m/min for 10 min; the speed gradually increased to 30 m/min for 60 minutes at the end of 12th week. The acute phase of exercise protocol included a speed of 25 m/min set to an inclination of 10° to the exhaustion point. Superoxide dismutase (SOD), glutathione peroxidase (GPx), catalase (CAT) activity, non-enzymatic antioxidants bilirubin, uric acid, lipid peroxidation levels (MDA) and the total antioxidant capacity (TAC) were measured after the exercise termination. The data were analyzed by using one-way ANOVA. The result showed that endurance training caused a significant increase in MDA level [4.5 ± 0.75 (C group) vs. 5.9 ± 0.41 nmol/l (T group)] whereas it decreased the total antioxidant capacity [8.5 ± 1.35 (C group) vs. 7.1 ± 0.55 mmol/l (T group)] (p = 0.001). In addition, GPx and CAT decreased but not significantly (p > 0.05). The training and t-resveratrol supplementation had no significant effect on the acute response of all variables except MDA [4.3 ± 1.4 (C group) vs. 4.0 ± 0.90 nmol/l (TS group)] (p = 0.001) and TAC [8.5 ± 0.90 (C group) vs. 6.6 ± 0.80 mmol/l (TS group)] (p = 0.004). It was concluded that resveratrol supplementation may prevent exercise-induced oxidative stress by preventing lipid peroxidation.


1988 ◽  
Vol 60 (02) ◽  
pp. 133-136 ◽  
Author(s):  
R Schneppenheim ◽  
H Plendl ◽  
U Budde

SummaryA luminescence assay was adapted for detection of von Willebrand factor multimers subsequent to SDS-agarose gel electrophoresis and electroblotting onto nitrocellulose. The method is as fast as chromogenic detection methods and appears to be as sensitive as autoradiography without the disadvantages of the latter.


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