Effects of amiodarone on 5′-deiodination of thyroxine to tri-iodothyronine in rat myocardium

1989 ◽  
Vol 121 (3) ◽  
pp. 431-434 ◽  
Author(s):  
J. A. Ceppi ◽  
A. A. Zaninovich
Keyword(s):  
Body Weight ◽  
Phosphate Buffer ◽  
Wistar Rats ◽  
Type Ii ◽  
Rat Myocardium ◽  
Iopanoic Acid ◽  
Male Wistar Rats ◽  
Expected Increase

ABSTRACT The present work studied the effects of amiodarone (AMD) and iopanoic acid (IA) on the conversion of thyroxine (T4) to tri-iodothyronine (T3) by rat myocardium. In vivo: male Wistar rats weighing 200–250 g were injected i.p. with AMD (2·5 mg/100 g body weight per day for 12 days) or IA (5 mg/100 g body weight every 12 h for 72 h). Hearts were then removed and processed as in the in-vitro studies. In vitro: hearts were homogenized in Krebs–Ringer phosphate buffer (pH 7·4) and AMD (0·1 mmol/l) or IA (10 mmol/l) plus dithiothreitol (8 mmol/l) and 0·01 μCi [125I]T4 or [125I]T3 were added. After incubation for 2 h at 37 °C, radioactive compounds were identified by paper chromatography. Both AMD and IA given in vivo blocked T4 to T3 conversion significantly (P<0·005). When added in vitro, AMD failed to inhibit T4 deiodination to T3 whereas IA induced a significant (P<0·005) decrease in T3 generation. Deiodination of [125I]T3 by heart homogenates was not altered by AMD or IA. While the expected increase in circulating T4 (P< 0·001) and decrease in T3 (P< 0·001) did occur after AMD or IA treatment, plasma TSH in AMD-treated rats was decreased (P<0·001), while in IA-treated animals it was increased (P< 0·001), thus indicating that AMD did not inhibit pituitary type-II 5′-monodeiodinase. In summary, these data suggest that the hypometabolism induced by AMD in rat myocardium through a decrease in the supply of T3 is not responsible for the anti-arrhythmic activity of this drug since IA, which is not an anti-arrhythmic compound, elicited the same effect on cardiac T3. It follows that inhibition of 5′-deiodinase and the anti-arrhythmic activity of AMD are independent properties. Journal of Endocrinology (1989) 121, 431–434

scholarly journals Delving into the Antiurolithiatic Potential of Tribulus terrestris Extract Through –In Vivo Efficacy and Preclinical Safety Investigations in Wistar Rats

2019 ◽  
Vol 9 (1) ◽  
Author(s):  
Jyoti Kaushik ◽  
Simran Tandon ◽  
Rishi Bhardwaj ◽  
Tanzeer Kaur ◽  
Surinder Kumar Singla ◽  
...  
Keyword(s):  
Body Weight ◽  
Aqueous Extract ◽  
Kidney Stones ◽  
Wistar Rats ◽  
Lethal Dose ◽  
Tribulus Terrestris ◽  
Oral Toxicity ◽  
Preclinical Safety

Abstract Modern treatment interventions for kidney stones are wrought with side-effects, hence the need for alternative therapies such as plant-based medicines. We have previously documented through in vitro studies that statistically optimized aqueous extract of Tribulus terrestris (Zygophyllaceae family) possesses antiurolithic and antioxidant potential. This provides strong scientific foundation to conduct in vivo efficacy and preclinical safety studies to corroborate and lend further proof to its ability to prevent and cure kidney stones. The preventive and curative urolithiatic efficacy in experimentally induced nephrolithiatic Wistar rats, along with preclinical toxicity was evaluated following oral administration of statistically optimized aqueous extract of T. terrestris. Treatment showed augmented renal function, restoration of normal renal architecture and increase in body weight. Microscopic analysis of urine revealed excretion of small sized urinary crystals, demonstrating that treatment potentially modulated the morphology of renal stones. Tissue enzymatic estimation affirmed the antioxidant efficacy of treatment with reduced free radical generation. Significant upregulation of p38MAPK at both the gene and protein level was noted in hyperoxaluric group and interestingly treatment reversed it. Acute oral toxicity study established the Median Lethal Dose (LD50) to be greater than 2000 mg/kg body weight (b.wt.) No observed adverse effect level (NOAEL) by repeated oral toxicity for 28 days at 750 mg/kg b.wt. was noted. This study lends scientific evidence to the safe, preventive and curative potential of statistically optimized aqueous extract of T. terrestris at a dose of 750 mg/kg b.wt. and suggests that the extract shows promise as a therapeutic antiurolithic agent.

scholarly journals The in vivo effects of beta-3-receptor agonist CGP-12177 on thyroxine deiodination in cold-exposed, sympathectomized rat brown fat

2000 ◽  
pp. 273-277 ◽  
Author(s):  
D Hofer ◽  
M Raices ◽  
K Schauenstein ◽  
S Porta ◽  
W Korsatko ◽  
...  
Keyword(s):  
Body Weight ◽  
Adipose Tissue ◽  
Receptor Agonist ◽  
Wistar Rats ◽  
Type Ii ◽  
Interscapular Brown Adipose Tissue ◽  
Brown Adipose ◽  
Cgp 12177 ◽  
In Vivo Effects

OBJECTIVE: The effects of the beta-3-receptor agonist CGP-12177 on thyroxine (T4) deiodination in sympathectomized (SX) interscapular brown adipose tissue (BAT) were assessed in 300 g body weight (BW) Wistar rats. DESIGN: Seven days after SX, groups of rats were implanted s.c. with pellets containing 5mg CGP-12177 or 5mg norepinephrine (NE) and were immediately placed at 4 degrees C for 24h. Other SX groups were injected with CGP-12177 or NE 1mg/kg BW i. p. and placed in the cold for 4h. The latter group was injected, in addition, with prazosin 0.4 mg/100g BW i.p. or propranolol 0.5mg/100g BW i.p. 15 min before and 2h after the administration of CGP-12177 or NE. METHODS: Two hours after the last injection of prazosin or propranolol, animals were killed and BAT was removed, homogenized and centrifuged at 500 g for 10 min at 4 degrees C. The infranatants were incubated during 60 min in the presence of dithiothreitol and 1 microCi [(125)I]T4. Aliquots were chromatographed on paper for the measurement of [(125)I]T4 and its deiodinated subproducts. RESULTS: CGP-12177 restored normal T4 deiodination in SX BAT from both groups, but NE was slightly more effective. Propranolol, although not prazosin, blocked the CGP-12177 effects. Contrariwise, the NE-induced rise in deiodination was blocked by prazosin and to a lesser extent by propranolol. CONCLUSIONS: The results indicate that CGP-12177 stimulated the in vivo activation of 5'-deiodinase type II activity predominantly via beta-3-receptor, without participation of alpha-1-receptors.

Concomitant release of sialic acids and calcium by neuraminidase from rat aorta in situ

1988 ◽  
Vol 235 (1279) ◽  
pp. 139-144 ◽  
Keyword(s):  
Sialic Acid ◽  
Wistar Rats ◽  
Rat Aorta ◽  
Sialic Acids ◽  
Molar Ratio ◽  
Male Wistar Rats

Male Wistar rats were heparinized and killed with pentobarbital. The upper and lower ends of the aortae were cannulated and the blood was washed out with saline until the washings contained calcium and sialic-acid-reacting material at minimal concentrations. The aortae were perfused with neuraminidase for 15 min. This caused the appearance of calcium as well as of sialic acids in the perfusate in total amounts of about 5.3 nmol and about 3.6 nmol per aorta respectively. The molar ratio of about 1.5 is sufficiently close to that determined for the association of calcium with sialic acids in vitro to suggest that their association is similar in vivo .

scholarly journals Synthesis of Some Novel Derivatives of 2-(9H-purin-6-ylsulfanyl) Acetohydrazide as Potential Antithyroid Agents

2017 ◽  
Vol 56 (4) ◽  
Author(s):  
Ismat Fatima ◽  
Munawar A. Munawar ◽  
Waqar Nasir ◽  
Misbahul A. Khan ◽  
Affia Tasneem ◽  
...  
Keyword(s):  
Wistar Rats ◽  
Male Wistar Rats ◽  
Antithyroid Agents ◽  
Derivatives Of

Some novel derivatives of 2-(9<em>H</em>-Purin-6-ylsulfanyl)acetohydrazide were synthesized by reacting it with respective aldehydes in ethanol. The antithyroid effect of these compounds was ascertained <em>in vitro</em> by studying their complexation with iodine spectrophotometrically. <em>In vivo</em>, the hormonal as well as histological variations in male Wistar rats demonstrated significant antithyroid potential (p ≤ 0.05) of these compounds.

scholarly journals In vitro (anti-alpha-glucosidase) activity and in vivo anti-diabetic activity of Androsace foliosa (common rock jasmine) in alloxan-induced diabetic BALB/c mice

2019 ◽  
Vol 17 ◽  
pp. 205873921985742
Author(s):  
Jawad Zaheer ◽  
Qazi Najam-Us-Saqib ◽  
Misba Qamar ◽  
Muhammad Akram
Keyword(s):  
Body Weight ◽  
Inhibitory Concentration ◽  
Methanolic Extract ◽  
Type Ii ◽  
Standard Drug ◽  
Diabetes Mellitus Type Ii ◽  
Reduce Body Weight ◽  
Alpha Glucosidase

Androsace foliosa syn. Androsace sarmentosa (botanical name of common rock jasmine) ( Primulaceae) is used in the treatment various disorders. The aim of this study is to evaluate in vitro anti-diabetic activity of crude methanolic extract of leaves and roots of A. foliosa by anti -alpha-glucosidase (α-Glc) and in vivo anti-diabetic activity of n-hexane fraction on alloxan-induced diabetic mice. Results of in vitro anti-diabetic (α-Glc) activity showed that n-hexane leaves fraction was most potent among all the fractions and showed IC50 (half maximal inhibitory concentration) value of 64.91 ± 0.16 µg and % inhibition of 89.35 ± 0.45, comparable to that of standard acarbose. In vivo n-hexane leaves fraction decreases blood glucose level and reduces body weight similar to that of standard drug glibenclamide. Based on the conclusion of both in vitro and in vivo activities, it can be accomplished that the plant A. foliosa acquires noteworthy anti-diabetic action and can be used to treat diabetes mellitus type II and to reduce body weight.

scholarly journals CUR-CA-THIONE: A NOVEL CURCUMIN CONCOCTION WITH ENHANCED WATER SOLUBILITY AND BRAIN BIO-AVAILABILITY

2016 ◽  
Vol 8 (12) ◽  
pp. 265 ◽  
Author(s):  
Devang Y. Shelat ◽  
Sanjeev R Acharya
Keyword(s):  
Wistar Rats ◽  
Water Solubility ◽  
Release Kinetics ◽  
Entrapment Efficiency ◽  
Systemic Circulation ◽  
Oral Route ◽  
Male Wistar Rats ◽  
Dialysis Bag

<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>

scholarly journals Endothelium/Nitric Oxide Mediates the Vasorelaxant and Antihypertensive Effects of the Aqueous Extract from the Stem Bark ofMammea africanaSabine (Guttiferae)

2012 ◽  
Vol 2012 ◽  
pp. 1-8 ◽  
Author(s):  
Elvine Pami Nguelefack-Mbuyo ◽  
Alain Bertrand Dongmo ◽  
Télesphore Benoît Nguelefack ◽  
Albert Kamanyi ◽  
Pierre Kamtchouing ◽  
...  
Keyword(s):  
Aqueous Extract ◽  
Response Curve ◽  
Wistar Rats ◽  
Antihypertensive Effect ◽  
Stem Bark ◽  
Male Wistar Rats ◽  
Vasorelaxant Activity ◽  
Concentration Response Curve

This study evaluates the vasorelaxant and antihypertensive effects of the aqueous extract from the stem bark ofM. africana(AEMA). AEMA was testedin vitroon intact or endothelium-denuded rats’ aorta rings precontracted with KCl or norepinephrine in absence or in presence of L-NAME or glibenclamide. The effect of a single concentration (300 μg/mL) of AEMA was also examined on the concentration-response curve of KCl.In vivo, the antihypertensive effects of AEMA (200 mg/kg/day) were evaluated in male Wistar rats treated with L-NAME (40 mg/kg/day) for 4 weeks. AEMA relaxed aorta rings precontracted with NE or KCl with respective EC50 values of 0.36 μg/mL and 197.60 μg/mL. The destruction of endothelium or pretreatment of aorta rings with L-NAME shifted the EC50 of AEMA from 0.36 μg/mL to 40.65 μg/mL and 20.20 μg/mL, respectively. The vasorelaxant activity ofM. africanawas significantly inhibited in presence of glibenclamide. AEMA also significantly inhibited the concentration-response curve of KCl. Administered orally, AEMA induced acute and chronic antihypertensive effects and normalized renal NO level. These results show that the vasorelaxant activity of AEMA might be mediated by the activation of the NO-cGMP-ATP-dependent potassium channels pathway and might predominantly account for its antihypertensive effect.

Evidence suggesting that cadmium induces a non-thyroidal illness syndrome in the rat

1997 ◽  
Vol 154 (1) ◽  
pp. 113-117 ◽  
Author(s):  
M A Pavia ◽  
B Paier ◽  
M I Noli ◽  
K Hagmüller ◽  
A A Zaninovich
Keyword(s):  
Body Weight ◽  
Wistar Rats ◽  
Turnover Rate ◽  
Metabolic Clearance ◽  
Metabolic Clearance Rate ◽  
Normal Response ◽  
Stimulation Of ◽  
Fractional Turnover

Abstract The effect of in vivo administration of cadmium chloride on the pituitary-thyroidal axis was assessed in 200 g body weight Wistar rats. A dose of 2·5 mg/kg body weight was injected i.v. 24 h before the experiments were initiated. Plasma thyroxine (T4) and tri-iodothyronine (T3) concentrations in cadmium-treated rats were significantly (P<0·01) decreased, whereas plasma TSH failed to increase in response to low T4 and T3. However, the TSH response to TRH and the pituitary content of TSH in these rats were both normal. Cadmium induced a significant (P<0·01) decrease in 4-h thyroidal 131I uptake and in thyroid/plasma radioactivity ratio. The in vitro conversion of T4 to T3 in the pituitary was significantly (P<0·01) blocked by cadmium whereas there was no in vivo effect. Parameters of peripheral T4 kinetics in cadmium-treated rats, such as metabolic clearance rate (P<0·01), fractional turnover rate (P<0·01), absolute disposal rate (P<0·05), urinary clearance (P<0·05) and faecal clearance (P<0·05), were all decreased by cadmium. The lack of response of TSH to low plasma T4 and T3 and the normal response to exogenous TRH in this and in other non-thyroidal illness syndromes produced by other pathologies suggest a decreased stimulation of pituitary thyrotrophs by endogenous TRH. Journal of Endocrinology (1997) 154, 113–117

N-acetylcysteine does not protect against type II cell injury after prolonged exposure to hyperoxia in rats

1997 ◽  
Vol 273 (3) ◽  
pp. L548-L555 ◽  
Author(s):  
R. J. van Klaveren ◽  
D. Dinsdale ◽  
J. L. Pype ◽  
M. Demedts ◽  
B. Nemery
Keyword(s):  
Cell Injury ◽  
Prolonged Exposure ◽  
Antioxidant Properties ◽  
Exposed Group ◽  
Type Ii Cells ◽  
Type Ii ◽  
Male Wistar Rats ◽  
Hyperoxic Lung Injury

Although the antioxidant properties of N-acetylcysteine (NAC) in vitro are widely accepted, the efficacy of NAC in the prevention of O2 toxicity in vivo is poorly documented. The aim of our study was to investigate the presumed protective effect of NAC on hyperoxic lung injury, focusing on gamma-glutamyltransferase (gamma-GT) activity and glutathione (GSH) levels in lung tissue, epithelial lining fluid (ELF), and isolated rat type II cells immediately after their isolation and 48 h later when kept in culture in normoxia. Thirty-four male Wistar rats were divided in three groups (n = 10-14) and were exposed to air or to 60 or 85% O2 for 7 days. One-half of the rats in each group received 200 mg/kg NAC intraperitoneally one time per day from 3 days before exposure until the end of the experiment, and the other one-half received the vehicle. In the 85% O2-exposed animals, NAC led to more respiratory distress and weight loss. NAC did not prevent the rise in bronchoalveolar lavage lactate dehydrogenase and alkaline phosphatase, but it did prevent the rise in calculated ELF volume. NAC decreased GSH levels (1.4-fold) and gamma-GT activity (1.8-fold) in the air-exposed type II cells. In the 60% O2-exposed group, no effects of NAC were seen (except for a decrease in gamma-GT mRNA expression), but, in the 85% O2-exposed group, NAC gave rise to higher GSH (2.6-fold) and higher gamma-GT activity (2.9-fold) in the ELF and lower GSH (6.9-fold) and higher gamma-GT activity (3.6-fold) in the type II cells. Even in culture, GSH levels remained 1.5-fold lower than in the cells from the air-exposed animals and 2-fold lower than in the cells from the 85% O2-exposed animals. There was increased DNA damage (as assessed by thymidine incorporation) and apoptosis after hyperoxia, especially after 60% O2, and this effect was amplified after NAC treatment. Although protective at the endothelial side, NAC treatment led to adverse effects at the epithelial side, despite, or probably because of, restoration of the ELF GSH levels in the presence of high O2 levels. Because NAC is rapidly metabolized to cysteine, it is plausible that the effects of NAC are manifested through the toxic effects of cysteine.

scholarly journals Protective Effect of Methylxanthine Fractions Isolated from Bancha Tea Leaves against Doxorubicin-Induced Cardio- and Nephrotoxicities in Rats

2020 ◽  
Vol 2020 ◽  
pp. 1-9
Author(s):  
Maya P. Radeva-Ilieva ◽  
Kaloyan D. Georgiev ◽  
Nadezhda R. Hvarchanova ◽  
Stanila S. Stoeva ◽  
Iliya J. Slavov ◽  
...  
Keyword(s):  
Oxidative Stress ◽  
Body Weight ◽  
Tissue Damage ◽  
Histological Analysis ◽  
Concomitant Administration ◽  
Renal Tissue ◽  
Creatinine Kinase ◽  
Male Wistar Rats

Doxorubicin is an anthracycline antibiotic that is used for the treatment of various types of cancer. However, its clinical usage is limited due to its potential life-threatening adverse effects, such as cardio- and nephrotoxicities. Nonetheless, simultaneous administration of doxorubicin and antioxidants, such as those found in green tea leaves, could reduce cardiac and renal tissue damage caused by oxidative stress. The methylxanthine fraction isolated from Bancha tea leaves were tested in vitro for its antioxidant activity and in vivo for its organoprotective properties against doxorubicin-induced cardio- and nephrotoxicities in a rat model. The in vivo study was conducted on male Wistar rats divided into 6 groups. Methylxanthines were administered at high (5 mg/kg body weight) and low (1 mg/kg body weight) doses, while doxorubicin was administered at a cumulative dose of 20 mg/kg body weight. Serum creatinine, uric acid, and urea concentrations, as well as serum enzyme levels (creatinine kinase (CK), creatinine kinase MB fraction (CK-MB), aspartate aminotransferase (AST), and lactate dehydrogenase (LDH)) and electrolytes (Na+, K+, and Cl-), were analysed. In addition, histological analysis was performed to assess cardiac and renal tissue damage. The concomitant administration of Bancha methylxanthines and doxorubicin showed a dose-dependent reduction in the serum biochemical parameters, indicating a decrease in the cardiac and renal tissue damage caused by the antibiotic. Histological analysis showed that pretreatment with methylxanthines at the dose of 5 mg/kg resulted in an almost normal myocardial structure and a significant decrease in the morphological kidney changes caused by doxorubicin exposure compared with the group that received doxorubicin alone. The putative mechanism is most likely related to a reduction in the oxidative stress caused by doxorubicin.

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