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

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.

Direct Na+-K+ pump stimulation by K+ in cortical collecting tubules: a mechanism for early renal K+ adaptation

1989 ◽  
Vol 257 (4) ◽  
pp. F595-F601 ◽  
Author(s):  
Y. Fujii ◽  
A. I. Katz
Keyword(s):  
Turnover Rate ◽  
Rapid Rise ◽  
Hormonal Factors ◽  
Collecting Tubule ◽  
Collecting Tubules ◽  
Stimulation Of ◽  
External K ◽  
Cortical Collecting Tubule

To evaluate the mechanism of increased Na+-K+ pump turnover rate that characterizes the early cortical collecting tubule (CCT) response to K+ loading [Y. Fujii, S. K. Mujais, and A. I. Katz. Am. J. Physiol. 256 (Renal Fluid Electrolyte Physiol. 25): F279-F284, 1989.], we measured ouabain-sensitive 86Rb+ uptake in microdissected rat CCT exposed acutely to elevated ambient K+ in vivo and in vitro. Tubules preincubated in 10 mM K+ had higher 86Rb+ uptake than when preincubated in 5 mM K+ (25.9 +/- 1.2 vs. 18.9 +/- 0.7 pmol.mm-1.min-1, P less than 0.001). KCl infusion (5 mumol.100 g-1.min-1 x 60 min) increased 86Rb+ uptake from 19.2 +/- 1.0 to 31.2 +/- 1.4 pmol.mm-1.min-1, P less than 0.001; the increment was preserved in tubules subsequently treated with monensin or nystatin in vitro, suggesting that pump stimulation was not mediated by increased cell Na+. This conclusion was confirmed in separate experiments in which the effect of K+ on 86Rb+ uptake was not altered by concurrent preincubation with amiloride. Studies with CCT from isolated perfused kidneys and from adrenalectomized animals revealed that stimulation of 86Rb+ uptake by a K+ load occurs rapidly (less than or equal to 5 min) and is independent of hormonal factors. Increased external K+ produces a rapid rise in K+-transporting capacity (turnover rate) of the Na+-K+ pump in CCT. This phenomenon probably represents a direct effect on K+ on the pump and is an important component of the early renal response to increased K+ secretory load.

In-vitro and in-vivo responses to chicken LHRH-I and chicken LHRH-II in male turkeys (Meleagris gallopavo)

1992 ◽  
Vol 132 (3) ◽  
pp. 387-393 ◽  
Author(s):  
D. Guémené ◽  
J. B. Williams
Keyword(s):  
Body Weight ◽  
Single Dose ◽  
Meleagris Gallopavo ◽  
Initial Increase ◽  
Prolonged Action ◽  
The Difference ◽  
High Doses ◽  
Stimulation Of

ABSTRACT Stimulation of male turkey hypophyses in vitro with chicken (c)LHRH-I, cLHRH-II or porcine (p)LHRH (0·1 μmol/l) using a perifusion technique caused an increase in the release of LH. In this system, cLHRH-II was approximately 2·5-fold more potent than cLHRH-I and pLHRH which were equipotent. The difference was due to a greater amplitude of the response but not to a prolonged action. Hypophyseal desensitization to a subsequent stimulation was induced when the interval between stimulations was 30 min, but did not occur when lengthened to 60 or 120 min. Injection of a single dose of cLHRH-I or -II in vivo at doses of 10 and 0·1 nmol/kg body weight stimulated increases in the plasma concentration of LH and testosterone initiated within 1 or 10 min after injection respectively. As in vitro, cLHRH-II induced greater responses, which were dose-related, than did cLHRH-I. However, this difference could be attributed to a greater potency of cLHRH-II and to a more prolonged action. At the 10 nmol/kg dose, the shape of the LH response to cLHRH-II changed; it consisted of an initial increase during 10 min after injection, followed by a more sustained phase during which LH levels were still increasing between 20 and 60 min after injection. In contrast, after an injection of cLHRH-I at doses of 10 or 0·1 nmol/kg or cLHRH-II at a dose of 0·1 nmol/kg, LH levels were at a peak within 5 min and thereafter declined gradually. This decrease in LH may therefore simply be related to the disappearance of the LHRH from the circulation or to other unknown actions of cLHRH-II, when high doses are used. Journal of Endocrinology (1992) 132, 387–393

Role of natriuretic peptide clearance receptor in in vivo control of C-type natriuretic peptide

1995 ◽  
Vol 269 (1) ◽  
pp. H326-H331 ◽  
Author(s):  
R. R. Brandt ◽  
D. M. Heublein ◽  
L. L. Aarhus ◽  
J. A. Lewicki ◽  
J. C. Burnett
Keyword(s):  
Natriuretic Peptide ◽  
Clearance Rate ◽  
Metabolic Clearance ◽  
Binding Assays ◽  
Metabolic Clearance Rate ◽  
Amino Acid Peptide ◽  
Cardiovascular Actions ◽  
Clearance Receptor

C-type natriuretic peptide (CNP) is a newly described 22-amino acid peptide of endothelial cell origin, which has selective cardiovascular actions and is structurally related to atrial natriuretic peptide (ANP). Recent in vitro studies have demonstrated that an important regulatory pathway for the clearance of natriuretic peptides involves binding to a common clearance receptor [natriuretic peptide C receptor (NPR-C)]. Although CNP has also been identified as a ligand for NPR-C in binding assays, no studies have defined the in vivo interaction of CNP with NPR-C. CNP (10 ng.kg-1.min-1) followed by C-ANP-(4-23), a specific ligand for NPR-C blockade, was infused intravenously in two groups (both n = 7) of anesthetized dogs at two different doses (0.1 or 1.0 micrograms.kg-1.min-1) to permit calculation of total metabolic clearance rate (TMCR). C-ANP-(4-23) increased circulating CNP and reduced TMCR in both groups. Pulmonary metabolic clearance rate was negative at baseline, suggesting a net secretion of CNP across the lung, which was increased during CNP infusion and was abolished with NPR-C blockade. Renal and femoral metabolic clearance rates were positive at baseline and increased with CNP infusion. A decrease in cardiac output and cardiac filling pressures in response to CNP administration was potentiated by NPR-C blockade. We conclude that 1) circulating CNP achieved by CNP infusion is regulated by NPR-C in vivo, 2) the pulmonary circulation is a possible site of CNP secretion, 3) the renal and peripheral circulations are sites of CNP clearance, and 4) NPR-C blockade potentiates the selective cardiovascular actions of CNP.

Ketone body turnover during and after exercise in overnight-fasted and starved humans

1983 ◽  
Vol 245 (4) ◽  
pp. E318-E325 ◽  
Author(s):  
F. Fery ◽  
E. O. Balasse
Keyword(s):  
Clearance Rate ◽  
Ketone Body ◽  
Turnover Rate ◽  
Ketone Bodies ◽  
Sharp Contrast ◽  
Metabolic Clearance ◽  
Metabolic Clearance Rate ◽  
Initial Degree ◽  
Stimulation Of ◽  
Marked Drop

The concentration of ketone bodies and their rate of transport (estimated with an infusion of beta-[14C]-hydroxybutyrate) were determined before, during, and after exercise in overnight-fasted and 3- to 5-day-fasted subjects who walked on a treadmill for 2 h at approximately 50% of their VO2max. In overnight-fasted subjects, exercise increased the rate of turnover (+125% after 2 h) and the metabolic clearance rate of ketone bodies whose concentration rose from 0.20 to 0.39 mM. Discontinuation of exercise was associated with a marked increase in ketone levels (+0.73 mM after 30 min of recovery) that was related to a further stimulation of ketogenesis (+19%) and to a marked drop of the metabolic clearance rate to below preexercise values. In sharp contrast with overnight-fasted subjects, starved subjects (with a resting ketone level averaging 5.7 mM) responded to work by a decrease in the turnover rate and in the concentration of ketones, their metabolic clearance rate remaining unchanged. Thus, the response of ketogenesis and muscular ketone uptake to exercise are both markedly influenced by the initial degree of fasting ketosis.

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

Thrombopoietin-Induced Stimulation of Megakaryocyte- Enriched Bone Marrow Cultures

1979 ◽  
Author(s):  
K. L. Kellar ◽  
B. L. Evatt ◽  
C. R. McGrath ◽  
R. B. Ramsey
Keyword(s):  
Bone Marrow ◽  
Dna Synthesis ◽  
Bone Marrow Cells ◽  
Rabbit Plasma ◽  
Bone Marrow Cultures ◽  
Plasma Fractions ◽  
Marrow Cultures ◽  
Stimulation Of

Liquid cultures of bone marrow cells enriched for megakaryocytes were assayed for incorporation of 3H-thymidine (3H-TdR) into acid-precipitable cell digests to determine the effect of thrombopoietin on DNA synthesis. As previously described, thrombopoietin was prepared by ammonium sulfate fractionation of pooled plasma obtained from thrombocytopenic rabbits. A control fraction was prepared from normal rabbit plasma. The thrombopoietic activity of these fractions was determined in vivo with normal rabbits as assay animals and the rate of incorporation of 75Se-selenomethionine into newly formed platelets as an index of thrombopoietic activity of the infused material. Guinea pig megakaryocytes were purified using bovine serum albumin gradients. Bone marrow cultures containing 1.5-3.0x104 cells and 31%-71% megakaryocytes were incubated 18 h in modified Dulbecco’s MEM containing 10% of the concentrated plasma fractions from either thrombocytopenic or normal rabbits. In other control cultures, 0.9% NaCl was substituted for the plasma fractions. 3H-TdR incorporation was measured after cells were incubated for 3 h with 1 μCi/ml. The protein fraction containing thrombopoietin-stimulating activity caused a 25%-31% increase in 3H-TdR incorporation over that in cultures which were incubated with the similar fraction from normal plasma and a 29% increase over the activity in control cultures to which 0.9% NaCl had been added. These data suggest that thrombopoietin stimulates DNA synthesis in megakaryocytes and that this tecnique may be useful in assaying thrombopoietin in vitro.

scholarly journals Anti-Obesity and Anti-Adipogenic Effects of Chitosan Oligosaccharide (GO2KA1) in SD Rats and in 3T3-L1 Preadipocytes Models

Molecules ◽  
2021 ◽  
Vol 26 (2) ◽  
pp. 331
Author(s):  
Jung-Yun Lee ◽  
Tae Yang Kim ◽  
Hanna Kang ◽  
Jungbae Oh ◽  
Joo Woong Park ◽  
...  
Keyword(s):  
Gene Expression ◽  
Body Weight ◽  
Density Lipoprotein ◽  
Treated Group ◽  
Control Group ◽  
Chitosan Oligosaccharide ◽  
Sd Rats ◽  
Adipogenic Gene

Excess body weight is a major risk factor for type 2 diabetes (T2D) and associated metabolic complications, and weight loss has been shown to improve glycemic control and decrease morbidity and mortality in T2D patients. Weight-loss strategies using dietary interventions produce a significant decrease in diabetes-related metabolic disturbance. We have previously reported that the supplementation of low molecular chitosan oligosaccharide (GO2KA1) significantly inhibited blood glucose levels in both animals and humans. However, the effect of GO2KA1 on obesity still remains unclear. The aim of the study was to evaluate the anti-obesity effect of GO2KA1 on lipid accumulation and adipogenic gene expression using 3T3-L1 adipocytes in vitro and plasma lipid profiles using a Sprague-Dawley (SD) rat model. Murine 3T3-L1 preadipocytes were stimulated to differentiate under the adipogenic stimulation in the presence and absence of varying concentrations of GO2KA1. Adipocyte differentiation was confirmed by Oil Red O staining of lipids and the expression of adipogenic gene expression. Compared to control group, the cells treated with GO2KA1 significantly decreased in intracellular lipid accumulation with concomitant decreases in the expression of key transcription factors, peroxisome proliferator-activated receptor gamma (PPARγ) and CCAAT/enhancer-binding protein alpha (CEBP/α). Consistently, the mRNA expression of downstream adipogenic target genes such as fatty acid binding protein 4 (FABP4), fatty acid synthase (FAS), were significantly lower in the GO2KA1-treated group than in the control group. In vivo, male SD rats were fed a high fat diet (HFD) for 6 weeks to induced obesity, followed by oral administration of GO2KA1 at 0.1 g/kg/body weight or vehicle control in HFD. We assessed body weight, food intake, plasma lipids, levels of alanine aminotransferase (ALT) and aspartate aminotransferase (AST) for liver function, and serum level of adiponectin, a marker for obesity-mediated metabolic syndrome. Compared to control group GO2KA1 significantly suppressed body weight gain (185.8 ± 8.8 g vs. 211.6 ± 20.1 g, p < 0.05) with no significant difference in food intake. The serum total cholesterol, triglyceride, and low-density lipoprotein (LDL) levels were significantly lower in the GO2KA1-treated group than in the control group, whereas the high-density lipoprotein (HDL) level was higher in the GO2KA1 group. The GO2KA1-treated group also showed a significant reduction in ALT and AST levels compared to the control. Moreover, serum adiponectin levels were significantly 1.5-folder higher than the control group. These in vivo and in vitro findings suggest that dietary supplementation of GO2KA1 may prevent diet-induced weight gain and the anti-obesity effect is mediated in part by inhibiting adipogenesis and increasing adiponectin level.

scholarly journals Contamination of erythropoietin by endotoxin: in vivo and in vitro effects on murine erythropoiesis

Blood ◽  
1979 ◽  
Vol 54 (1) ◽  
pp. 146-158 ◽  
Author(s):  
KS Zuckerman ◽  
PJ Quesenberry ◽  
J Levin ◽  
R Sullivan
Keyword(s):  
Significant Inhibition ◽  
Erythropoietic Activity ◽  
Limulus Amebocyte Lysate ◽  
Endogenous Erythropoietin ◽  
Significant Change ◽  
In Vitro Effects ◽  
Stimulation Of

Abstract Endotoxin was detected in all erythropoietin preparations tested and was removed from four lots, without loss of erythropoietic activity, by adsorption with limulus amebocyte lysate. Comparison of adsorbed (endotoxin-depleted) and nonadsorbed (endotoxin-containing) erythropoietin preparations demonstrated significant inhibition of CFU- e and BFU-e in vitro by nonadsorbed erythropoietin at concentrations higher than 0.25 U/ml and 2.0 U/ml, respectively. CFU-e and BFU-e were inhibited significantly by readdition in vitro of 10(-5)-10(-3) mug of endotoxin per unit of limulus-adsorbed erythropoietin. Administration of saline or 6 U of nonadsorbed or adsorbed erythropoietin twice a day for 4 days of CF1 mice resulted in reticulocyte counts of 2.1%, 9.9%, and 15.9%, respectively. Nonadsorbed erythropoietin resulted in a 29% decrease in erythropoiesis, a 42% decrease in CFU-e, and a 16% increase in granulopoiesis in the marrow, whereas adsorbed erythropoietin caused a 28% increase in erythropoiesis, no significant change in CFU-e and a 19% decrease in granulopoiesis in the marrow. Both preparations resulted in marked increases in splenic erythropoiesis and granulopoiesis. The effects of adsorbed erythropoietin are similar to those produced following stimulation of hematopoiesis by endogenous erythropoietin. Hemopoietic changes induced by nonadsorbed erythropoietin in vivo and in vitro are affected substantially by contamination of the erythropoietin preparations with endotoxin.

scholarly journals The Novel Arylamidine T-2307 MaintainsIn VitroandIn VivoActivity against Echinocandin-Resistant Candida albicans

2014 ◽  
Vol 59 (2) ◽  
pp. 1341-1343 ◽  
Author(s):  
Nathan P. Wiederhold ◽  
Laura K. Najvar ◽  
Annette W. Fothergill ◽  
Rosie Bocanegra ◽  
Marcos Olivo ◽  
...  
Keyword(s):  
Body Weight ◽  
Candida Albicans ◽  
Invasive Candidiasis ◽  
Placebo Control ◽  
The Novel ◽  
Content Type ◽  
Fungal Burden ◽  
Potential Use

ABSTRACTWe evaluated thein vitroandin vivoactivities of the investigational arylamidine T-2307 against echinocandin-resistantCandida albicans. T-2307 demonstrated potentin vitroactivity, and daily subcutaneous doses between 0.75 and 6 mg/kg of body weight significantly improved survival and reduced fungal burden compared to placebo control and caspofungin (10 mg/kg/day) in mice with invasive candidiasis caused by an echinocandin-resistant strain. Thus, T-2307 may have potential use in the treatment of echinocandin-resistantC. albicansinfections.

Sign in / Sign up

Export Citation Format

Share Document