Kinetic impairment of nitrogen and muscle glutamine metabolisms in old glucocorticoid-treated rats

1999 ◽  
Vol 276 (3) ◽  
pp. E558-E564 ◽  
Author(s):  
Regine Minet-Quinard ◽  
Christophe Moinard ◽  
Françoise Villie ◽  
Stephane Walrand ◽  
Marie-Paule Vasson ◽  
...  

Aged rats are more sensitive to injury, possibly through an impairment of nitrogen and glutamine (Gln) metabolisms mediated by glucocorticoids. We studied the metabolic kinetic response of adult and old rats during glucocorticoid treatment. The male Sprague-Dawley rats were 24 or 3 mo old. Both adult and old rats were divided into 7 groups. Groups labeled G3, G5, and G7 received, by intraperitoneal injection, 1.50 mg/kg of dexamethasone (Dex) for 3, 5, and 7 days, respectively. Groups labeled G3PF, G5PF, and G7PF were pair fed to the G3, G5, or G7 groups and were injected with an isovolumic solution of NaCl. One control group comprised healthy rats fed ad libitum. The response to aggression induced specifically by Dex (i.e., allowing for variations in pair-fed controls) appeared later in the aged rats (decrease in nitrogen balance from day 1 in adults but only from day 4 in old rats). The adult rats rapidly adapted to Dex treatment, whereas the catabolic state worsened until the end of treatment in the old rats. Gln homeostasis was not maintained in the aged rats; despite an early increase in muscular Gln synthetase activity, the Gln pool was depleted. These results suggest a kinetic impairment of both nitrogen and muscle Gln metabolisms in response to Dex with aging.

2004 ◽  
Vol 287 (4) ◽  
pp. E671-E676 ◽  
Author(s):  
R. Minet-Quinard ◽  
C. Moinard ◽  
F. Villie ◽  
M. P. Vasson ◽  
L. Cynober

An impairment of muscle glutamine metabolism in response to dexamethasone (DEX) occurs with aging. To better characterize this alteration, we have investigated muscle glutamine release with regard to muscle glutamine production (net protein breakdown, de novo glutamine synthesis) in adult and old glucocorticoid-treated rats. Male Sprague-Dawley rats (3 or 24 mo old) were divided into seven groups: three groups received 1.5 mg/kg of DEX once a day by intraperitoneal injection for 3, 5, or 7 days; three groups were pair fed to the three treated groups, respectively; and one control group of healthy rats was fed ad libitum. Muscle glutamine synthetase activity increased earlier in old rats ( day 3) than in adult rats ( day 7), whereas an increase in muscle glutamine release occurred later in old rats ( day 5) than in adult DEX-treated rats ( day 3). Consequently, muscle glutamine concentration decreased later in old rats ( day 5) than in adults ( day 3). Finally, net muscle protein breakdown increased only in old DEX-treated rats ( day 7). In conclusion, the impairment of muscle glutamine metabolism is due to a combination of an increase in glutamine production and a delayed increase in glutamine release.


2000 ◽  
Vol 88 (6) ◽  
pp. 2023-2030 ◽  
Author(s):  
S. A. Shore ◽  
J. H. Abraham ◽  
I. N. Schwartzman ◽  
G. G. Krishna Murthy ◽  
J. D. Laporte

During ozone (O3) exposure, adult rats decrease their minute ventilation (V˙e). To determine whether such changes are also observed in immature animals, Sprague-Dawley rats, aged 2, 4, 6, 8, or 12 wk, were exposed to O3(2 ppm) in nose-only-exposure plethysmographs. BaselineV˙e normalized for body weight decreased with age from 2.1 ± 0.1 ml ⋅ min−1⋅ g−1in 2-wk-old rats to 0.72 ± 0.03 ml ⋅ min−1⋅ g−1in 12-wk-old rats, consistent with the higher metabolic rates of younger animals. In adult (8- and 12-wk-old) rats, O3caused 40–50% decreases in V˙e that occurred primarily as the result of a decrease in tidal volume. In 6-wk-old rats, O3-induced changes inV˙e were significantly less, and in 2- and 4-wk-old rats, no significant changes inV˙e were observed during O3exposure. The increased baseline V˙e and the smaller decrements in V˙e induced by O3in the immature rats imply that their delivered dose of O3is much higher than in adult rats. To determine whether these differences in O3dose influence the extent of injury, we measured bronchoalveolar lavage protein concentrations. The magnitude of the changes in bronchoalveolar lavage induced by O3was significantly greater in 2- than in 8-wk-old rats (267 ± 47 vs. 165 ± 22%, respectively, P < 0.05). O3exposure also caused a significant increase in PGE2in 2-wk-old but not in adult rats. The results indicate that the ventilatory response to O3is absent in 2-wk-old rats and that lack of this response, in conjunction with a greater specific ventilation, leads to greater lung injury.


1995 ◽  
Vol 269 (6) ◽  
pp. H2017-H2021 ◽  
Author(s):  
S. Verma ◽  
S. Bhanot ◽  
J. H. McNeill

Evidence suggests that hyperinsulinemia may be causally related to the development of high blood pressure (BP) in fructose-hypertensive (FH) rats. Because plasma insulin has been shown to modulate endothelin (ET) release in vivo, we hypothesized that hyperinsulinemia may provide a continual stimulus for ET release, which could increase BP by altering plasma or blood vessel ET levels. To test this hypothesis, we studied the effect of chronic ET-receptor blockade (by using bosentan, a noncompetitive ET antagonist) on plasma insulin levels, plasma ET levels, blood vessel ET content, and BP in FH rats. Chronic oral bosentan treatment (100 mg.kg-1.day-1) was initiated in 6-wk-old Sprague-Dawley rats. One week after bosentan treatment was started, rats were fed either normal rat chow or a fructose-enriched diet. Plasma insulin, plasma glucose, and systolic BP were measured weekly. At termination (in 15-wk-old rats), plasma ET levels and total mesenteric ET content were determined. Bosentan treatment caused a sustained decrease in BP in the FH rats (treated 130 +/- 4 vs. untreated 149 +/- 2 mmHg, P < 0.001) but had no effect in the normotensive control group. FH rats had a higher total mesenteric ET content compared with the control group (21.5 +/- 3.2 vs. 14.1 +/- 2.1 fmol, P < 0.05). Bosentan treatment did not alter total mesenteric ET content (treated 18.8 +/- 5 fmol, P > 0.05 vs. untreated) nor did it affect plasma insulin or ET levels in any group. These data suggest that ET may be involved in the development of high BP in FH rats. Whether ET represents an intermediate, linking hyperinsulinemia to hypertension in rats, or is an independent hypertensinogenic mechanism remains to be determined.


PLoS ONE ◽  
2021 ◽  
Vol 16 (7) ◽  
pp. e0243108
Author(s):  
Yafang Li ◽  
Yiqiang Qiao ◽  
Huanhuan Wang ◽  
Zao Wang

In recent years, many studies have found that mechanical tension can activiate NF-kB signal pathway and NF-kB plays an important role in the process of osteogenesis. However, it is still unclear whether this process exists in the anterior palatal suture expansion. In this paper, we mainly studied the effect of intraperitoneal injection of PDTC on the NF-kB signaling pathway and osteogenesis index of the anterior palatal suture expansion model in young adult rats. The expansion model is grouped and established: 45 male 8-week-old Sprague-Dawley rats were randomly divided into three groups, an expansion only (EO) group, an expansion plus PDTC (PE) group, and a control group. The results revealed that PDTC inhibited the activity of NF-kB signaling pathway and promote one morphogenetic protein 2 (BMP-2), steocalatin (OCN) expression. Compared with the control group, the optical density (OD) value of BMP in the EO group and PE group rats increased significantly from the first day to the seventh day, and the difference was statistically significant (P<0.05). After 6.0Gy irradiation, PDTC administration group could slightly increase the total SOD level in the liver and serum of rats, and reduce the MDA level in the liver and serum, especially the effect of 60mg/kg and 90mg/kg was the most obvious.


1991 ◽  
Vol 260 (6) ◽  
pp. E933-E937 ◽  
Author(s):  
J. Fox ◽  
M. B. Mathew

Plasma immunoreactive parathyroid hormone (irPTH) levels increase and renal responsiveness to pharmacological doses of PTH decreases with advancing age. This study tested whether 1) decreased irPTH clearance contributes to the elevated NH2-terminal irPTH levels seen in aged rats and 2) aged rats respond to physiological levels of rat PTH. Conscious adult (7-mo-old) and aged (25-mo-old) male Sprague-Dawley rats were infused for 2 h with rat PTH-(1-34) to achieve steady-state levels in plasma (110-120 pg/ml). Basal irPTH levels were 77% higher (P less than 0.01), and 1,25-dihydroxyvitamin D3 [1,25(OH)2D3] levels were 46% lower (P less than 0.05) in the aged rats. Renal function was not significantly different in these two groups. The metabolic clearance rate of irPTH was rapid and not different in adult and aged rats (99 +/- 8 vs. 111 +/- 7 ml.min-1.kg-1, respectively). After the PTH infusion, plasma ionized and total calcium and 1,25(OH)2D3 levels increased significantly in adult rats, whereas no changes were observed in aged rats. In contrast, a similar significant hypophosphatemic response (23-25% decrease) was seen in both age groups, but the hypophosphatemia was maintained for longer in aged rats. Thus the elevated plasma irPTH levels in aged rats are caused solely by increased secretion. Finally, there is a heterogeneity in the responses to PTH infusion in aged rats, suggesting that the aged rat skeleton, like the kidney, is PTH resistant.


1969 ◽  
Vol 114 (2) ◽  
pp. 343-350 ◽  
Author(s):  
S. H. Danovitch ◽  
L. Laster

1. Arylsulphatase activity was measured in stomach, proximal and distal third of small intestine, colon, liver and kidney of foetal and neonatal Sprague–Dawley rats and Swiss mice, with nitrocatechol sulphate as substrate. 2. The specific activity in the distal small intestine, but not in the stomach, proximal small intestine or colon, increased about fourfold between 5 and 16 days after birth in both conventional and germ-free rats. 3. No comparable increase occurred in the distal small intestine of the mouse. 4. The specific activity of acid phosphatase in the distal small intestine of the rat rose only slightly when the arylsulphatase activity increased. 5. The pH optimum and Michaelis constant of arylsulphatase activity of the distal small intestine were similar for 1-day-old, 9-day-old and adult rats. 6. When extracts of distal small intestine of 1-day-old and 9-day-old rats were incubated together, the arylsulphatase activities were additive.


1987 ◽  
Vol 253 (5) ◽  
pp. H1298-H1304
Author(s):  
R. W. Gotshall ◽  
J. C. Breay-Pilcher ◽  
B. D. Boelcskevy

Impedance cardiography (IC) has the potential to be applied to very small animals for the measurement of cardiac output (Q). To evaluate this, Q measured by impedance (ZQ) and thermal dilution (TDQ) were compared in adult Sprague-Dawley rats. Absolute values for TDQ were comparable with ZQ (e.g., 29.7 vs. 26.0 ml.min-1.100 g-1), and both equally followed the change in Q caused by hemorrhage and reinfusion of blood. IC was also evaluated in neonatal rats (1 and 7 day old). Control ZQ values were 113 ml.min-1.100 g-1 for the 1-day-old rats, and 104 ml.min-1.100 g-1 for 7-day-old rats. Both stroke volume and Q decreased with head-up tilt and increased with head-down tilt for both ages. Therefore, in the neonate, ZQ decreased appropriately with age and with preload reduction. From these results, it is concluded that IC can be utilized to evaluate cardiac function in neonatal and adult rats.


Author(s):  
G. Ilse ◽  
K. Kovacs ◽  
N. Ryan ◽  
T. Sano ◽  
L. Stefaneanu ◽  
...  

Germfree state and food restriction have been shown to increase life span and delay tumor occurrence in rats. We report here the histologic, immunocytochemical and electron microscopic findings of adenohypophyses of aging, male Lobund-Wistar rats raised at Lobund Laboratories. In our previous study, the morphologic changes in the adenohypophyses of old rats have been extensively investigated by histology, immunocytochemistry and electron microscopy. Lactotroph adenomas were frequent in Long-Evans and Sprague-Dawley rats, whereas gonadotroph adenomas were frequent in Sprague-Dawley and Wistar rats.Male Lobund-Wistar rats were divided into four groups: 1) conventional, which were raised under normal non-germfree environment and received food ad libitum; 2) germfree-food ad libitum; 3) conventional environment-food restricted and 4) germfree-food restricted. The adenohypophyses were removed from 6-month-, 18-month- and 30-month-old rats. For light microscopy, adenohypophyses were fixed in formalin and embedded in paraffin.


Author(s):  
Xiangyu Liu ◽  
Xiong Xue ◽  
Junsheng Tian ◽  
Xuemei Qin ◽  
Shi Zhou ◽  
...  

The objectives of this study were to compare the antidepressant effects between endurance and resistance exercise for optimizing interventions and examine the metabolomic changes in different types of skeletal muscles in response to the exercise, using a rat model of chronic unpredictable mild stress (CUMS)-induced depression. There were 32 male Sprague-Dawley rats randomly divided into a control group (C) and 3 experimental groups: CUMS control (D), endurance exercise (E), and resistance exercise (R). Group E underwent 30 min treadmill running, and group R performed 8 rounds of ladder climbing, 5 sessions per week for 4 weeks. Body weight, sucrose preference, and open field tests were performed pre and post the intervention period for changes in depressant symptoms, and the gastrocnemius and soleus muscles were sampled after the intervention for metabolomic analysis using the 1H-NMR technique. The results showed that both types of exercise effectively improved the depression-like symptoms, and the endurance exercise appeared to have a better effect. The levels of 10 metabolites from the gastrocnemius and 13 metabolites from the soleus of group D were found to be significantly different from that of group C, and both types of exercise had a callback effect on these metabolites, indicating that a number of metabolic pathways were involved in the depression and responded to the exercise interventions.


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

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.


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