Metabolic alterations in proximal tubule suspensions obtained from ischemic kidneys

1989 ◽  
Vol 257 (3) ◽  
pp. F383-F389 ◽  
Author(s):  
K. M. Gaudio ◽  
G. Thulin ◽  
T. Ardito ◽  
M. Kashgarian ◽  
N. J. Siegel
Keyword(s):  
Oxygen Consumption ◽  
Proximal Tubule ◽  
Ischemic Injury ◽  
Resonance Spectroscopy ◽  
Base Line ◽  
Sprague Dawley ◽  
Significant Difference ◽  
Characteristic Features ◽  
Line Oxygen

A viable suspension of proximal tubules that had sustained an in vivo ischemic injury was harvested, and cellular integrity and viability were determined. The histopathological appearance of this preparation has characteristic features of an ischemic injury and ATP levels were comparable to those observed with nuclear magnetic resonance spectroscopy in vivo. Sprague-Dawley rats were subjected to 45 min of bilateral renal artery ischemia and the kidneys were allowed to reperfuse for either 15 min, 2 h, or 24 h before the harvest of the proximal tubule suspension. There was a decrease in base-line oxygen consumption from 34 +/- 0.8 nmol O2.min-1.mg protein-1 to 22 +/- 0.6 at 15 min of reflow. This decline in oxygen consumption persisted during the first 2 h of reflow and returned to control levels by 24 h. Residual respiration in the presence of ouabain was similar at all reflow intervals suggesting that the decrease in basal O2 consumption was related to decreased Na+-K+-ATPase in situ. In contrast, there was no significant difference in Na+-K+-ATPase activity when determined chemically under Vmax conditions in all experimental groups.(ABSTRACT TRUNCATED AT 250 WORDS)

scholarly journals Comparison of in vivo postexercise phosphocreatine recovery and resting ATP synthesis flux for the assessment of skeletal muscle mitochondrial function

2010 ◽  
Vol 299 (5) ◽  
pp. C1136-C1143 ◽  
Author(s):  
N. M. A. van den Broek ◽  
J. Ciapaite ◽  
K. Nicolay ◽  
J. J. Prompers
Keyword(s):  
Skeletal Muscle ◽  
Oxygen Consumption ◽  
Mitochondrial Dysfunction ◽  
Mitochondrial Function ◽  
Atp Synthesis ◽  
Resonance Spectroscopy ◽  
Isolated Mitochondria ◽  
Significant Difference

31P magnetic resonance spectroscopy (MRS) has been used to assess skeletal muscle mitochondrial function in vivo by measuring 1) phosphocreatine (PCr) recovery after exercise or 2) resting ATP synthesis flux with saturation transfer (ST). In this study, we compared both parameters in a rat model of mitochondrial dysfunction with the aim of establishing the most appropriate method for the assessment of in vivo muscle mitochondrial function. Mitochondrial dysfunction was induced in adult Wistar rats by daily subcutaneous injections with the complex I inhibitor diphenyleneiodonium (DPI) for 2 wk. In vivo 31P MRS measurements were supplemented by in vitro measurements of oxygen consumption in isolated mitochondria. Two weeks of DPI treatment induced mitochondrial dysfunction, as evidenced by a 20% lower maximal ADP-stimulated oxygen consumption rate in isolated mitochondria from DPI-treated rats oxidizing pyruvate plus malate. This was paralleled by a 46% decrease in in vivo oxidative capacity, determined from postexercise PCr recovery. Interestingly, no significant difference in resting, ST-based ATP synthesis flux was observed between DPI-treated rats and controls. These results show that PCr recovery after exercise has a more direct relationship with skeletal muscle mitochondrial function than the ATP synthesis flux measured with 31P ST MRS in the resting state.

scholarly journals In Vivo Measurement of Neurochemical Abnormalities in the Hippocampus in a Rat Model of Cuprizone-Induced Demyelination

Diagnostics ◽  
2020 ◽  
Vol 11 (1) ◽  
pp. 45
Author(s):  
Do-Wan Lee ◽  
Jae-Im Kwon ◽  
Chul-Woong Woo ◽  
Hwon Heo ◽  
Kyung Won Kim ◽  
...  
Keyword(s):  
Magnetic Resonance ◽  
Rat Model ◽  
Resonance Spectroscopy ◽  
Chow Diet ◽  
Gamma Aminobutyric Acid ◽  
Sprague Dawley ◽  
In Vivo Measurement ◽  
Hippocampal Lesions ◽  
Total Creatine

This study quantitatively measured the changes in metabolites in the hippocampal lesions of a rat model of cuprizone-induced demyelination as detected using in vivo 7 T proton magnetic resonance spectroscopy. Nineteen Sprague Dawley rats were randomly divided into two groups and fed a normal chow diet or cuprizone (0.2%, w/w) for 7 weeks. Demyelinated hippocampal lesions were quantitatively measured using a 7 T magnetic resonance imaging scanner. All proton spectra were quantified for metabolite concentrations and relative ratios. Compared to those in the controls, the cuprizone-induced rats had significantly higher concentrations of glutamate (p = 0.001), gamma-aminobutyric acid (p = 0.019), and glutamate + glutamine (p = 0.001); however, creatine + phosphocreatine (p = 0.006) and myo-inositol (p = 0.001) concentrations were lower. In addition, we found that the glutamine and glutamate complex/total creatine (p < 0.001), glutamate/total creatine (p < 0.001), and GABA/total creatine (p = 0.002) ratios were significantly higher in cuprizone-treated rats than in control rats. Our results showed that cuprizone-induced neuronal demyelination may influence the severe abnormal metabolism in hippocampal lesions, and these responses could be caused by microglial activation, mitochondrial dysfunction, and astrocytic necrosis.

Androgens augment proximal tubule transport

2004 ◽  
Vol 287 (3) ◽  
pp. F452-F459 ◽  
Author(s):  
Albert Quan ◽  
Sumana Chakravarty ◽  
Jian-Kang Chen ◽  
Jian-Chun Chen ◽  
Samer Loleh ◽  
...  
Keyword(s):  
Angiotensin Ii ◽  
Proximal Tubule ◽  
Specific Binding ◽  
Extracellular Volume ◽  
Renin Angiotensin System ◽  
Angiotensin Receptors ◽  
Sprague Dawley ◽  
Angiotensin System ◽  
Renin Angiotensin

The proximal tubule contains an autonomous renin-angiotensin system that regulates transport independently of circulating angiotensin II. Androgens are known to increase expression of angiotensinogen, but the effect of androgens on proximal tubule transport is unknown. In this in vivo microperfusion study, we examined the effect of androgens on proximal tubule transport. The volume reabsorptive rate in Sprague-Dawley rats given dihydrotestosterone (DHT) injections was significantly higher than in control rats given vehicle injections (4.57 ± 0.31 vs. 3.31 ± 0.23 nl·min−1·mm−1, P < 0.01). Luminally perfusing with either enalaprilat (10−4 M) to inhibit production of angiotensin II or losartan (10−8 M) to block the angiotensin receptor decreased the proximal tubule volume reabsorptive rate in DHT-treated rats to a significantly greater degree than in control vehicle-injected rats. The renal expression of angiotensinogen was shown to be higher in the DHT-treated animals, using Northern blot analysis. The expression of angiotensin receptors, determined by specific binding of angiotensin II, was not different in the two groups of animals. Brush-border membrane protein abundance of the Na/H exchanger, a membrane transport protein under angiotensin II regulation, was also higher in DHT-treated rats vs. control rats. Rats that received DHT had higher blood pressures than the control rats but had no change in their glomerular filtration rate. In addition, serum angiotensin II levels were lower in DHT-treated vs. control rats. These results suggest that androgens may directly upregulate the proximal tubule renin-angiotensin system, increase the volume reabsorptive rate, and thereby increase extracellular volume and blood pressure and secondarily decrease serum angiotensin II levels.

scholarly journals Expression and Role of Parathyroid Hormone-Related Protein in Human Renal Proximal Tubule Cells during Recovery from ATP Depletion

1999 ◽  
Vol 10 (2) ◽  
pp. 238-244
Author(s):  
ADOLFO GARCÍA-OCAÑA ◽  
SUSAN C. GALBRAITH ◽  
SCOTT K. VAN WHY ◽  
KAI YANG ◽  
LINA GOLOVYAN ◽  
...  
Keyword(s):  
Proximal Tubule ◽  
Recovery Period ◽  
Ischemic Injury ◽  
Atp Depletion ◽  
Proximal Tubule Cell ◽  
Pthrp Expression ◽  
Human Proximal Tubule Cell

Abstract. Parathyroid hormone (PTH)-related protein (PTHrP) is widely expressed in normal fetal and adult tissues and regulates growth and differentiation in a number of organ systems. Although various renal cell types produce PTHrP, and PTHrP expression in rat proximal renal tubules is upregulated in response to ischemic injury in vivo, the role of PTHrP in the kidney is unknown. To study the effects of injury on PTHrP expression and its consequences in more detail, the immortalized human proximal tubule cell line HK-2 was used in an in vitro model of ATP depletion to mimic in vivo renal ischemic injury. These cells secrete PTHrP into conditioned medium and express the type I PTH/PTHrP receptor. Treatment of confluent HK-2 cells for 2 h with substrate-free, glucose-free medium containing the mitochondrial inhibitor antimycin A (1 μM) resulted in 75% depletion of cellular ATP. After an additional 2 h in glucose-containing medium, cellular ATP levels recovered to approximately 75% of baseline levels. PTHrP mRNA levels, as measured in RNase protection assays, peaked at 2 h into the recovery period (at four times baseline expression). The increase in PTHrP mRNA expression was correlated with an increase in PTHrP protein content in HK-2 cells at 2 to 6 h into the recovery period. Heat shock protein-70 mRNA expression was not detectable under baseline conditions but likewise peaked at 2 h into the recovery period. Treatment of HK-2 cells during the recovery period after injury with an anti-PTHrP(1-36) antibody (at a dilution of 1:250) resulted in significant reductions in cell number and uptake of [3H]thymidine, compared with nonimmune serum at the same titer. Similar results were observed in uninjured HK-2 cells. It is concluded that this in vitro model of ATP depletion in a human proximal tubule cell line reproduces the pattern of gene expression previously observed in vivo in rat kidney after ischemic injury and that PTHrP plays a mitogenic role in the proliferative response after energy depletion.

scholarly journals Nicotinamide Mononucleotide Administration Prevents Experimental Diabetes-Induced Cognitive Impairment and Loss of Hippocampal Neurons

2020 ◽  
Vol 21 (11) ◽  
pp. 3756
Author(s):  
Krish Chandrasekaran ◽  
Joungil Choi ◽  
Muhammed Ikbal Arvas ◽  
Mohammad Salimian ◽  
Sujal Singh ◽  
...  
Keyword(s):  
Hippocampal Neurons ◽  
Neuronal Loss ◽  
Memory Deficits ◽  
Diabetic Rats ◽  
Resonance Spectroscopy ◽  
Gamma Aminobutyric Acid ◽  
Sprague Dawley ◽  
Protein Levels ◽  
Nicotinamide Mononucleotide

Diabetes predisposes to cognitive decline leading to dementia and is associated with decreased brain NAD+ levels. This has triggered an intense interest in boosting nicotinamide adenine dinucleotide (NAD+) levels to prevent dementia. We tested if the administration of the precursor of NAD+, nicotinamide mononucleotide (NMN), can prevent diabetes-induced memory deficits. Diabetes was induced in Sprague-Dawley rats by the administration of streptozotocin (STZ). After 3 months of diabetes, hippocampal NAD+ levels were decreased (p = 0.011). In vivo localized high-resolution proton magnetic resonance spectroscopy (MRS) of the hippocampus showed an increase in the levels of glucose (p < 0.001), glutamate (p < 0.001), gamma aminobutyric acid (p = 0.018), myo-inositol (p = 0.018), and taurine (p < 0.001) and decreased levels of N-acetyl aspartate (p = 0.002) and glutathione (p < 0.001). There was a significant decrease in hippocampal CA1 neuronal volume (p < 0.001) and neuronal number (p < 0.001) in the Diabetic rats. Diabetic rats showed hippocampal related memory deficits. Intraperitoneal NMN (100 mg/kg) was given after induction and confirmation of diabetes and was provided on alternate days for 3 months. NMN increased brain NAD+ levels, normalized the levels of glutamate, taurine, N-acetyl aspartate (NAA), and glutathione. NMN-treatment prevented the loss of CA1 neurons and rescued the memory deficits despite having no significant effect on hyperglycemic or lipidemic control. In hippocampal protein extracts from Diabetic rats, SIRT1 and PGC-1α protein levels were decreased, and acetylation of proteins increased. NMN treatment prevented the diabetes-induced decrease in both SIRT1 and PGC-1α and promoted deacetylation of proteins. Our results indicate that NMN increased brain NAD+, activated the SIRT1 pathway, preserved mitochondrial oxidative phosphorylation (OXPHOS) function, prevented neuronal loss, and preserved cognition in Diabetic rats.

Chronic heat improves mechanical and metabolic response of trained rat heart on ischemia and reperfusion

1997 ◽  
Vol 272 (5) ◽  
pp. H2085-H2094 ◽  
Author(s):  
E. Levy ◽  
Y. Hasin ◽  
G. Navon ◽  
M. Horowitz
Keyword(s):  
Oxygen Consumption ◽  
Intracellular Ph ◽  
Cardiac Mechanics ◽  
Heat Acclimation ◽  
High Energy ◽  
Rate Pressure Product ◽  
Resonance Spectroscopy ◽  
Ischemia And Reperfusion ◽  
Swimming Training ◽  
Significant Difference

Cardiac mechanics and metabolic performance were studied in isolated perfused hearts of rats subjected to a combined chronic stress of heat acclimation and swimming training (EXAC) or swimming training alone (EX). Diastolic (DP) and systolic pressures (SP), coronary flow (CF), and oxygen consumption were measured during normoperfusion (80 mmHg), and the appearance of ischemic contracture (IC), DP, and SP were measured during progressive graded ischemia, total ischemia (TI), and reperfusion insults. ATP, phosphocreatine, and intracellular pH were measured during TI and reperfusion with 31P nuclear magnetic resonance spectroscopy. During normoperfusion, SP and cardiac efficiency (derived from rate-pressure product-oxygen consumption relationships) were the highest in the 2-mo EXAC hearts (P < 0.0001). During progressive graded ischemia, the development of IC (percentage of total hearts) was similar in both EXAC and EX hearts; the only significant difference was confined to the 1- vs. 2-mo groups. The onset of IC was delayed in the EXAC hearts and, on reperfusion, recovery, particularly of DP, was significantly improved in the latter. After TI, EXAC hearts retained 30% of the ATP pool and there was a delayed decline in intracellular pH. On reperfusion, these hearts also displayed improved ATP and phosphocreatine recovery, the 2-mo EXAC heart demonstrating significantly faster high-energy phosphate salvage, improved diastolic function, and pulse pressure recovery. The data attest to the beneficial effects of heat acclimation on cardiac mechanics of trained rats during normoperfusion and cardiac protection on ischemia and reperfusion. Possibly, energy sparing, lesser acidosis, and shorter duration of IC on ischemia and improved energy salvage on reperfusion contribute synergistically to this potent beneficial effect.

scholarly journals Acute and Subchronic Toxicity Study ofEuphorbia hirtaL. Methanol Extract in Rats

2013 ◽  
Vol 2013 ◽  
pp. 1-14 ◽  
Author(s):  
Kwan Yuet Ping ◽  
Ibrahim Darah ◽  
Yeng Chen ◽  
Subramaniam Sreeramanan ◽  
Sreenivasan Sasidharan
Keyword(s):  
Body Weight ◽  
Toxicity Study ◽  
Morphological Alteration ◽  
Control Group ◽  
Sprague Dawley ◽  
Oral Toxicity ◽  
Methanolic Extracts ◽  
Sprague Dawley Rats ◽  
Significant Difference

DespiteEuphorbia hirtaL. ethnomedicinal benefits, very few studies have described the potential toxicity. The aim of the present study was to evaluate thein vivotoxicity of methanolic extracts ofE. hirta. The acute and subchronic oral toxicity ofE. hirtawas evaluated in Sprague Dawley rats. The extract at a single dose of 5000 mg/kg did not produce treatment related signs of toxicity or mortality in any of the animals tested during the 14-day observation period. Therefore, the LD 50 of this plant was estimated to be more than 5000 mg/kg. In the repeated dose 90-day oral toxicity study, the administration of 50 mg/kg, 250 mg/kg, and 1000 mg/kg/day ofE. hirtaextract per body weight revealed no significant difference (P>0.05) in food and water consumptions, body weight change, haematological and biochemical parameters, relative organ weights, and gross findings compared to the control group. Macropathology and histopathology examinations of all organs including the liver did not reveal morphological alteration. Analyses of these results with the information of signs, behaviour, and health monitoring could lead to the conclusion that the long-term oral administration ofE. hirtaextract for 90 days does not cause sub-chronic toxicity.

Portal hypertension increases vasoconstrictor responsiveness of rat aorta

1999 ◽  
Vol 96 (1) ◽  
pp. 41-47 ◽  
Author(s):  
Claire CONNOLLY ◽  
Teresa CAWLEY ◽  
P. Aiden MCCORMICK ◽  
James R. DOCHERTY
Keyword(s):  
Portal Hypertension ◽  
Wistar Rats ◽  
Rat Aorta ◽  
Maximum Response ◽  
Sprague Dawley ◽  
Portal Vein Stenosis ◽  
Sprague Dawley Rats ◽  
Significant Difference ◽  
Hepatic Portal

We have examined the effects of pre-hepatic portal hypertension on the responsiveness of aorta from Wistar and Sprague–Dawley rats. Rats were made portal hypertensive by creating a calibrated portal vein stenosis, or sham operated. In rat aorta, there was no significant difference between portal hypertensive and sham-operated animals in the contractile potency of KCl, noradrenaline or phenylephrine. In aortas from Wistar rats, the maximum response to KCl (0.71±0.12 ;g) and noradrenaline (1.00±0.17 ;g) but not phenylephrine (0.86±0.10 ;g) in portal hypertensive animals was significantly increased compared with that in sham-operated animals (0.45±0.04 ;g, 0.57±0.07 ;g, 0.71±0.05 ;g respectively). In aortas from Sprague–Dawley rats, the maximum response to KCl (1.21±0.21 ;g) and phenylephrine (1.54±0.30 ;g) but not noradrenaline (0.93±0.09 ;g) in portal hypertensive animals was significantly increased compared with that in sham-operated animals (0.59±0.09 ;g, 0.76±0.11 ;g, 1.04±0.10 ;g respectively). There was no difference between portal hypertensive and sham-operated Wistar rats in the affinity or maximum number of binding sites for [3H]prazosin to α1-adrenoceptors in cardiac ventricular membranes. It is concluded that portal hypertension tends to produce an increase rather than a decrease in the contractile response to vasoconstrictors in aorta from both Wistar and Sprague–Dawley rats. This suggests that the diminished responsiveness to vasoconstrictors reported in portal hypertensive rats in vivo is not due to a diminished responsiveness at the level of the vascular smooth muscle.

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