scholarly journals Evaluation of the mitochondrial respiration of cardiac myocytes in rats submitted to mechanical bile duct obstruction

2008 ◽  
Vol 23 (suppl 1) ◽  
pp. 66-71 ◽  
Author(s):  
Rafael Kemp ◽  
Orlando de Castro-e-Silva ◽  
José Sebastião dos Santos ◽  
Ajith Kumar Sankarankutty ◽  
Rodrigo Borges Correa ◽  
...  
Keyword(s):  
Oxygen Consumption ◽  
Statistical Analysis ◽  
Bile Duct ◽  
Mitochondrial Respiration ◽  
Respiratory Control ◽  
Cellular Respiration ◽  
Sham Operation ◽  
Significant Drop ◽  
Stage 4 ◽  
Male Wistar Rats

PURPOSE: The objective of the present study was to evaluate the capacity of the myocardium for energy production by the analysis of mitochondrial respiration in rats with jaundice submitted to bile duct ligature. METHODS: Sixteen male Wistar rats were divided into 2 Groups: Group SO submitted to nontherapeutic laparotomy (sham operation) and Group IC (icteric group) submitted to bile duct ligature. After 7 days, laparotomy was again performed in all animals for cardiac muscle extraction and analysis. Mitochondrial oxygen consumption was determined by stage 3 velocity and stage 4 velocity. The respiratory control ratio (RCR) was obtained by the ratio of stage 3 to stage 4 velocity. Statistical analysis was performed by the Mann-Whitney test, with the level of significance set at 5% (p<0.05). RESULTS: Statistical analysis revealed a significant drop in oxygen consumption during stage 3 mitochondrial respiration in group IC compared with SO, whereas the values obtained during stage 4 were basically identical for the two groups. Likewise, RCR values exhibited a significant reduction. CONCLUSION: The cellular respiration of the "jaundiced heart" is depressed. This was demonstrated by the reduced capacity of cardiac mitochondria to consume oxygen and synthesize ATP, supporting the idea of a latent cardiac impairment responsible for the hemodynamic decompensation occurring during cholestasis.

scholarly journals Sepiapterin Improves Vascular Reactivity and Insulin-Stimulated Glucose in Wistar Rats

2018 ◽  
Vol 2018 ◽  
pp. 1-10 ◽  
Author(s):  
A. C. Keller ◽  
L. A. Knaub ◽  
R. L. Scalzo ◽  
S. E. Hull ◽  
A. E. Johnston ◽  
...  
Keyword(s):  
Mitochondrial Respiration ◽  
Wistar Rats ◽  
Vascular Reactivity ◽  
Disease Risk ◽  
Cardiovascular Disease Risk ◽  
Respiratory Control ◽  
Mitochondrial Activity ◽  
Insulin Tolerance ◽  
Male Wistar Rats ◽  
Endothelial Nitric Oxide

In the vasculature, sedentary behavior leads to endothelial abnormalities, resulting in elevated cardiovascular disease risk. Endothelial nitric oxide synthase (eNOS) aberrations characterize endothelial dysfunction; eNOS also regulates mitochondrial function. We hypothesized that sepiapterin (a precursor to eNOS cofactor tetrahydrobiopterin (BH4)) supplementation would improve endothelium-dependent vascular relaxation in sedentary animals via modulation of NOS function and mitochondrial activity. Sedentary male Wistar rats were fed ad libitum for a total of 10 weeks. Sepiapterin was administered in diet during the final 5 weeks. Intraperitoneal insulin and glucose tolerance tests (IP-ITT/IP-GTT) were conducted at baseline and endpoint. Aorta was assessed for vasoreactivity and mitochondrial respiration. Insulin tolerance, determined by IP-ITT, significantly improved in rats treated with sepiapterin (p<0.05, interaction of time and treatment). Acetylcholine- (ACh-) driven vasodilation was significantly greater in aorta from sepiapterin-treated rats as compared with control (76.4% versus 54.9% of phenylephrine contraction at 20 μM ACh, p<0.05). Sepiapterin treatment resulted in significantly elevated state 3 (9.00 oxygen pmol/sec∗mg versus 8.17 oxygen pmol/sec∗mg, p<0.05) and 4 (7.28 oxygen pmol/sec∗mg versus 5.86 oxygen pmol/sec∗mg, p<0.05) aortic mitochondrial respiration with significantly lower respiratory control ratio (p<0.05) during octanoylcarnitine-driven respiration. Vasodilation and insulin sensitivity were improved through targeting NOS via sepiapterin supplementation.

scholarly journals Liver histological, portal flow and plasmatic nitric oxide alterations caused by biliary obstruction and drainage in rats

2008 ◽  
Vol 23 (suppl 1) ◽  
pp. 2-7 ◽  
Author(s):  
Miguel Angel Dias ◽  
Reginaldo Ceneviva ◽  
Jorge Elias Jr. ◽  
Sergio Zucoloto ◽  
Caroline Floreoto Baldo ◽  
...  
Keyword(s):  
Bile Duct ◽  
Biliary Obstruction ◽  
Bile Duct Ligation ◽  
Sham Operation ◽  
Portal Flow ◽  
Histological Alterations ◽  
Duct Occlusion ◽  
Duct Ligation ◽  
Male Wistar Rats ◽  
Periodic Evaluation

PURPOSE: To evaluate liver alterations caused by biliary obstruction and drainage. METHODS: Thirty-nine male Wistar rats were randomly distributed in 4 groups: BO (n=18) bile duct ligation for 20 days, with a periodic evaluation of liver histological alterations, Doppler echography portal flow and measurements of NO and malondialdehyde (MDA); BO/DB (n=13) bile duct occlusion for 20 days followed by biliary drainage by choledochoduodenal anastomosis, 5 days follow-up, same BO group parameters evaluations; group CED (n=4) sham operation and portal flow evaluation trough 20 days; CHB (n=4) sham operation, with hepatic biopsy on 25th day and followed-up trough 25 days, by the same parameters of group BO, with exception of portal flow. Direct bilirubin (DB) and alkaline phosphatase (AP) were evaluated in the group BO, BO/DB and CHB. RESULTS: The bile duct ligation led to an increase of DB and AP, development of liver histological alterations, reduction of portal flow and increase of plasmatic NO and of MDA levels. The bile duct clearing resulted in a reduction of DB, AP, NO, MDA histological alterations and increase of portal flow. CONCLUSION: The biliary occlusion resulted in cholestasis and portal flow reduction, besides the increase of plasmatic NO and of hepatic MDA levels, and histological liver alterations, with a tendency of normalization after the bile duct clearing.

scholarly journals Relative sensitivity of soluble guanylate cyclase and mitochondrial respiration to endogenous nitric oxide at physiological oxygen concentration

2007 ◽  
Vol 405 (2) ◽  
pp. 223-231 ◽  
Author(s):  
Félix Rodríguez-Juárez ◽  
Enara Aguirre ◽  
Susana Cadenas
Keyword(s):  
Nitric Oxide ◽  
Oxygen Consumption ◽  
Oxygen Concentration ◽  
Guanylate Cyclase ◽  
Mitochondrial Respiration ◽  
Soluble Guanylate Cyclase ◽  
Atmospheric Oxygen ◽  
Cellular Respiration ◽  
Cell Physiology ◽  
Experimental Conditions

Nitric oxide (NO) is a widespread biological messenger that has many physiological and pathophysiological roles. Most of the physiological actions of NO are mediated through the activation of sGC (soluble guanylate cyclase) and the subsequent production of cGMP. NO also binds to the binuclear centre of COX (cytochrome c oxidase) and inhibits mitochondrial respiration in competition with oxygen and in a reversible manner. Although sGC is more sensitive to endogenous NO than COX at atmospheric oxygen tension, the more relevant question is which enzyme is more sensitive at physiological oxygen concentration. Using a system in which NO is generated inside the cells in a finely controlled manner, we determined cGMP accumulation by immunoassay and mitochondrial oxygen consumption by high-resolution respirometry at 30 μM oxygen. In the present paper, we report that the NO EC50 of sGC was approx. 2.9 nM, whereas that required to achieve IC50 of respiration was 141 nM (the basal oxygen consumption in the absence of NO was 14±0.8 pmol of O2/s per 106 cells). In accordance with this, the NO–cGMP signalling transduction pathway was activated at lower NO concentrations than the AMPKs (AMP-activated protein kinase) pathway. We conclude that sGC is approx. 50-fold more sensitive than cellular respiration to endogenous NO under our experimental conditions. The implications of these results for cell physiology are discussed.

scholarly journals Effects of sodium and potassium ions on oxidative phosphorylation in relation to respiratory control by a cell-membrane adenosine triphosphatase

1965 ◽  
Vol 97 (2) ◽  
pp. 523-531 ◽  
Author(s):  
DM Blond ◽  
R Whittam
Keyword(s):  
Oxygen Consumption ◽  
Cell Membrane ◽  
Oxidative Phosphorylation ◽  
Adenosine Triphosphatase ◽  
Respiratory Control ◽  
Enzymic Activity ◽  
Cellular Respiration ◽  
Physiological Concentration ◽  
A Cell ◽  
K Concentration

1. A study has been made of the oxygen consumption of kidney homogenates in relation to the ADP concentration as regulated by the cell-membrane adenosine triphosphatase. Stimulation of this enzymic activity by Na(+) and K(+) caused parallel increases in oxygen consumption and ADP concentration. Similarly, inhibition with ouabain caused a parallel fall. The membrane adenosine triphosphatase concerned in active transport therefore appears to regulate respiration through its control of ADP concentration. 2. The respiration of homogenates and mitochondria was also stimulated by K(+) in a way independent of adenosine-triphosphatase activity. It was shown that K(+) facilitates oxidative phosphorylation and the respiratory response to ADP. A K(+) concentration of 25-50mm was needed for maximum oxidative phosphorylation in the presence of physiological concentration of Na(+). Na(+) counteracted K(+) in the effects on mitochondria. It is concluded that K(+) regulates cellular respiration at two structures, one directly in mitochondria, and the second indirectly through control of ADP production at the cell membrane.

scholarly journals Bioenergetic characterization of mouse podocytes

2010 ◽  
Vol 299 (2) ◽  
pp. C464-C476 ◽  
Author(s):  
Yoshifusa Abe ◽  
Toru Sakairi ◽  
Hiroshi Kajiyama ◽  
Shashi Shrivastav ◽  
Craig Beeson ◽  
...  
Keyword(s):  
Oxygen Consumption ◽  
Mitochondrial Respiration ◽  
Energy Homeostasis ◽  
Atp Synthesis ◽  
Cellular Respiration ◽  
Similar Data ◽  
Primary Role ◽  
Atp Content ◽  
Mitochondrial Uncoupling ◽  
Primary Mouse

Mitochondrial dysfunction contributes to podocyte injury, but normal podocyte bioenergetics have not been characterized. We measured oxygen consumption rates (OCR) and extracellular acidification rates (ECAR), using a transformed mouse podocyte cell line and the Seahorse Bioscience XF24 Extracellular Flux Analyzer. Basal OCR and ECAR were 55.2 ± 9.9 pmol/min and 3.1 ± 1.9 milli-pH units/min, respectively. The complex V inhibitor oligomycin reduced OCR to ∼45% of baseline rates, indicating that ∼55% of cellular oxygen consumption was coupled to ATP synthesis. Rotenone, a complex I inhibitor, reduced OCR to ∼25% of the baseline rates, suggesting that mitochondrial respiration accounted for ∼75% of the total cellular respiration. Thus ∼75% of mitochondrial respiration was coupled to ATP synthesis and ∼25% was accounted for by proton leak. Carbonyl cyanide p-trifluoromethoxyphenylhydrazone (FCCP), which uncouples electron transport from ATP generation, increased OCR and ECAR to ∼360% and 840% of control levels. FCCP plus rotenone reduced ATP content by 60%, the glycolysis inhibitor 2-deoxyglucose reduced ATP by 35%, and 2-deoxyglucose in combination with FCCP or rotenone reduced ATP by >85%. The lactate dehydrogenase inhibitor oxamate and 2-deoxyglucose did not reduce ECAR, and 2-deoxyglucose had no effect on OCR, although 2-deoxyglucose reduced ATP content by 25%. Mitochondrial uncoupling induced by FCCP was associated with increased OCR with certain substrates, including lactate, glucose, pyruvate, and palmitate. Replication of these experiments in primary mouse podocytes yielded similar data. We conclude that mitochondria play the primary role in maintaining podocyte energy homeostasis, while glycolysis makes a lesser contribution.

A new method for the experimental induction of secundary biliary cirrhosis in wistar rats

2001 ◽  
Vol 16 (2) ◽  
pp. 75-81 ◽  
Author(s):  
Gracinda De Lourdes Jorge ◽  
Luiz Sergio Leonardi ◽  
Ilka de Fatima Santana Ferreira Boin ◽  
Orlando de Castro e Silva Jr ◽  
Cecilia Amelia Fazzio Escanhoela
Keyword(s):  
Bile Duct ◽  
Morphological Study ◽  
Wistar Rats ◽  
Hepatic Duct ◽  
Control Group ◽  
Sham Operation ◽  
Biliary Cirrhosis ◽  
Technical Failure ◽  
Duct Obstruction ◽  
Duct Ligation

The aim of this study was to describe a method for the induction of experimental secondary biliary fibrosis (SBF). Forty-seven Wistar rats were submitted to hepatic duct obstruction (OB group) for thirty days without ligature, section or cannulization causing interruption of biliary flow. This technique was carried out by simple traction of the bile duct passing it through the xiphoid appendix. Nine rats were submitted to a sham operation for bile duct stricture and seven rats comprised the control group. Blood samples were collected for the measurement of total bilirubin (TB), alkaline phosphatase (AP), alanine aminotransferase (ALT) and aspartate aminotransferase (AST). Liver fragments were removed for morphological study. Thirty days after surgery TB, AP, ALT and AST levels were significantly increased in the hepatic duct ligation group compared to the sham operated group and the presence of SBF in the OB group was confirmed by morphological study of the liver. There was technical failure in 31.92% cases. The survival was 100% at fifteen days and 82.97% at the end of the experiment. We concluded that this simple surgical technique may be used to study the consequence of bile duct obstruction which could be a reversible process depending on the obstruction time. This technique can be carried out from cholestasis to fibrosis.

scholarly journals Cell-Permeable Succinate Rescues Mitochondrial Respiration in Cellular Models of Statin Toxicity

2021 ◽  
Vol 22 (1) ◽  
pp. 424
Author(s):  
Vlad F. Avram ◽  
Imen Chamkha ◽  
Eleonor Åsander-Frostner ◽  
Johannes K. Ehinger ◽  
Romulus Z. Timar ◽  
...  
Keyword(s):  
Oxygen Consumption ◽  
Mitochondrial Dysfunction ◽  
Mitochondrial Respiration ◽  
Complex I ◽  
Ex Vivo ◽  
Coupling Efficiency ◽  
Human Platelets ◽  
Lipid Lowering ◽  
Lipid Lowering Therapy ◽  
Cellular Models

Statins are the cornerstone of lipid-lowering therapy. Although generally well tolerated, statin-associated muscle symptoms (SAMS) represent the main reason for treatment discontinuation. Mitochondrial dysfunction of complex I has been implicated in the pathophysiology of SAMS. The present study proposed to assess the concentration-dependent ex vivo effects of three statins on mitochondrial respiration in viable human platelets and to investigate whether a cell-permeable prodrug of succinate (complex II substrate) can compensate for statin-induced mitochondrial dysfunction. Mitochondrial respiration was assessed by high-resolution respirometry in human platelets, acutely exposed to statins in the presence/absence of the prodrug NV118. Statins concentration-dependently inhibited mitochondrial respiration in both intact and permeabilized cells. Further, statins caused an increase in non-ATP generating oxygen consumption (uncoupling), severely limiting the OXPHOS coupling efficiency, a measure of the ATP generating capacity. Cerivastatin (commercially withdrawn due to muscle toxicity) displayed a similar inhibitory capacity compared with the widely prescribed and tolerable atorvastatin, but did not elicit direct complex I inhibition. NV118 increased succinate-supported mitochondrial oxygen consumption in atorvastatin/cerivastatin-exposed platelets leading to normalization of coupled (ATP generating) respiration. The results acquired in isolated human platelets were validated in a limited set of experiments using atorvastatin in HepG2 cells, reinforcing the generalizability of the findings.

The effectiveness of early local administration of hyaluronic acid in experimental traumatic ischemia of the limb muscles

2021 ◽  
Author(s):  
A.V. Shulepov ◽  
I.A. Shperling ◽  
Yu.V. Yurkevich ◽  
N.V. Shperling
Keyword(s):  
Oxygen Consumption ◽  
Hyaluronic Acid ◽  
Oxygen Saturation ◽  
Wistar Rats ◽  
Soft Tissues ◽  
Local Administration ◽  
Compression Injury ◽  
Doppler Flowmetry ◽  
Muscle Ischemia ◽  
Male Wistar Rats

The experiments were performed on 280 male Wistar rats weighing 300-340 g. The design of the study included: modeling of compression injury of the soft tissues of the thigh, local injection of the preparation of hyaluronic acid "Gialift 3.5" into the area of damage 3 hours after the cessation of compression, taking into account the results after 7, 14 and 28 days. The introduction of hyaluronic acid into the area of compression injury of soft tissues reduces the severity of myoglobinemia, increases the immunohistochemical density of VEGF-positive cells, improves the perfusion characteristics of microcirculation, oxygen saturation, and specific oxygen consumption by tissues. Keywords: traumatic muscle ischemia, hyaluronic acid, myoglobin, microcirculation, metabolism, laser Doppler flowmetry, morphometry.

scholarly journals MiR-138 protects cardiac cells against hypoxia through modulation of glucose metabolism by targetting pyruvate dehydrogenase kinase 1

2017 ◽  
Vol 37 (6) ◽  
Author(s):  
Hang Zhu ◽  
Hao Xue ◽  
Qin-Hua Jin ◽  
Jun Guo ◽  
Yun-Dai Chen
Keyword(s):  
Pyruvate Dehydrogenase ◽  
Mitochondrial Respiration ◽  
Cardiac Cells ◽  
Pyruvate Dehydrogenase Kinase ◽  
Cellular Respiration ◽  
Small Noncoding Rnas ◽  
Direct Binding ◽  
Inhibition Of Glycolysis ◽  
Pyruvate Dehydrogenase Kinase 1 ◽  
Novel Therapeutic Strategies

Dysfunction of cardiac cells under hypoxia has been identified as an essential event leading to myocytes functional failure. MiRNAs are importantly regulatory small-noncoding RNAs that negatively regulate gene expression through the direct binding of 3′-UTR region of their target mRNAs. Recent studies have demonstrated that miRNAs are aberrantly expressed in the cardiovascular system under pathological conditions.Pyruvate dehydrogenase kinase 1 (PDK1) is a kinase which phosphorylates pyruvate dehydrogenase to inactivate it, leading to elevated anaerobic glycolysis and decreased cellular respiration. In the present study, we report that miR-138 expressions were significantly suppressed under long exposure to hypoxia. In addition, overexpression of miR-138 protects human cardiac cells against hypoxia. We observed miR-138 inhibits glycolysis but promotes mitochondrial respiration through directly targetting PDK1. Moreover, we demonstrate that hypoxia induces cardiac cell death through increased glycolysis and decreased mitochondrial respiration. Inhibition of glycolysis by either glycolysis inhibitor or knockdown glycolysis enzymes, Glucose transportor 1 (Glut1) or PDK1 contributes to cardiac cells’ survival. The cell sentivity to hypoxia was recovered when the PDK1 level was restored in miR-138 overexpressing cardiac cells. The present study leads to the intervention of novel therapeutic strategies against cardiac cells dysfunction during surgery or ischemia.

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