Effects of indomethacin on energy metabolism in rat jejunal tissue in vivo

2002 ◽  
Vol 102 (5) ◽  
pp. 541-546 ◽  
Author(s):  
Molly JACOB ◽  
Ingvar BJARNASON ◽  
Robert J. SIMPSON
Keyword(s):  
Energy Metabolism ◽  
Oxygen Uptake ◽  
Mitochondrial Function ◽  
Clinical Medicine ◽  
Ex Vivo ◽  
Energy Charge ◽  
Early Event ◽  
Sprague Dawley ◽  
Lactate Levels

The non-steroidal anti-inflammatory drugs (NSAIDs) are a widely used group of drugs in clinical medicine. However, their propensity to cause gastrointestinal damage limits their clinical utility. The pathogenesis of this toxicity is not well established. It has been postulated that an early event in the development of damage is an effect of these drugs on mitochondrial function. The present paper sets out to evaluate the effects of indomethacin, a commonly used NSAID, on energy metabolism in vivo. Indomethacin was administered to male Sprague-Dawley rats, either intrajejunally or orally, and indices of mitochondrial function were determined. The parameters chosen for this purpose were oxygen uptake by, lactate levels in and the energy charge of jejunal tissue. Oxygen uptake by and energy charge in jejunal tissue were unaffected at 1 and 3h after dosing by gavage with indomethacin. The drug significantly affected the tissue lactate/pyruvate ratio at 3h (but not at 1h) after oral dosing. Effects of indomethacin on jejunum incubated ex vivo were found to be reversible. The data suggest that indomethacin affects mitochondrial function in vivo, but that compensatory changes in glycolytic rate maintain energy charge.

In Vivo and ex Vivo Approaches to Studying the Biomechanical Properties of Healing Wounds in Rat Skin

2013 ◽  
Vol 135 (10) ◽  
Author(s):  
Clare Y. L. Chao ◽  
Gabriel Y. F. Ng ◽  
Kwok-Kuen Cheung ◽  
Yong-Ping Zheng ◽  
Li-Ke Wang ◽  
...  
Keyword(s):  
Wound Healing ◽  
Ex Vivo ◽  
Normal Skin ◽  
Biomechanical Properties ◽  
Skin Wound ◽  
Sprague Dawley ◽  
Rat Skin ◽  
Mechanical Stiffness ◽  
Air Jet

An evaluation of wound mechanics is crucial in reflecting the wound healing status. The present study examined the biomechanical properties of healing rat skin wounds in vivo and ex vivo. Thirty male Sprague-Dawley rats, each with a 6 mm full-thickness circular punch biopsied wound at both posterior hind limbs were used. The mechanical stiffness at both the central and margins of the wound was measured repeatedly in five rats over the same wound sites to monitor the longitudinal changes over time of before wounding, and on days 0, 3, 7, 10, 14, and 21 after wounding in vivo by using an optical coherence tomography-based air-jet indentation system. Five rats were euthanized at each time point, and the biomechanical properties of the wound tissues were assessed ex vivo using a tensiometer. At the central wound bed region, the stiffness measured by the air-jet system increased significantly from day 0 (17.2%), peaked at day 7 (208.3%), and then decreased progressively until day 21 (40.2%) as compared with baseline prewounding status. The biomechanical parameters of the skin wound samples measured by the tensiometer showed a marked reduction upon wounding, then increased with time (all p < 0.05). On day 21, the ultimate tensile strength of the skin wound tissue approached 50% of the normal skin; while the stiffness of tissue recovered at a faster rate, reaching 97% of its prewounded state. Our results suggested that it took less time for healing wound tissues to recover their stiffness than their maximal strength in rat skin. The stiffness of wound tissues measured by air-jet could be an indicator for monitoring wound healing and contraction.

scholarly journals Studies to Elucidate the Mechanism of Cardio Protective and Hypotensive Activities of Anogeissus acuminata (Roxb. ex DC.) in Rodents

Molecules ◽  
2020 ◽  
Vol 25 (15) ◽  
pp. 3471
Author(s):  
Fatima Saqib ◽  
Muhammad Arif Aslam ◽  
Khizra Mujahid ◽  
Luigi Marceanu ◽  
Marius Moga ◽  
...  
Keyword(s):  
Creatine Kinase ◽  
Ex Vivo ◽  
Inflammatory Cells ◽  
Left Ventricular ◽  
Guanosine Monophosphate ◽  
Sprague Dawley ◽  
Positive Effects ◽  
Creatine Kinase Mb

Anogeissus acuminata (Roxb. ex DC.) is a folkloric medicinal plant in Asia; including Pakistan; used as a traditional remedy for cardiovascular disorders. This study was planned to establish a pharmacological basis for the trivial uses of Anogeissus acuminata in certain medical conditions related to cardiovascular systems and to explore the underlying mechanisms. Mechanistic studies suggested that crude extract of Anogeissus acuminata (Aa.Cr) produced in vitro cardio-relaxant and vasorelaxant effects in isolated paired atria and aorta coupled with in vivo decrease in blood pressure by invasive method; using pressure and force transducers connected to Power Lab Data Acquisition System. Moreover; Aa.Cr showed positive effects in left ventricular hypertrophy in Sprague Dawley rats observed hemodynamically by a decrease in cardiac cell size and fibrosis; along with absence of inflammatory cells; coupled with reduced levels of angiotensin converting enzyme (ACE) and renin concentration along with increased concentrations of nitric oxide (NO) and cyclic guanosine monophosphate (cGMP). In Acute Myocardial Infarction (AMI) model; creatine kinase (CK), creatine kinase-MB (CK-MB) and lactic acid dehydrogenase (LDH levels) were found to be decreased; along with decreased necrosis; edema and recruitment of inflammatory cells histologically. In vivo and ex vivo studies of Anogeissus acuminata provided evidence of vasorelaxant; hypotensive and cardioprotective properties facilitated through blockage of voltage-gated Ca++ ion channel; validating its use in cardiovascular diseases

Interferon-beta affects mitochondrial activity in CD4+lymphocytes: Implications for mechanism of action in multiple sclerosis

2014 ◽  
Vol 21 (10) ◽  
pp. 1262-1270 ◽  
Author(s):  
Aiden Haghikia ◽  
Simon Faissner ◽  
Derek Pappas ◽  
Bartosz Pula ◽  
Denis A Akkad ◽  
...  
Keyword(s):  
Multiple Sclerosis ◽  
T Cells ◽  
Energy Metabolism ◽  
Mitochondrial Function ◽  
Interferon Beta ◽  
Mononuclear Cells ◽  
Ex Vivo ◽  
Mitochondrial Activity ◽  
Mitochondrial Energy Metabolism ◽  
The Impact

Background:Whereas cellular immune function depends on energy supply and mitochondrial function, little is known on the impact of immunotherapies on cellular energy metabolism.Objective:The objective of this paper is to assess the effects of interferon-beta (IFN-β) on mitochondrial function of CD4+T cells.Methods:Intracellular adenosine triphosphate (iATP) in phytohemagglutinin (PHA)-stimulated CD4+cells of multiple sclerosis (MS) patients treated with IFN-β and controls were analyzed in a luciferase-based assay. Mitochondrial-transmembrane potential (ΔΨm) in IFN-β-treated peripheral blood mononuclear cells (PBMCs) was investigated by flow cytometry. Expression of genes involved in mitochondrial oxidative phosphorylation (OXPHOS) in CD4+cells of IFN-β-treated individuals and correlations between genetic variants in the key metabolism regulator PGC-1α and IFN-β response in MS were analyzed.Results:IFN-β-treated MS patients exhibited a dose-dependent reduction of iATP levels in CD4+T cells compared to controls ( p < 0.001). Mitochondrial effects were reflected by depolarization of ΔΨm. Expression data revealed changes in the transcription of OXPHOS-genes. iATP levels in IFN-β-responders were reduced compared to non-responders ( p < 0.05), and the major T allele of the SNP rs7665116 of PGC-1α correlated with iATP-levels.Conclusion:Reduced iATP-synthesis ex vivo and differential expression of OXPHOS-genes in CD4+T cells point to unknown IFN-β effects on mitochondrial energy metabolism, adding to potential pleiotropic mechanisms of action.

scholarly journals Therapeutic Effects of Water Soluble Danshen Extracts on Atherosclerosis

2013 ◽  
Vol 2013 ◽  
pp. 1-11 ◽  
Author(s):  
Yoon Hee Cho ◽  
Cheol Ryong Ku ◽  
Zhen-Yu Hong ◽  
Ji Hoe Heo ◽  
Eun Hee Kim ◽  
...  
Keyword(s):  
Endothelial Cells ◽  
Platelet Aggregation ◽  
Ex Vivo ◽  
Umbilical Vein ◽  
Water Soluble ◽  
Therapeutic Effects ◽  
Sprague Dawley ◽  
Tail Vein ◽  
Vein Thrombosis

Danshen is a traditional Chinese medicine with many beneficial effects on cardiovascular diseases. The aim of this study was to evaluate the mechanisms responsible for the antiatherogenic effect of water soluble Danshen extracts (DEs). Rat vascular smooth muscle cells (VSMCs) and human umbilical vein endothelial cells (HUVECs) were treated with DE. To evaluate the effects of DEin vivo, carotid balloon injury and tail vein thrombosis were induced in Sprague-Dawley (SD) rats and iliac artery stent was induced in New Zealand white rabbits. The inhibitory action of DE on platelet aggregation was confirmed with an impedance aggregometer. DE inhibited the production of reactive oxygen species, and the migration and proliferation of platelet-derived growth factor-BB stimulated VSMCs. Furthermore, DE prevented inflammation and apoptosis in HUVECs. Both effects of DE were reconfirmed in both rat models. DE treatment attenuated platelet aggregation in bothin vivoandex vivoconditions. Pretreatment with DE prevented tail vein thrombosis, which is normally induced byκ-carrageenan injection. Lastly, DE-treated rabbits showed decreased in-stent restenosis of stented iliac arteries. These results suggest that water soluble DE modulates key atherogenic events in VSMCs, endothelial cells, and platelets in bothin vitroandin vivoconditions.

Contribution of whole blood to the control of plasma asymmetrical dimethylarginine

2006 ◽  
Vol 291 (4) ◽  
pp. H1788-H1796 ◽  
Author(s):  
Scott S. Billecke ◽  
Laura A. Kitzmiller ◽  
Joseph J. Northrup ◽  
Steven E. Whitesall ◽  
Masumi Kimoto ◽  
...  
Keyword(s):  
Whole Blood ◽  
Ex Vivo ◽  
Dominant Role ◽  
Peptide Bond ◽  
Sprague Dawley ◽  
Asymmetrical Dimethylarginine ◽  
Sprague Dawley Rats ◽  
Endogenous Nitric Oxide ◽  
Nos Inhibitor

The endogenous nitric oxide (NO) synthase (NOS) inhibitor asymmetrical dimethylarginine (ADMA) is elevated in many patients and may contribute to the initiation and progression of their disease. While some mechanistic pathways have been identified, tissue-specific contributions to ADMA control remain unclear. We sought to determine if whole blood (WB) could participate in ADMA control ex vivo. Anesthetized male Sprague-Dawley rats underwent exsanguinations, and WB preparations were incubated at 37°C for 5 h. ADMA and symmetrical dimethylarginine were analyzed by high-pressure liquid chromatography. Incubation of lysed red blood cell (RBC) supernatant yielded a significant decrease in ADMA that was blocked by 4124W, a synthetic inhibitor of dimethylarginine dimethylaminohydrolase, the only reported enzyme to hydrolyze ADMA. Hydrolysis of ADMA was diminished by addition of physiologically relevant concentrations of zinc (i.e., 20 μM). Conversely, when rat WB or WB supernatant was incubated at 37°C, it liberated quantities of free ADMA (1–2 μM) that in vivo would likely have pathological consequences. Addition of arginine methyltransferase inhibitors to these incubations did not reduce ADMA release, indicating no dominant role for active protein methylation during these incubations. This ADMA liberation was significantly reduced by addition of protease inhibitors, indicating a dependence on peptide bond hydrolysis. Total ADMA (protein incorporated plus free) was determined by acid hydrolysis and found to be 43.18 ± 4.79 μM in WB with ∼95% of this in RBCs. These ex vivo data demonstrate the potential of blood to control the NO-NOS system by modulating free ADMA.

Adipogenic and lipolytic effects of chronic glucocorticoid exposure

2011 ◽  
Vol 300 (1) ◽  
pp. C198-C209 ◽  
Author(s):  
Jonathan E. Campbell ◽  
Ashley J. Peckett ◽  
Anna M. D'souza ◽  
Thomas J. Hawke ◽  
Michael C. Riddell
Keyword(s):  
Adipose Tissue ◽  
Ex Vivo ◽  
Residual Effect ◽  
Hormone Sensitive Lipase ◽  
Maximum Effect ◽  
Dependent Manner ◽  
Sprague Dawley ◽  
Preadipocyte Differentiation ◽  
Concentration Dependent Manner

Glucocorticoids have been proposed to be both adipogenic and lipolytic in action within adipose tissue, although it is unknown whether these actions can occur simultaneously. Here we investigate both the in vitro and in vivo effects of corticosterone (Cort) on adipose tissue metabolism. Cort increased 3T3-L1 preadipocyte differentiation in a concentration-dependent manner, but did not increase lipogenesis in adipocytes. Cort increased lipolysis within adipocytes in a concentration-dependent manner (maximum effect at 1–10 μM). Surprisingly, removal of Cort further increased lipolytic rates (∼320% above control, P < 0.05), indicating a residual effect on basal lipolysis. mRNA and protein expression of adipose triglyceride lipase and phosphorylated status of hormone sensitive lipase (Ser563/Ser660) were increased with 48 h of Cort treatment. To test these responses in vivo, Sprague-Dawley rats were subcutaneously implanted with wax pellets with/without Cort (300 mg). After 10 days, adipose depots were removed and cultured ex vivo. Both free fatty acids and glycerol concentrations were elevated in fed and fasting conditions in Cort-treated rats. Despite increased lipolysis, Cort rats had more visceral adiposity than sham rats (10.2 vs. 6.9 g/kg body wt, P < 0.05). Visceral adipocytes from Cort rats were smaller and more numerous than those in sham rats, suggesting that adipogenesis occurred through preadipocyte differentiation rather than adipocyte hypertrophy. Visceral, but not subcutaneous, adipocyte cultures from Cort-treated rats displayed a 1.5-fold increase in basal lipolytic rates compared with sham rats ( P < 0.05). Taken together, our findings demonstrate that chronic glucocorticoid exposure stimulates both lipolysis and adipogenesis in visceral adipose tissue but favors adipogenesis primarily through preadipocyte differentiation.

scholarly journals Protective Effect of Qiliqiangxin Capsule on Energy Metabolism and Myocardial Mitochondria in Pressure Overload Heart Failure Rats

2013 ◽  
Vol 2013 ◽  
pp. 1-9 ◽  
Author(s):  
Junfang Zhang ◽  
Cong Wei ◽  
Hongtao Wang ◽  
Siwen Tang ◽  
Zhenhua Jia ◽  
...  
Keyword(s):  
Heart Failure ◽  
Energy Metabolism ◽  
Mitochondrial Function ◽  
Pressure Overload ◽  
Metabolic Intermediate ◽  
Substrate Metabolism ◽  
Myocardial Mitochondria ◽  
Tcm Theory

Qiliqiangxin capsule (QL) was developed under the guidance of TCM theory of collateral disease and had been shown to be effective and safe for the treatment of heart failure. The present study explored the role of and mechanism by which the herbal compounds QL act on energy metabolism,in vivo, in pressure overload heart failure. SD rats received ascending aorta constriction (TAC) to establish a model of myocardial hypertrophy. The animals were treated orally for a period of six weeks. QL significantly inhibited cardiac hypertrophy due to ascending aortic constriction and improved hemodynamics. This effect was linked to the expression levels of the signaling factors in connection with upregulated energy and the regulation of glucose and lipid substrate metabolism and with a decrease in metabolic intermediate products and the protection of mitochondrial function. It is concluded that QL may regulate the glycolipid substrate metabolism by activating AMPK/PGC-1αaxis and reduce the accumulation of free fatty acids and lactic acid, to protect cardiac myocytes and mitochondrial function.

Graded occlusion of perfused rat muscle vasculature decreases insulin action

2007 ◽  
Vol 112 (8) ◽  
pp. 457-466 ◽  
Author(s):  
Georgie C. Vollus ◽  
Eloise A. Bradley ◽  
Merren K. Roberts ◽  
John M. B. Newman ◽  
Stephen M. Richards ◽  
...  
Keyword(s):  
Oxygen Uptake ◽  
Glucose Uptake ◽  
Insulin Action ◽  
Energy Charge ◽  
Dry Weight ◽  
Capillary Recruitment ◽  
Akt Phosphorylation ◽  
Rat Muscle ◽  
Hindlimb Muscle

Insulin increases capillary recruitment in vivo and impairment of this may contribute to muscle insulin resistance by limiting either insulin or glucose delivery. In the present study, the effect of progressively decreased rat muscle perfusion on insulin action using graded occlusion with MS (microspheres; 15 μm in diameter) was examined. EC (energy charge), PCr/Cr (phosphocreatine/creatine ratio), AMPK (AMP-activated protein kinase) phosphorylation on Thr172 (P-AMPKα/total AMPK), oxygen uptake, nutritive capacity, 2-deoxyglucose uptake, Akt phosphorylation on Ser473 (P-Akt/total Akt) and muscle 2-deoxyglucose uptake were determined. Arterial injection of MS (0, 9, 15 and 30×106 MS/15 g of hindlimb muscle, as a bolus) into the pump-perfused (0.5 ml·min−1·g−1 of wet weight) rat hindlimb led to increased pressure (−0.5±0.8, 15.9±2.1, 28.7±4.6 and 60.3±9.4 mmHg respectively) with minimal changes in oxygen uptake. Nutritive capacity was decreased from 10.6±1.0 to 3.8±0.9 μmol·g−1 of muscle·h−1 (P<0.05) with 30×106 MS. EC was unchanged, but PCr/Cr was decreased dose-dependently to 61% of basal with 30×106 MS. Insulin-mediated increases in P-Akt/total Akt decreased from 2.15±0.35 to 1.41±0.23 (P<0.05) and muscle 2-deoxyglucose uptake decreased from 130±19 to 80±12 μg·min−1·g−1 of dry weight (P<0.05) with 15×106 MS; basal P-AMPKα in the absence of insulin was increased, but basal P-Akt/total Akt and muscle 2-deoxyglucose uptake were unaffected. In conclusion, partial occlusion of the hindlimb muscle has no effect on basal glucose uptake and marginally impacts on oxygen uptake, but markedly impairs insulin delivery to muscle and, thus, insulin-mediated Akt phosphorylation and glucose uptake.

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