The Experts below are selected from a list of 258 Experts worldwide ranked by ideXlab platform
Wolfgang Dekant - One of the best experts on this subject based on the ideXlab platform.
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Biosynthesis of toxic glutathione conjugates from halogenated alkenes.
Toxicology Letters, 2003Co-Authors: Wolfgang DekantAbstract:Abstract Glutathione conjugation has been identified as an important detoxication reaction. However, several glutathione-dependent bioactivation reactions have been identified. Current knowledge on the mechanisms and the possible biological importance of these reactions is discussed in this article. Several polychlorinated alkenes are bioactivated in a complex, glutathione-dependent pathway. The first step is hepatic glutathione S-conjugate formation followed by cleavage to the corresponding cysteine S-conjugates, and, after translocation to the Kidney, Metabolism by renal cysteine conjugate β-lyase. β-Lyase-dependent Metabolism of halovinyl cysteine S-conjugates yields electrophilic thioketenes, whose covalent binding to cellular macromolecules is likely responsible for the observed nephrotoxicity of the parent compounds.
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Biosynthesis of toxic glutathione conjugates from halogenated alkenes.
Toxicology letters, 2003Co-Authors: Wolfgang DekantAbstract:Glutathione conjugation has been identified as an important detoxication reaction. However, several glutathione-dependent bioactivation reactions have been identified. Current knowledge on the mechanisms and the possible biological importance of these reactions is discussed in this article. Several polychlorinated alkenes are bioactivated in a complex, glutathione-dependent pathway. The first step is hepatic glutathione S-conjugate formation followed by cleavage to the corresponding cysteine S-conjugates, and, after translocation to the Kidney, Metabolism by renal cysteine conjugate beta-lyase. Beta-lyase-dependent Metabolism of halovinyl cysteine S-conjugates yields electrophilic thioketenes, whose covalent binding to cellular macromolecules is likely responsible for the observed nephrotoxicity of the parent compounds.
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chemical induced nephrotoxicity mediated by glutathione s conjugate formation
Toxicology Letters, 2001Co-Authors: Wolfgang DekantAbstract:Glutathione conjugation has been identified as an important detoxication reaction. However, several glutathione-dependent bioactivation reactions have been identified. Current knowledge on the mechanisms and the possible biological importance of these reactions is discussed in this article. Vicinal dihaloalkanes are transformed by glutathione S-transferase-catalyzed reactions to mutagenic and nephrotoxic S-(2-haloethyl) glutathione S-conjugates. Electrophilic episulphonium ions are the ultimate reactive intermediates formed and interact with nucleic acids. Several polychlorinated alkenes are bioactivated in a complex, glutathione-dependent pathway. The first step is hepatic glutathione S-conjugate formation followed by cleavage to the corresponding cysteine S-conjugates, and, after translocation to the Kidney, Metabolism by renal cystein conjugate β-lyase. β-Lyase-dependent Metabolism of halovinyl cysteine S-conjugates yields electrophilic thioketenes, whose covalent binding to cellular macromolecules is likely to be responsible for the observed nephrotoxicity of the parent compounds. Finally, hepatic glutathione conjugate formation with hydroquinones and aminophenols yields conjugates that are directed to γ-glutamyltransferase-rich tissues, such as the Kidney, where they cause alkylation or redox cycling reactions, or both, that cause organ-selective damage.
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Chemical-induced nephrotoxicity mediated by glutathione S-conjugate formation.
Toxicology letters, 2001Co-Authors: Wolfgang DekantAbstract:Glutathione conjugation has been identified as an important detoxication reaction. However, several glutathione-dependent bioactivation reactions have been identified. Current knowledge on the mechanisms and the possible biological importance of these reactions is discussed in this article. Vicinal dihaloalkanes are transformed by glutathione S-transferase-catalyzed reactions to mutagenic and nephrotoxic S-(2-haloethyl) glutathione S-conjugates. Electrophilic episulphonium ions are the ultimate reactive intermediates formed and interact with nucleic acids. Several polychlorinated alkenes are bioactivated in a complex, glutathione-dependent pathway. The first step is hepatic glutathione S-conjugate formation followed by cleavage to the corresponding cysteine S-conjugates, and, after translocation to the Kidney, Metabolism by renal cystein conjugate beta-lyase. Beta-Lyase-dependent Metabolism of halovinyl cysteine S-conjugates yields electrophilic thioketenes, whose covalent binding to cellular macromolecules is likely to be responsible for the observed nephrotoxicity of the parent compounds. Finally, hepatic glutathione conjugate formation with hydroquinones and aminophenols yields conjugates that are directed to gamma-glutamyltransferase-rich tissues, such as the Kidney, where they cause alkylation or redox cycling reactions, or both, that cause organ-selective damage.
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Biosynthesis and Cellular Effects of Toxic Glutathione S -Conjugates
Advances in experimental medicine and biology, 1996Co-Authors: Wolfgang DekantAbstract:Glutathione conjugation has been identified as an important detoxication reaction. However, several glutathione-dependent bioactivation reactions have been identified. Current knowledge on the mechanisms and the possible biological importance of these reactions is discussed in this article. Dichloromethane is metabolized by glutathione conjugation to formaldehyde via S-(chloromethyl)glutathione. Both compounds are reactive intermediates and may be responsible for the dichloromethane-induced tumorigenesis in sensitive species. Vicinal dihaloalkanes are transformed by glutathione S-transferase-catalyzed reactions to mutagenic and nephrotoxic S-(2-haloethyl)glutathione S-conjugates. Electrophilic episulphonium ions are the ultimate reactive intermediates formed and interact with nucleic acids. Several polychlorinated alkenes are bioactivated in a complex, glutathione-dependent pathway. The first step is hepatic glutathione S-conjugate formation followed by cleavage to the corresponding cysteine S-conjugates, and, after translocation to the Kidney, Metabolism by renal cystein conjugate β-lyase. β-Lyase-dependent Metabolism of halovinyl cysteine S-conjugates yields electrophilic thioketenes, whose covalent binding to cellular macromolecules is likely responsible for the observed nephrotoxicity of the parent compounds. Finally, hepatic glutathione conjugate formation with hydroquinones and aminophenols yields conjugates that are directed to γ-glutamyltransferase-rich tissues, such as the Kidney, where they undergo alkylation or redox cycling reactions, or both, that cause organ-selective damage.
Fredrik Palm - One of the best experts on this subject based on the ideXlab platform.
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Acute renal metabolic effect of metformin assessed with hyperpolarised MRI in rats
Diabetologia, 2018Co-Authors: Per M. Nielsen, Fredrik Palm, Marie Schroeder, Lotte B. Bertelsen, Christoffer LaustsenAbstract:Aims/hypothesis Metformin inhibits hepatic mitochondrial glycerol phosphate dehydrogenase, thereby increasing cytosolic lactate and suppressing gluconeogenesis flux in the liver. This inhibition alters cytosolic and mitochondrial reduction–oxidation (redox) potential, which has been reported to protect organ function in several disease states including diabetes. In this study, we investigated the acute metabolic and functional changes induced by metformin in the Kidneys of both healthy and insulinopenic Wistar rats used as a model of diabetes. Methods Diabetes was induced by intravenous injection of streptozotocin, and Kidney Metabolism in healthy and diabetic animals was investigated 4 weeks thereafter using hyperpolarised ^13C-MRI, Clark-type electrodes and biochemical analysis. Results Metformin increased renal blood flow, but did not change total Kidney oxygen consumption. In healthy rat Kidneys, metformin increased [1-^13C]lactate production and reduced mitochondrial [1-^13C]pyruvate oxidation (decreased the ^13C-bicarbonate/[1-^13C]pyruvate ratio) within 30 min of administration. Corresponding alterations to indices of mitochondrial, cytosolic and whole-cell redox potential were observed. Pyruvate oxidation was maintained in the diabetic rats, suggesting that the diabetic state abrogates metabolic reprogramming caused by metformin. Conclusions/interpretation This study demonstrates that metformin-induced acute metabolic alterations in healthy Kidneys favoured anaerobic Metabolism at the expense of aerobic Metabolism. The results suggest that metformin directly alters the renal redox state, with elevated renal cytosolic redox states as well as decreased mitochondrial redox state. These findings suggest redox biology as a novel target to eliminate the renal complications associated with metformin treatment in individuals with impaired renal function.
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Increased Kidney Metabolism as a Pathway to Kidney Tissue Hypoxia and Damage: Effects of Triiodothyronine and Dinitrophenol in Normoglycemic Rats
Advances in experimental medicine and biology, 2013Co-Authors: Malou Friederich-persson, Patrik Persson, Angelica Fasching, Peter Hansell, Lina Nordquist, Fredrik PalmAbstract:Intrarenal tissue hypoxia is an acknowledged common pathway to end-stage renal disease in clinically common conditions associated with development of chronic Kidney disease, such as diabetes and hypertension. In diabetic Kidneys, increased oxygen Metabolism mediated by mitochondrial uncoupling results in decreased Kidney oxygen tension (PO2) and contributes to the development of diabetic nephropathy. The present study investigated whether increased intrarenal oxygen Metabolism per se can cause intrarenal tissue hypoxia and Kidney damage, independently of confounding factors such as hyperglycemia and oxidative stress. Male Sprague-Dawley rats were untreated or treated with either triiodothyronine (T3, 10 g/kg bw/day, subcutaneously for 10 days) or the mitochondria uncoupler dinitrophenol (DNP, 30 mg/kg bw/day, oral gavage for 14 days), after which in vivo Kidney function was evaluated in terms of glomerular filtration rate (GFR, inulin clearance), renal blood flow (RBF, Transonic, PAH clearance), cortical PO2 (Clark-type electrodes), Kidney oxygen consumption (QO2), and proteinuria. Administration of both T3 and DNP increased Kidney QO2 and decreased PO2 which resulted in proteinuria. However, GFR and RBF were unaltered by either treatment. The present study demonstrates that increased Kidney Metabolism per se can cause intrarenal tissue hypoxia which results in proteinuria. Increased Kidney QO2 and concomitantly reduced PO2 may therefore be a mechanism for the development of chronic Kidney disease and progression to end-stage renal disease.
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determinants of Kidney oxygen consumption and their relationship to tissue oxygen tension in diabetes and hypertension
Clinical and Experimental Pharmacology and Physiology, 2013Co-Authors: Peter Hansell, Fredrik Palm, William J Welch, Roland C BlantzAbstract:The high renal oxygen (O2) demand is associated primarily with tubular O2 consumption (Qo2) necessary for solute reabsorption. Increasing O2 delivery relative to demand via increased blood flow results in augmented tubular electrolyte load following elevated glomerular filtration, which, in turn, increases metabolic demand. Consequently, elevated Kidney Metabolism results in decreased tissue oxygen tension. The metabolic efficiency for solute transport (Qo2/TNa) varies not only between different nephron sites, but also under different conditions of fluid homeostasis and disease. Contributing mechanisms include the presence of different Na+ transporters, different levels of oxidative stress and segmental tubular dysfunction. Sustained hyperglycaemia results in increased Kidney Qo2, partly due to mitochondrial dysfunction and reduced electrolyte transport efficiency. This results in intrarenal tissue hypoxia because the increased Qo2 is not matched by a similar increase in O2 delivery. Hypertension leads to renal hypoxia, mediated by increased angiotensin receptor tonus and oxidative stress. Reduced uptake in the proximal tubule increases load to the thick ascending limb. There, the increased load is reabsorbed, but at greater O2 cost. The combination of hypertension, angiotensin II and oxidative stress initiates events leading to renal damage and reduced function. Tissue hypoxia is now recognized as a unifying pathway to chronic Kidney disease. We have gained good knowledge about major changes in O2 Metabolism occurring in diabetic and hypertensive Kidneys. However, further efforts are needed to elucidate how these alterations can be prevented or reversed before translation into clinical practice.
G. Rozas - One of the best experts on this subject based on the ideXlab platform.
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Carbohydrate Metabolism in several tissues of rainbow trout, Oncorhynchus mykiss, is modified during ovarian recrudescence
Comparative Biochemistry and Physiology Part B: Comparative Biochemistry, 1993Co-Authors: P. Barciela, José L. Soengas, P. Rey, Manuel Aldegunde, G. RozasAbstract:Abstract 1. 1. Several pathways of carbohydrate Metabolism were evaluated in three different tissues—liver, gonad and Kidney—of a hatchery-reared population of rainbow trout ( Oncorhynchus mykiss ) which characterised two different stages of their gonadal maturation, i.e. previtellogenesis and established exogenous vitellogenesis. 2. 2. A fall in liver glycogen levels was observed during exogenous vitellogenesis. A decrease in activity of the enzymes involved in glycolysis and in the pentose phosphate shunt was also observed, suggesting that at the end of exogenous vitellogenesis the necessity of energy and reducing power has decreased compared to the situation at the onset of this period. 3. 3. The main changes observed in gonad during vitellogenesis were the decreased activity of glycolysis and the pentose phosphate shunt as well as increased glycogen levels. The stored glycogen should be used later in association with the embryo development. 4. 4. No major changes were observed in Kidney Metabolism throughout the vitellogenic process. 5. 5. Exogenous vitellogenesis in rainbow trout is mainly associated with increased glycogen levels in the gonad and decreased metabolic activity in the liver.
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Changes in carbohydrate Metabolism related to the onset of ovarian recrudescence in dmesticated rainbow trout (Oncorhynchus mykiss)
Comparative Biochemistry and Physiology Part A: Physiology, 1993Co-Authors: José L. Soengas, P. Barciela, Manuel Aldegunde, B. Sanmartín, G. RozasAbstract:Abstract 1. 1. A study of several carbohydrate Metabolism pathways was carried out in three different tissues—liver, gonad and Kidney—from domesticated female rainbow trout ( Oncorhynchus mykiss ) at three different stages ofgonadal maturation, i.e. previtellogenesis, endogenous vitellogenesis and the onset of exogenous vitellogenesis. 2. 2. A fall in liver glycogen levels was observed at the beginning of gonadal recrudescence. The glucose obtained by glycogen rupture appears to be used both in liver glycolysis and in generating reducing power. In addition, a decrease in both the use of exogenous glucose and gluconeogenesis was also observed. 3. 3. A large increase in gonad glucose levels was observed at the beginning of gonadal recrudescence. This increase may be due to both a higher use of exogenous glucose (from diet and other tissues) and an increased gluconeogenesis. The higher glucose levels appear to be used not only in glycogen synthesis, but also in producing reducing power. 4. 4. No changes were observed in Kidney Metabolism that could be related to the initial stages ofgonadal maturation. 5. 5. The onset of the gonadal recrudescence in female rainbow trout is mainly associated with a higher use of glucose in the gonad and increased metabolic activity in the liver.
Peter F Mount - One of the best experts on this subject based on the ideXlab platform.
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increased expression and phosphorylation of 6 phosphofructo 2 kinase fructose 2 6 bisphosphatase isoforms in urinary exosomes in pre eclampsia
Journal of Translational Medicine, 2019Co-Authors: R Ellis, Marina Katerelos, Suetwan Choy, Natasha Cook, Mardiana Lee, Kathy Paizis, Gabrielle Pell, Sue Walker, David A Power, Peter F MountAbstract:Background Glycolysis is altered in various Kidney diseases, but little is known about glycolysis in pre-eclampsia, a multi-system disorder with major pathological effects on the Kidney. Urinary exosomes provide a non-invasive alternative for studying changes in Kidney Metabolism. This study aims to characterise the expression and phosphorylation of isozymes of the key glycolytic regulatory protein, 6-phosphofructokinase-2-kinase/fructose-2,6-bisphosphatase (PFK-2/FBPase-2), in urinary exosomes of subjects with pre-eclampsia (PE), compared to normotensive non-pregnant (NC) and normotensive pregnant (NP) controls.
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Increased expression and phosphorylation of 6-phosphofructo-2-kinase/fructose-2,6-bisphosphatase isoforms in urinary exosomes in pre-eclampsia
Journal of translational medicine, 2019Co-Authors: R Ellis, Marina Katerelos, Suetwan Choy, Natasha Cook, Mardiana Lee, Kathy Paizis, Gabrielle Pell, Sue Walker, David A Power, Peter F MountAbstract:Background Glycolysis is altered in various Kidney diseases, but little is known about glycolysis in pre-eclampsia, a multi-system disorder with major pathological effects on the Kidney. Urinary exosomes provide a non-invasive alternative for studying changes in Kidney Metabolism. This study aims to characterise the expression and phosphorylation of isozymes of the key glycolytic regulatory protein, 6-phosphofructokinase-2-kinase/fructose-2,6-bisphosphatase (PFK-2/FBPase-2), in urinary exosomes of subjects with pre-eclampsia (PE), compared to normotensive non-pregnant (NC) and normotensive pregnant (NP) controls.
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Increased expression and phosphorylation of 6-phosphofructo-2-kinase/fructose-2,6-bisphosphatase isoforms in urinary exosomes in pre-eclampsia
BMC, 2019Co-Authors: R Ellis, Marina Katerelos, Suetwan Choy, Natasha Cook, Mardiana Lee, Kathy Paizis, Gabrielle Pell, Sue Walker, David A Power, Peter F MountAbstract:Abstract Background Glycolysis is altered in various Kidney diseases, but little is known about glycolysis in pre-eclampsia, a multi-system disorder with major pathological effects on the Kidney. Urinary exosomes provide a non-invasive alternative for studying changes in Kidney Metabolism. This study aims to characterise the expression and phosphorylation of isozymes of the key glycolytic regulatory protein, 6-phosphofructokinase-2-kinase/fructose-2,6-bisphosphatase (PFK-2/FBPase-2), in urinary exosomes of subjects with pre-eclampsia (PE), compared to normotensive non-pregnant (NC) and normotensive pregnant (NP) controls. Methods A cross-sectional study of NC (n = 19), NP (n = 23) and PE (n = 29) subjects was performed. Exosomes were isolated from urine samples by differential ultracentrifugation, and then analyzed by Western blot and densitometry for expression of PFK-2/FBPase-2 isozymes (PFKFB2, PFKFB3 and PFKFB4) and phosphorylation of PFKFB2 at residues Ser483 and Ser466 and PFKFB3 at Ser461. Results PFKFB2 expression was increased 4.7-fold in PE compared to NP (p
José L. Soengas - One of the best experts on this subject based on the ideXlab platform.
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Carbohydrate Metabolism in several tissues of rainbow trout, Oncorhynchus mykiss, is modified during ovarian recrudescence
Comparative Biochemistry and Physiology Part B: Comparative Biochemistry, 1993Co-Authors: P. Barciela, José L. Soengas, P. Rey, Manuel Aldegunde, G. RozasAbstract:Abstract 1. 1. Several pathways of carbohydrate Metabolism were evaluated in three different tissues—liver, gonad and Kidney—of a hatchery-reared population of rainbow trout ( Oncorhynchus mykiss ) which characterised two different stages of their gonadal maturation, i.e. previtellogenesis and established exogenous vitellogenesis. 2. 2. A fall in liver glycogen levels was observed during exogenous vitellogenesis. A decrease in activity of the enzymes involved in glycolysis and in the pentose phosphate shunt was also observed, suggesting that at the end of exogenous vitellogenesis the necessity of energy and reducing power has decreased compared to the situation at the onset of this period. 3. 3. The main changes observed in gonad during vitellogenesis were the decreased activity of glycolysis and the pentose phosphate shunt as well as increased glycogen levels. The stored glycogen should be used later in association with the embryo development. 4. 4. No major changes were observed in Kidney Metabolism throughout the vitellogenic process. 5. 5. Exogenous vitellogenesis in rainbow trout is mainly associated with increased glycogen levels in the gonad and decreased metabolic activity in the liver.
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Changes in carbohydrate Metabolism related to the onset of ovarian recrudescence in dmesticated rainbow trout (Oncorhynchus mykiss)
Comparative Biochemistry and Physiology Part A: Physiology, 1993Co-Authors: José L. Soengas, P. Barciela, Manuel Aldegunde, B. Sanmartín, G. RozasAbstract:Abstract 1. 1. A study of several carbohydrate Metabolism pathways was carried out in three different tissues—liver, gonad and Kidney—from domesticated female rainbow trout ( Oncorhynchus mykiss ) at three different stages ofgonadal maturation, i.e. previtellogenesis, endogenous vitellogenesis and the onset of exogenous vitellogenesis. 2. 2. A fall in liver glycogen levels was observed at the beginning of gonadal recrudescence. The glucose obtained by glycogen rupture appears to be used both in liver glycolysis and in generating reducing power. In addition, a decrease in both the use of exogenous glucose and gluconeogenesis was also observed. 3. 3. A large increase in gonad glucose levels was observed at the beginning of gonadal recrudescence. This increase may be due to both a higher use of exogenous glucose (from diet and other tissues) and an increased gluconeogenesis. The higher glucose levels appear to be used not only in glycogen synthesis, but also in producing reducing power. 4. 4. No changes were observed in Kidney Metabolism that could be related to the initial stages ofgonadal maturation. 5. 5. The onset of the gonadal recrudescence in female rainbow trout is mainly associated with a higher use of glucose in the gonad and increased metabolic activity in the liver.
