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P.p. De Deyn - One of the best experts on this subject based on the ideXlab platform.
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Effect of NaCN on currents evoked by uremic retention solutes in dissociated mouse neurons.
Brain research, 2004Co-Authors: A Torremans, Bart Marescau, Rudi D'hooge, P.p. De Deyn, G. Van De Vijver, Raymond Vanholder, Norbert Lameire, P.p. Van BogaertAbstract:Uremic retention solutes possibly contribute to neuronal hypoxia/ischemia and its consequences in patients with renal failure. We examined the in vitro effects of several uremic retention solutes on murine central neurons under chemically induced metabolic hypoxia by application of sodium cyanide (NaCN). Whole cell currents were recorded using the tight-seal whole-cell voltage clamp technique. Application of NaCN caused an inward whole-cell current. From all tested toxins, which included several indoles, guanidino compounds, polyamines, purines, phenols, DL-homocysteine, orotate and myoinositol, only creatinine (CTN), guanidine (G) and Guanidinosuccinic Acid (GSA) produced a significant current in control and hypoxic neurons. Current evoked by GSA was significantly increased in the chemical hypoxic condition, and a synergistic effect of GSA and spermine was observed in hypoxic neurons.
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The effect of high protein diet on urea and guanidino compound levels in renal insufficient mice
Amino Acids, 2001Co-Authors: M. Al Banchaabouchi, B Marescau, R. D'hooge, P.p. De DeynAbstract:Nephrectomy in mice provokes a decrease in creatinine clearance (CTN_Cl) and an increase in urea and specific guanidino compound (GC) concentrations in blood and other tissues. Our purpose was to investigate the influence of high protein diet (HPD) on CTN_Cl, urea and GC levels in NX mice. Mice were nephrectomized or sham-operated and subdivided in groups to study five diet conditions. At the end of each experiment, 10 days and 30 days postsurgery, urine and blood were collected for determination of urea and GCs, including creatinine. HPD resulted in significantly higher CTN_Cl values in sham-operated mice than those observed in mice under normal protein diet, 10 days as well as 30 days postnephrectomy. HPD induced significant increases in plasma urea, Guanidinosuccinic Acid, argininic Acid and α -keto- δ -guanidinovaleric Acid concentration 10 days postsurgery but not 30 days postsurgery. HPD coincided with significantly higher excretion of urea, Guanidinosuccinic Acid, α -keto- δ -guanidinovaleric Acid, creatine, argininic Acid and γ -guanidinobutyric Acid in sham-operated and nephrectomized mice 10 days postsurgery. Our results show that HPD induces supplementary (to nephrectomy) increases of urea and GCs in the early postsurgery period but not in the later phase.
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Uraemic guanidino compounds inhibit γ-aminobutyric Acid-evoked whole cell currents in mouse spinal cord neurones
Neuroscience letters, 1999Co-Authors: Rudi D'hooge, P.p. De Deyn, G. Van De Vijver, Gudrun Antoons, Adam Raes, P.p. Van BogaertAbstract:Abstract Guanidine, creatinine (CTN), methylguanidine (MG) and Guanidinosuccinic Acid (GSA) are four endogenous guanidino compounds with proven neuroexcitatory actions, and putative pathophysiological significance as uraemic toxins. The effects of these uraemic guanidino compounds, were studied on whole-cell current evoked by γ -amino butyric Acid (GABA) on mouse spinal cord neurones in vitro. CTN, MG and GSA concentration dependently blocked GABA-evoked current with calculated IC 50 values (± SE) of 9.6±0.9, 9.7±1.5 and 5.1±0.4 mM, respectively. CTN, MG and GSA were shown to block inward and outward currents to the same extent, demonstrating voltage independent block of GABA-evoked current by these compounds. Guanidine, however, evoked inward whole-cell currents, which were almost completely blocked by strychnine, indicating that the guanidine-evoked current might have been due to glycine receptor activation.
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Effect of endotoxemia on plasma and tissue levels of nitric oxide metabolites and guanidino compounds.
Archives of physiology and biochemistry, 1997Co-Authors: D. R. Deshmukh, Bart Marescau, V. S. Ghole, P.p. De DeynAbstract:The effect of endotoxemia on the levels of amino Acids, nitrates, nitrites and guanidino compounds was investigated. Plasma levels of nitrate and nitrite were significantly increased indicating increased production of nitric oxide during endotoxemia. Plasma concentrations of alanine, glutamine, leucine, methionine, phenylalanine, proline and taurine were also significantly elevated. These results indicate that endotoxin produces a hypercatabolic state. The plasma concentration of arginine was significantly decreased whereas the concentrations of ornithine and urea, the catabolites of arginine were increased. Decreased plasma arginine coupled with increased plasma ornithine and urea indicate that arginine catabolism is increased and arginine synthesis is decreased during endotoxemia. Plasma levels of creatine, creatinine, guanidine and Guanidinosuccinic Acid were significantly elevated whereas homoarginine levels were significantly decreased. Nitric oxide synthase utilizes arginine as well as homoarginine ...
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Epileptiform activity and hippocampal damage produced by intrahippocampal injection of Guanidinosuccinic Acid in rat
Neuroscience letters, 1996Co-Authors: J. C. Pan, Rudi D'hooge, Y.-q. Pei, L. Lai, P.p. De DeynAbstract:Abstract Guanidinosuccinic Acid (GSA) is a guanidino compound found in mammalian central nervous system and physiological fluids. Its level has been found to be. greatly increased in serum and cerebrospinal fluid of patients with renal failure, and the compound is suggested to play a role in uremic encephalopathy. In this report we examined the behavioral, electrographic and morphological effects of intrahippocampal GSA injection in unanesthetized rats. Intrahippocampal administration of 2 μl GSA solution (3.5 nM) was followed by behavior observation, and electrohippocampographic and electrocorticographic recording. GSA-injected animals showed partial clonic seizures leading to generalized clonic seizures, and eventually status epilepticus. These were accompanied by epileptiform electrographic discharges. During generalized clonic seizures, the electrohippocampogram showed arythmic bursting spikes. Epileptiform electric activity persisted even after the generalized clonic convulsions had stopped, and lasted until the animals were killed, 5 days following injection. Microscopic examination of brain slices of these rats revealed severe neural damage in CA1 area of hippocampus. Treatment of rats with the non-competitive NMDA receptor antagonist ketamine prevented both partial and generalized clonic seizures, epileptiform electrographic; discharges, and GSA-induced hippocampal damage.
Rudi D'hooge - One of the best experts on this subject based on the ideXlab platform.
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Effect of NaCN on currents evoked by uremic retention solutes in dissociated mouse neurons.
Brain research, 2004Co-Authors: A Torremans, Bart Marescau, Rudi D'hooge, P.p. De Deyn, G. Van De Vijver, Raymond Vanholder, Norbert Lameire, P.p. Van BogaertAbstract:Uremic retention solutes possibly contribute to neuronal hypoxia/ischemia and its consequences in patients with renal failure. We examined the in vitro effects of several uremic retention solutes on murine central neurons under chemically induced metabolic hypoxia by application of sodium cyanide (NaCN). Whole cell currents were recorded using the tight-seal whole-cell voltage clamp technique. Application of NaCN caused an inward whole-cell current. From all tested toxins, which included several indoles, guanidino compounds, polyamines, purines, phenols, DL-homocysteine, orotate and myoinositol, only creatinine (CTN), guanidine (G) and Guanidinosuccinic Acid (GSA) produced a significant current in control and hypoxic neurons. Current evoked by GSA was significantly increased in the chemical hypoxic condition, and a synergistic effect of GSA and spermine was observed in hypoxic neurons.
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Uraemic guanidino compounds inhibit γ-aminobutyric Acid-evoked whole cell currents in mouse spinal cord neurones
Neuroscience letters, 1999Co-Authors: Rudi D'hooge, P.p. De Deyn, G. Van De Vijver, Gudrun Antoons, Adam Raes, P.p. Van BogaertAbstract:Abstract Guanidine, creatinine (CTN), methylguanidine (MG) and Guanidinosuccinic Acid (GSA) are four endogenous guanidino compounds with proven neuroexcitatory actions, and putative pathophysiological significance as uraemic toxins. The effects of these uraemic guanidino compounds, were studied on whole-cell current evoked by γ -amino butyric Acid (GABA) on mouse spinal cord neurones in vitro. CTN, MG and GSA concentration dependently blocked GABA-evoked current with calculated IC 50 values (± SE) of 9.6±0.9, 9.7±1.5 and 5.1±0.4 mM, respectively. CTN, MG and GSA were shown to block inward and outward currents to the same extent, demonstrating voltage independent block of GABA-evoked current by these compounds. Guanidine, however, evoked inward whole-cell currents, which were almost completely blocked by strychnine, indicating that the guanidine-evoked current might have been due to glycine receptor activation.
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Epileptiform activity and hippocampal damage produced by intrahippocampal injection of Guanidinosuccinic Acid in rat
Neuroscience letters, 1996Co-Authors: J. C. Pan, Rudi D'hooge, Y.-q. Pei, L. Lai, P.p. De DeynAbstract:Abstract Guanidinosuccinic Acid (GSA) is a guanidino compound found in mammalian central nervous system and physiological fluids. Its level has been found to be. greatly increased in serum and cerebrospinal fluid of patients with renal failure, and the compound is suggested to play a role in uremic encephalopathy. In this report we examined the behavioral, electrographic and morphological effects of intrahippocampal GSA injection in unanesthetized rats. Intrahippocampal administration of 2 μl GSA solution (3.5 nM) was followed by behavior observation, and electrohippocampographic and electrocorticographic recording. GSA-injected animals showed partial clonic seizures leading to generalized clonic seizures, and eventually status epilepticus. These were accompanied by epileptiform electrographic discharges. During generalized clonic seizures, the electrohippocampogram showed arythmic bursting spikes. Epileptiform electric activity persisted even after the generalized clonic convulsions had stopped, and lasted until the animals were killed, 5 days following injection. Microscopic examination of brain slices of these rats revealed severe neural damage in CA1 area of hippocampus. Treatment of rats with the non-competitive NMDA receptor antagonist ketamine prevented both partial and generalized clonic seizures, epileptiform electrographic; discharges, and GSA-induced hippocampal damage.
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Guanidino compound levels in brain regions of non-dialyzed uremic patients
Neurochemistry international, 1995Co-Authors: P.p. De Deyn, Bart Marescau, Rudi D'hooge, I. Possemiers, J. Nagler, Ch. MahlerAbstract:Abstract Guanidino compounds have been suggested to contribute to the complex neurological complications associated with uremia. Several of them have previously been reported to accumulate in physiological fluids of renal insufficient subjects. We report on guanidino compound levels in 28 brain regions in control and uremic brains. In all brain regions studied, in controls as well as in uremic patients, concentrations of α-keto-δ-guanidinovalefic Acid, α-N-acetylarginine and β-guanidinopropionic Acid remained below detection limits. Creatine, guanidinoacetic Acid, argininic Acid, γ-guanidinobutyric Acid, arginine and homoarginine were not increased in uremic patients. Argininic Acid and homoarginine were detectable in some brain regions only. Creatine concentrations varied from 2500±2100 nmol/g tissue in hypophysis to 10500±1200 nmol/g tissue in cerebellar cortex. Even more pronounced regional differences were found for γ-guanidinobutyric Acid with the lowest concentration in the caudate nucleus (0.6±0.3 nmol/g tissue) and highest in substantia nigra, pallidum and cerebellar dentate nucleus (8.3±2.8 nmol/g tissue). The Guanidinosuccinic Acid levels were below detection limit in controls in the majority of brain regions. Taking into account the detection limit of Guanidinosuccinic Acid for a certain amount of tissue applied to the analytical system, important increases (approx. up to > 100 fold) were observed in all brain regions of uremic patients. Accumulation of Guanidinosuccinic Acid increased with increasing degree of renal failure with levels up to 65 nmol/g tissue in the hypophysis. Creatinine concentrations were also found to be increased in uremic brain regions but increases seemed to be less strictly related to serum urea levels. Guanidine and methylguanidine were found only occasionally in brain regions of controls while respectively 100- and 30-fold increases were found in brain regions of uremic subjects. Levels of Guanidinosuccinic Acid and creatinine in uremic brain were comparable to those previously observed in brain of experimental animals displaying convulsions following intraperitoneal injection of the respective compounds. Our findings further establish guanidino compounds as probable uremic toxins contributing to the neurological complications in uremia.
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The uremic guanidino compound Guanidinosuccinic Acid induces behavioral convulsions and concomitant epileptiform electrocorticographic discharges in mice.
Brain research, 1992Co-Authors: Rudi D'hooge, Y.-q. Pei, Jacqueline Manil, P.p. De DeynAbstract:Abstract As yet, the in vivo epileptogenic properties of Guanidinosuccinic Acid (GSA) remained highly conjectural, still requiring the demonstration of GSA-induced behavioral convulsions accompanied by epileptiform electrographic discharges. Therefore, Swiss mice were injected intraperitoneally (i.p.) with increasing doses of GSA. Full-blown clonic or clonic-tonic convulsions appeared in a dose-dependent manner, with a median latency of about 25 min. CD 50 (convulsive dose of the drug in 50% of the animals), the LD 50 (lethal dose in 50%), and their 95% confidence limits for GSA suspensions in i.p. administration were 363 (287–458) mg/kg and 579 (445–756) mg/kg, respectively. In addition, four-channel electrocorticographic (ECoG) recordings were made in freely moving mice following the injection of 700 mg/kg (CD 97 ). Epileptiform ECoG discharges coincided with the behavioral manifestation of the GSA-induced convulsions starting with initial decrease in amplitude, occasional spike-waves (10–20 min after injection), eventually leading to sustained spiking and spike-wave activity (30–50 min after injection). Clonic convulsions induced by a CD 97 dose of GSA were only moderately attenuated by high doses of i.p. phenobarbital (20, 40 and 80 mg/kg), while tonic extension and lethal effects were dose-dependently blocked. A dose of 1000 mg/kg (CD 97 for tonic extension) induced tonic extension in 100% of the animals, following treatment with 20 mg/kg of phenytoin none of the animals displayed tonic extension, and following 10 mg/kg only 30% of the animals displayed tonic extension, while the occurrence of clonic convulsions was not significantly attenuated.
Bart Marescau - One of the best experts on this subject based on the ideXlab platform.
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Effect of NaCN on currents evoked by uremic retention solutes in dissociated mouse neurons.
Brain research, 2004Co-Authors: A Torremans, Bart Marescau, Rudi D'hooge, P.p. De Deyn, G. Van De Vijver, Raymond Vanholder, Norbert Lameire, P.p. Van BogaertAbstract:Uremic retention solutes possibly contribute to neuronal hypoxia/ischemia and its consequences in patients with renal failure. We examined the in vitro effects of several uremic retention solutes on murine central neurons under chemically induced metabolic hypoxia by application of sodium cyanide (NaCN). Whole cell currents were recorded using the tight-seal whole-cell voltage clamp technique. Application of NaCN caused an inward whole-cell current. From all tested toxins, which included several indoles, guanidino compounds, polyamines, purines, phenols, DL-homocysteine, orotate and myoinositol, only creatinine (CTN), guanidine (G) and Guanidinosuccinic Acid (GSA) produced a significant current in control and hypoxic neurons. Current evoked by GSA was significantly increased in the chemical hypoxic condition, and a synergistic effect of GSA and spermine was observed in hypoxic neurons.
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Effect of endotoxemia on plasma and tissue levels of nitric oxide metabolites and guanidino compounds.
Archives of physiology and biochemistry, 1997Co-Authors: D. R. Deshmukh, Bart Marescau, V. S. Ghole, P.p. De DeynAbstract:The effect of endotoxemia on the levels of amino Acids, nitrates, nitrites and guanidino compounds was investigated. Plasma levels of nitrate and nitrite were significantly increased indicating increased production of nitric oxide during endotoxemia. Plasma concentrations of alanine, glutamine, leucine, methionine, phenylalanine, proline and taurine were also significantly elevated. These results indicate that endotoxin produces a hypercatabolic state. The plasma concentration of arginine was significantly decreased whereas the concentrations of ornithine and urea, the catabolites of arginine were increased. Decreased plasma arginine coupled with increased plasma ornithine and urea indicate that arginine catabolism is increased and arginine synthesis is decreased during endotoxemia. Plasma levels of creatine, creatinine, guanidine and Guanidinosuccinic Acid were significantly elevated whereas homoarginine levels were significantly decreased. Nitric oxide synthase utilizes arginine as well as homoarginine ...
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Guanidino compound levels in brain regions of non-dialyzed uremic patients
Neurochemistry international, 1995Co-Authors: P.p. De Deyn, Bart Marescau, Rudi D'hooge, I. Possemiers, J. Nagler, Ch. MahlerAbstract:Abstract Guanidino compounds have been suggested to contribute to the complex neurological complications associated with uremia. Several of them have previously been reported to accumulate in physiological fluids of renal insufficient subjects. We report on guanidino compound levels in 28 brain regions in control and uremic brains. In all brain regions studied, in controls as well as in uremic patients, concentrations of α-keto-δ-guanidinovalefic Acid, α-N-acetylarginine and β-guanidinopropionic Acid remained below detection limits. Creatine, guanidinoacetic Acid, argininic Acid, γ-guanidinobutyric Acid, arginine and homoarginine were not increased in uremic patients. Argininic Acid and homoarginine were detectable in some brain regions only. Creatine concentrations varied from 2500±2100 nmol/g tissue in hypophysis to 10500±1200 nmol/g tissue in cerebellar cortex. Even more pronounced regional differences were found for γ-guanidinobutyric Acid with the lowest concentration in the caudate nucleus (0.6±0.3 nmol/g tissue) and highest in substantia nigra, pallidum and cerebellar dentate nucleus (8.3±2.8 nmol/g tissue). The Guanidinosuccinic Acid levels were below detection limit in controls in the majority of brain regions. Taking into account the detection limit of Guanidinosuccinic Acid for a certain amount of tissue applied to the analytical system, important increases (approx. up to > 100 fold) were observed in all brain regions of uremic patients. Accumulation of Guanidinosuccinic Acid increased with increasing degree of renal failure with levels up to 65 nmol/g tissue in the hypophysis. Creatinine concentrations were also found to be increased in uremic brain regions but increases seemed to be less strictly related to serum urea levels. Guanidine and methylguanidine were found only occasionally in brain regions of controls while respectively 100- and 30-fold increases were found in brain regions of uremic subjects. Levels of Guanidinosuccinic Acid and creatinine in uremic brain were comparable to those previously observed in brain of experimental animals displaying convulsions following intraperitoneal injection of the respective compounds. Our findings further establish guanidino compounds as probable uremic toxins contributing to the neurological complications in uremia.
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Behavioral toxicity of Guanidinosuccinic Acid in adult and young mice.
Toxicology letters, 1992Co-Authors: Rudi D'hooge, Bart Marescau, Y.-q. Pei, Peter Paul De DeynAbstract:Abstract Guanidinosuccinic Acid (GSA), a guanidino compound found to be greatly increased in uremia, was administered by intraperitoneal (i.p.) injection to adult albino mice and to young mice 7,14 and 21 days old. Epileptogenic and toxic properties were assessed and GSA brain levels following i.p. injection were determined. In adult mice, GSA induced long-lasting generalized clonic and clonic-tonic convulsions in a dose-dependent manner with a CD 50 (and 95% confidence interval) of 363 (287–458) mg/kg ( n = 35), and an LD 50 of 579 (445–756) mg/kg. The CD 50 of GSA corresponded with a brain concentration of 56 nmol/g tissue. Electrocorticographic recording infive adult mice revealed epileptiform discharges (spikes, spike-waves, and polyspike-waves) which appeared concomitant with the convulsions. When young mice were i.p. injected with a (for adults) subconvulsive dose of GSA (250 mg/kg), an age-dependent decrease was noted in GSA-induced convulsions and in the resulting brain concentration. The presented findings suggest that GSA could be an important uremic toxin which could contribute to the epileptic symptomatology in uremia.
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The pathobiochemistry of uremia and hyperargininemia further demonstrates a metabolic relationship between urea and Guanidinosuccinic Acid.
Metabolism: clinical and experimental, 1992Co-Authors: Bart Marescau, Peter Paul De Deyn, I.a. Qureshi, Marc E. De Broe, Italo Antonozzi, Stephen D. Cederbaum, Roberto Cerone, N. Chamoles, Rosa Gatti, Soo Sang KangAbstract:To better understand the biosynthesis of Guanidinosuccinic Acid, we determined urea, arginine, and Guanidinosuccinic Acid levels in nondialyzed uremic and hyperargininemic patients. These substances were also determined during several years of therapy in one hyperargininemic patient. Interrelationships of Guanidinosuccinic Acid levels with their corresponding urea and arginine levels were assessed by linear correlation studies. In uremic patients, a significant positive linear correlation (r = .821, p < .001) was found between serum urea and Guanidinosuccinic Acid levels. A significant positive linear correlation was also found between serum urea levels and urinary Guanidinosuccinic Acid levels (r = .828, P < .001), but not between serum arginine levels and urinary Guanidinosuccinic Acid levels in hyperargininemic patients. In the intrahyperargininemic patient study, a similar significant positive correlation was found between serum urea levels and the corresponding urinary Guanidinosuccinic Acid levels (r = .866, P < .001); the correlation between serum arginine levels and the corresponding urinary Guanidinosuccinic Acid levels was smaller. The presented analytical findings in uremic and hyperargininemic patients clearly demonstrate a metabolic relationship between urea and Guanidinosuccinic Acid.
Itsuo Nishioka - One of the best experts on this subject based on the ideXlab platform.
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uraemic toxin reduction a newly found effect of hydrolysable type tannin containing crude drug and gallotannin
Phytotherapy Research, 1995Co-Authors: Takako Yokozawa, Koji Fujioka, Hikokichi Oura, Takashi Tanaka, Gen-ichiro Nonaka, Itsuo NishiokaAbstract:The levels of urea nitrogen, creatinine, methylguanidine and Guanidinosuccinic Acid, which accumulate in blood in parallel with the progress of renal failure after adenine administration, were decreased significantly in rats given Galla Rhois, Moutan Cortex or Paeoniae Radix extract. Administration of Galla Rhois extract was found to be more effective than the other two crude drugs in decreasing the uraemic toxin parameters. A uraemic toxin-decreasing effect similar to that of crude drug was also obtained using 1,3,6-tri-O-galloyl-β-D-glucopyranose and 1,2,3,4,6-penta-O-galloyl-β-D-glucopyranose.
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Decrease in uraemic toxins, a newly found beneficial effect of Ephedrae Herba
Phytotherapy Research, 1995Co-Authors: Takako Yokozawa, Koji Fujioka, Hikokichi Oura, Takashi Tanaka, Gen-ichiro Nonaka, Itsuo NishiokaAbstract:The levels of urea nitrogen, creatinine, methylguanidine and Guanidinosuccinic Acid, which accumulate in the blood in parallel with the progress of renal failure after adenine administration, were decreased markedly and significantly in rats given Ephedrae Herba extract. Administration of the fraction III of Ephedrae Herba extract was found to be more effective than any of the other fractions in decreasing uraemic toxin parameters. Analysis of the fractions by means of thin layer chromatography revealed that the fraction III contains condensed tannin.
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Renal responses to magnesium lithospermate B in rats with adenine-induced renal failure
Phytotherapy Research, 1993Co-Authors: Takako Yokozawa, Hikokichi Oura, Gen-ichiro Nonaka, Tae Woong Lee, Masao Hattori, Itsuo NishiokaAbstract:A study was conducted to investigate the effects of magnesium lithospermate B on the uraemic symptoms and development of hypertension in rats with adenine-induced renal failure. Chronic administration of 10 mg/kg body weight/day magnesium lithospermate B significantly reduced serum urea nitrogen, creatinine, methylguanidine, Guanidinosuccinic Acid and inorganic phosphate, accompanied by increased urinary excretion of urea, creatinine and electrolytes. In addition, renal tissue blood flow was significantly increased and mean blood pressure significantly decreased in the magnesium lithospermate B-treated group compared with the control group. These results confirm that chronic administration of magnesium lithospermate B to rats with adenine-induced renal failure ameliorates the uraemic symptoms and development of hypertension by improving renal haemodynamics and electrolyte metabolism.
Peter Paul De Deyn - One of the best experts on this subject based on the ideXlab platform.
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The pathobiochemistry of uremia and hyperargininemia further demonstrates a metabolic relationship between urea and Guanidinosuccinic Acid.
Metabolism: clinical and experimental, 1992Co-Authors: Bart Marescau, Peter Paul De Deyn, I.a. Qureshi, Marc E. De Broe, Italo Antonozzi, Stephen D. Cederbaum, Roberto Cerone, N. Chamoles, Rosa Gatti, Soo Sang KangAbstract:To better understand the biosynthesis of Guanidinosuccinic Acid, we determined urea, arginine, and Guanidinosuccinic Acid levels in nondialyzed uremic and hyperargininemic patients. These substances were also determined during several years of therapy in one hyperargininemic patient. Interrelationships of Guanidinosuccinic Acid levels with their corresponding urea and arginine levels were assessed by linear correlation studies. In uremic patients, a significant positive linear correlation (r = .821, p < .001) was found between serum urea and Guanidinosuccinic Acid levels. A significant positive linear correlation was also found between serum urea levels and urinary Guanidinosuccinic Acid levels (r = .828, P < .001), but not between serum arginine levels and urinary Guanidinosuccinic Acid levels in hyperargininemic patients. In the intrahyperargininemic patient study, a similar significant positive correlation was found between serum urea levels and the corresponding urinary Guanidinosuccinic Acid levels (r = .866, P < .001); the correlation between serum arginine levels and the corresponding urinary Guanidinosuccinic Acid levels was smaller. The presented analytical findings in uremic and hyperargininemic patients clearly demonstrate a metabolic relationship between urea and Guanidinosuccinic Acid.
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Behavioral toxicity of Guanidinosuccinic Acid in adult and young mice.
Toxicology letters, 1992Co-Authors: Rudi D'hooge, Bart Marescau, Y.-q. Pei, Peter Paul De DeynAbstract:Abstract Guanidinosuccinic Acid (GSA), a guanidino compound found to be greatly increased in uremia, was administered by intraperitoneal (i.p.) injection to adult albino mice and to young mice 7,14 and 21 days old. Epileptogenic and toxic properties were assessed and GSA brain levels following i.p. injection were determined. In adult mice, GSA induced long-lasting generalized clonic and clonic-tonic convulsions in a dose-dependent manner with a CD 50 (and 95% confidence interval) of 363 (287–458) mg/kg ( n = 35), and an LD 50 of 579 (445–756) mg/kg. The CD 50 of GSA corresponded with a brain concentration of 56 nmol/g tissue. Electrocorticographic recording infive adult mice revealed epileptiform discharges (spikes, spike-waves, and polyspike-waves) which appeared concomitant with the convulsions. When young mice were i.p. injected with a (for adults) subconvulsive dose of GSA (250 mg/kg), an age-dependent decrease was noted in GSA-induced convulsions and in the resulting brain concentration. The presented findings suggest that GSA could be an important uremic toxin which could contribute to the epileptic symptomatology in uremia.
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Effect of ammonium acetate-induced hyperammonemia on metabolism of guanidino compounds
Biochemical medicine and metabolic biology, 1991Co-Authors: Kathleen L. Meert, Devendra R. Deshmukh, Bart Marescau, Peter Paul De Deyn, Ashok P. SarnaikAbstract:Abstract Guanidino compounds are synthesized from arginine in various tissues such as liver, kidney, brain, and skeletal muscle. Guanidino compounds such as arginine and creatine play an important role in nitrogen metabolism, whereas other guanidino compounds such as Guanidinosuccinic Acid and α-N-acetylarginine are known toxins. In order to understand the changes in the metabolism of guanidino compounds during ammonia toxicity, we investigated the effect of hyperammonemia induced by an ammonium acetate injection on the levels of guanidino compounds in plasma, liver, kidney, and brain of rats. Control animals were injected with an equal volume of saline. Blood and tissues were removed 1 h following ammonium acetate or saline injection and guanidino compounds were analyzed by high-performance liquid chromatography. Plasma and kidney levels of Guanidinosuccinic Acid were significantly elevated in rats challenged with ammonium acetate. Brain α-N-acetylarginine levels were also significantly higher in rats injected with ammonium acetate as compared to those in controls. Our results suggest that Guanidinosuccinic Acid and α-N-acetylarginine may play an important role in hyperammonemia.
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Guanidinosuccinic Acid inhibits excitatory synaptic transmission in CA1 region of rat hippocampal slices.
Annals of neurology, 1991Co-Authors: Rudi D'hooge, Jacqueline Manil, Fernand Colin, Peter Paul De DeynAbstract:SCOPUS: le.jFLWNAinfo:eu-repo/semantics/publishe
