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G B Ryan - One of the best experts on this subject based on the ideXlab platform.
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Biphasic glomerular hypertrophy in rats administered Puromycin Aminonucleoside
Kidney international, 1996Co-Authors: Meroë M. Cahill, G B Ryan, John F BertramAbstract:Biphasic glomerular hypertrophy in rats administered Puromycin Aminonucleoside. Recent evidence suggests that glomerular hypertrophy is a key event in the development of focal and segmental glomerulosclerosis and hyalinosis (FSGS) in humans and in many experimental models of FSGS. The initial aim of the present study was to determine if glomerular hypertrophy occurs in a Puromycin Aminonucleoside (PAN) model of FSGS, previously considered not to involve glomerular hypertrophy. Upon identifying significant glomerular hypertrophy, our second aim was to determine the contribution of glomerular capillary growth to this hypertrophy. Female Sprague-Dawley rats (approximately 200 g) were administered either PAN (2mg/100g body wt) subcutaneously, or an equivalent volume of 0.9% saline at weeks 0, 1, 2, 4, 6, 8 and 10. Tissue was analyzed at weeks 7 and 13. Unbiased stereological methods were used to estimate a range of glomerular parameters. Mean glomerular tuft volume in PAN-treated rats was 48% greater than in saline-treated rats at seven weeks, and 63% greater at 13 weeks. Similar results were found for mean renal corpuscle volume. FSGS was absent at seven weeks and minor at 13 weeks. Two-way analysis of variance indicated: significant effects ( P
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Podocyte architecture in Puromycin Aminonucleoside-treated rats administered tungsten or allopurinol.
Experimental nephrology, 1995Co-Authors: Sharon D Ricardo, John F Bertram, G B RyanAbstract:The role of xanthine oxidase as a source of reactive oxygen species in Puromycin Aminonucleoside nephrosis was examined. The effects of allopurinol (a xanthine oxidase inhibitor as well as a reactive oxygen species scavenging enzyme) and tungsten (a specific xanthine oxidase inhibitor) on glomerular epithelial cell ultrastructure, renal xanthine oxidase and xanthine dehydrogenase activity, and urinary protein excretion were examined in Puromycin Aminonucleoside-treated rats. Co-administration of allopurinol to such rats reduced proteinuria by approximately 70% over the 10 days studied, and reduced the degree of glomerular epithelial cell foot process effacement at both 5 and 10 days, compared to rats that received Puromycin Aminonucleoside alone. Unexpectedly, co-administration of allopurinol to Puromycin Aminonucleoside-treated rats did not reduce xanthine oxidase activity; however, the combined activity of xanthine oxidase and xanthine dehydrogenase in such animals was reduced on day 5. Co-administration of tungsten to Puromycin Aminonucleoside-treated rats did not reduce proteinuria or alter the number of filtration slits. Rats co-administered tungsten and Puromycin Aminonucleoside had significantly reduced renal xanthine oxidase and combined xanthine oxidase and xanthine dehydrogenase activities on days 5 and 10, compared to rats treated with Puromycin Aminonucleoside alone. These results provide evidence that the protection provided by allopurinol in Puromycin Aminonucleoside-treated rats is due to the antioxidant properties of allopurinol, rather than to its activities as a xanthine oxidase inhibitor.
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antioxidants protect podocyte foot processes in Puromycin Aminonucleoside treated rats
Journal of The American Society of Nephrology, 1994Co-Authors: Sharon D Ricardo, John F Bertram, G B RyanAbstract:Whether a reduction in urinary protein excretion in rats coadministered Puromycin Aminonucleoside and antioxidants was associated with a reduction in alterations to glomerular epithelial cell (podocyte) ultrastructure was examined. Daily urinary protein excretion was measured in rats that received a single i.v. injection of saline or Puromycin Aminonucleoside with or without coadministration of antioxidants. The coadministration of alpha-tocopherol/ascorbic acid, dimethyl thiourea, or superoxide dismutase to Puromycin Aminonucleoside-treated rats reduced proteinuria by approximately 90, 40, and 60%, respectively, over the 18-day period studied. For a second group of rats, daily urinary protein excretion was measured and kidneys were processed for light microscopy and transmission and scanning electron microscopy 4, 5, and 10 days after injection. Transmission electron microscopic morphometric analysis of glomeruli from Puromycin Aminonucleoside-treated rats coadministered antioxidants revealed significantly reduced foot process effacement on Days, 4, 5, and 10 compared with rats that received Puromycin Aminonucleoside alone. Thus, at Day 10, Puromycin Aminonucleoside-treated rats coadministered alpha-tocopherol/ascorbic acid, dimethyl thiourea, or superoxide dismutase contained 90, 74, and 88% (P
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Antioxidants protect podocyte foot processes in Puromycin Aminonucleoside-treated rats.
Journal of the American Society of Nephrology : JASN, 1994Co-Authors: Sharon D Ricardo, John F Bertram, G B RyanAbstract:Whether a reduction in urinary protein excretion in rats coadministered Puromycin Aminonucleoside and antioxidants was associated with a reduction in alterations to glomerular epithelial cell (podocyte) ultrastructure was examined. Daily urinary protein excretion was measured in rats that received a single i.v. injection of saline or Puromycin Aminonucleoside with or without coadministration of antioxidants. The coadministration of alpha-tocopherol/ascorbic acid, dimethyl thiourea, or superoxide dismutase to Puromycin Aminonucleoside-treated rats reduced proteinuria by approximately 90, 40, and 60%, respectively, over the 18-day period studied. For a second group of rats, daily urinary protein excretion was measured and kidneys were processed for light microscopy and transmission and scanning electron microscopy 4, 5, and 10 days after injection. Transmission electron microscopic morphometric analysis of glomeruli from Puromycin Aminonucleoside-treated rats coadministered antioxidants revealed significantly reduced foot process effacement on Days, 4, 5, and 10 compared with rats that received Puromycin Aminonucleoside alone. Thus, at Day 10, Puromycin Aminonucleoside-treated rats coadministered alpha-tocopherol/ascorbic acid, dimethyl thiourea, or superoxide dismutase contained 90, 74, and 88% (P < 0.01 in all cases) more glomerular epithelial cell filtration slits per unit length of glomerular basement membrane than rats treated with Puromycin Aminonucleoside alone. In contrast, by scanning electron microscopy, the antioxidants were found to provide no protection against the changes occurring in glomerular epithelial cell bodies and major processes. These results provide further evidence of a role for reactive oxygen species in Puromycin Aminonucleoside nephrosis and indicate that the antioxidants provide protection against the changes occurring in glomerular epithelial cell foot processes.
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Reactive oxygen species in Puromycin Aminonucleoside nephrosis: In vitro studies
Kidney international, 1994Co-Authors: Sharon D Ricardo, John F Bertram, G B RyanAbstract:Reactive oxygen species in Puromycin Aminonucleoside nephrosis: In vitro studies. We examined the role of reactive oxygen species (ROS) in Puromycin Aminonucleoside (PAN)-induced changes to glomerular epithelial cells (GECs) in vitro . Levels of superoxide anion (O 2 •− ), hydrogen peroxide (H 2 O 2 ) and hydroxyl radical (HO • ) were measured in rat kidney-slice cultures containing PAN with or without antioxidants (allopurinol, probucol and α-tocopherol/ascorbic acid). GEC morphology was assessed after three days of culture using transmission (TEM) and scanning (SEM) electron microscopy. The effects of hypoxanthine on GEC ultrastructure was also assessed. O 2 •− , H 2 O 2 and HO • were generated when PAN was added to kidney-slice cultures in Medium 199. TEM morphometry revealed that incubation with PAN (100 µg/ml) significantly (P in vitro . When the hydrophobic antioxidants probucol or α-tocopherol/ascorbic acid, which scavenged/inhibited generation of O 2 •− , H 2 O 2 and HO • , were added to cultures containing PAN, the effect of PAN on foot processes was abolished. The TEM appearance of GECs now resembled that seen in control cultures. On the other hand, SEM revealed that probucol and α-tocopherol/ascorbic acid provided no protection against the changes induced by PAN in GEC cell bodies or major processes. Allopurinol provided no protection against the changes induced by PAN in GEC cell bodies, major processes or foot processes. The addition of hypoxanthine to kidney-slice cultures did not result in the generation of O 2 •− , H 2 O 2 or HO • , or alter GEC ultrastructure. These findings indicate that ROS play a role in PAN-induced alterations to GEC foot process architecture in vitro . However, the xanthine oxidase pathway does not appear to play a major role in generating ROS from PAN in vitro .
Sharon D Ricardo - One of the best experts on this subject based on the ideXlab platform.
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Podocyte architecture in Puromycin Aminonucleoside-treated rats administered tungsten or allopurinol.
Experimental nephrology, 1995Co-Authors: Sharon D Ricardo, John F Bertram, G B RyanAbstract:The role of xanthine oxidase as a source of reactive oxygen species in Puromycin Aminonucleoside nephrosis was examined. The effects of allopurinol (a xanthine oxidase inhibitor as well as a reactive oxygen species scavenging enzyme) and tungsten (a specific xanthine oxidase inhibitor) on glomerular epithelial cell ultrastructure, renal xanthine oxidase and xanthine dehydrogenase activity, and urinary protein excretion were examined in Puromycin Aminonucleoside-treated rats. Co-administration of allopurinol to such rats reduced proteinuria by approximately 70% over the 10 days studied, and reduced the degree of glomerular epithelial cell foot process effacement at both 5 and 10 days, compared to rats that received Puromycin Aminonucleoside alone. Unexpectedly, co-administration of allopurinol to Puromycin Aminonucleoside-treated rats did not reduce xanthine oxidase activity; however, the combined activity of xanthine oxidase and xanthine dehydrogenase in such animals was reduced on day 5. Co-administration of tungsten to Puromycin Aminonucleoside-treated rats did not reduce proteinuria or alter the number of filtration slits. Rats co-administered tungsten and Puromycin Aminonucleoside had significantly reduced renal xanthine oxidase and combined xanthine oxidase and xanthine dehydrogenase activities on days 5 and 10, compared to rats treated with Puromycin Aminonucleoside alone. These results provide evidence that the protection provided by allopurinol in Puromycin Aminonucleoside-treated rats is due to the antioxidant properties of allopurinol, rather than to its activities as a xanthine oxidase inhibitor.
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antioxidants protect podocyte foot processes in Puromycin Aminonucleoside treated rats
Journal of The American Society of Nephrology, 1994Co-Authors: Sharon D Ricardo, John F Bertram, G B RyanAbstract:Whether a reduction in urinary protein excretion in rats coadministered Puromycin Aminonucleoside and antioxidants was associated with a reduction in alterations to glomerular epithelial cell (podocyte) ultrastructure was examined. Daily urinary protein excretion was measured in rats that received a single i.v. injection of saline or Puromycin Aminonucleoside with or without coadministration of antioxidants. The coadministration of alpha-tocopherol/ascorbic acid, dimethyl thiourea, or superoxide dismutase to Puromycin Aminonucleoside-treated rats reduced proteinuria by approximately 90, 40, and 60%, respectively, over the 18-day period studied. For a second group of rats, daily urinary protein excretion was measured and kidneys were processed for light microscopy and transmission and scanning electron microscopy 4, 5, and 10 days after injection. Transmission electron microscopic morphometric analysis of glomeruli from Puromycin Aminonucleoside-treated rats coadministered antioxidants revealed significantly reduced foot process effacement on Days, 4, 5, and 10 compared with rats that received Puromycin Aminonucleoside alone. Thus, at Day 10, Puromycin Aminonucleoside-treated rats coadministered alpha-tocopherol/ascorbic acid, dimethyl thiourea, or superoxide dismutase contained 90, 74, and 88% (P
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Antioxidants protect podocyte foot processes in Puromycin Aminonucleoside-treated rats.
Journal of the American Society of Nephrology : JASN, 1994Co-Authors: Sharon D Ricardo, John F Bertram, G B RyanAbstract:Whether a reduction in urinary protein excretion in rats coadministered Puromycin Aminonucleoside and antioxidants was associated with a reduction in alterations to glomerular epithelial cell (podocyte) ultrastructure was examined. Daily urinary protein excretion was measured in rats that received a single i.v. injection of saline or Puromycin Aminonucleoside with or without coadministration of antioxidants. The coadministration of alpha-tocopherol/ascorbic acid, dimethyl thiourea, or superoxide dismutase to Puromycin Aminonucleoside-treated rats reduced proteinuria by approximately 90, 40, and 60%, respectively, over the 18-day period studied. For a second group of rats, daily urinary protein excretion was measured and kidneys were processed for light microscopy and transmission and scanning electron microscopy 4, 5, and 10 days after injection. Transmission electron microscopic morphometric analysis of glomeruli from Puromycin Aminonucleoside-treated rats coadministered antioxidants revealed significantly reduced foot process effacement on Days, 4, 5, and 10 compared with rats that received Puromycin Aminonucleoside alone. Thus, at Day 10, Puromycin Aminonucleoside-treated rats coadministered alpha-tocopherol/ascorbic acid, dimethyl thiourea, or superoxide dismutase contained 90, 74, and 88% (P < 0.01 in all cases) more glomerular epithelial cell filtration slits per unit length of glomerular basement membrane than rats treated with Puromycin Aminonucleoside alone. In contrast, by scanning electron microscopy, the antioxidants were found to provide no protection against the changes occurring in glomerular epithelial cell bodies and major processes. These results provide further evidence of a role for reactive oxygen species in Puromycin Aminonucleoside nephrosis and indicate that the antioxidants provide protection against the changes occurring in glomerular epithelial cell foot processes.
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Reactive oxygen species in Puromycin Aminonucleoside nephrosis: In vitro studies
Kidney international, 1994Co-Authors: Sharon D Ricardo, John F Bertram, G B RyanAbstract:Reactive oxygen species in Puromycin Aminonucleoside nephrosis: In vitro studies. We examined the role of reactive oxygen species (ROS) in Puromycin Aminonucleoside (PAN)-induced changes to glomerular epithelial cells (GECs) in vitro . Levels of superoxide anion (O 2 •− ), hydrogen peroxide (H 2 O 2 ) and hydroxyl radical (HO • ) were measured in rat kidney-slice cultures containing PAN with or without antioxidants (allopurinol, probucol and α-tocopherol/ascorbic acid). GEC morphology was assessed after three days of culture using transmission (TEM) and scanning (SEM) electron microscopy. The effects of hypoxanthine on GEC ultrastructure was also assessed. O 2 •− , H 2 O 2 and HO • were generated when PAN was added to kidney-slice cultures in Medium 199. TEM morphometry revealed that incubation with PAN (100 µg/ml) significantly (P in vitro . When the hydrophobic antioxidants probucol or α-tocopherol/ascorbic acid, which scavenged/inhibited generation of O 2 •− , H 2 O 2 and HO • , were added to cultures containing PAN, the effect of PAN on foot processes was abolished. The TEM appearance of GECs now resembled that seen in control cultures. On the other hand, SEM revealed that probucol and α-tocopherol/ascorbic acid provided no protection against the changes induced by PAN in GEC cell bodies or major processes. Allopurinol provided no protection against the changes induced by PAN in GEC cell bodies, major processes or foot processes. The addition of hypoxanthine to kidney-slice cultures did not result in the generation of O 2 •− , H 2 O 2 or HO • , or alter GEC ultrastructure. These findings indicate that ROS play a role in PAN-induced alterations to GEC foot process architecture in vitro . However, the xanthine oxidase pathway does not appear to play a major role in generating ROS from PAN in vitro .
John F Bertram - One of the best experts on this subject based on the ideXlab platform.
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Biphasic glomerular hypertrophy in rats administered Puromycin Aminonucleoside
Kidney international, 1996Co-Authors: Meroë M. Cahill, G B Ryan, John F BertramAbstract:Biphasic glomerular hypertrophy in rats administered Puromycin Aminonucleoside. Recent evidence suggests that glomerular hypertrophy is a key event in the development of focal and segmental glomerulosclerosis and hyalinosis (FSGS) in humans and in many experimental models of FSGS. The initial aim of the present study was to determine if glomerular hypertrophy occurs in a Puromycin Aminonucleoside (PAN) model of FSGS, previously considered not to involve glomerular hypertrophy. Upon identifying significant glomerular hypertrophy, our second aim was to determine the contribution of glomerular capillary growth to this hypertrophy. Female Sprague-Dawley rats (approximately 200 g) were administered either PAN (2mg/100g body wt) subcutaneously, or an equivalent volume of 0.9% saline at weeks 0, 1, 2, 4, 6, 8 and 10. Tissue was analyzed at weeks 7 and 13. Unbiased stereological methods were used to estimate a range of glomerular parameters. Mean glomerular tuft volume in PAN-treated rats was 48% greater than in saline-treated rats at seven weeks, and 63% greater at 13 weeks. Similar results were found for mean renal corpuscle volume. FSGS was absent at seven weeks and minor at 13 weeks. Two-way analysis of variance indicated: significant effects ( P
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Podocyte architecture in Puromycin Aminonucleoside-treated rats administered tungsten or allopurinol.
Experimental nephrology, 1995Co-Authors: Sharon D Ricardo, John F Bertram, G B RyanAbstract:The role of xanthine oxidase as a source of reactive oxygen species in Puromycin Aminonucleoside nephrosis was examined. The effects of allopurinol (a xanthine oxidase inhibitor as well as a reactive oxygen species scavenging enzyme) and tungsten (a specific xanthine oxidase inhibitor) on glomerular epithelial cell ultrastructure, renal xanthine oxidase and xanthine dehydrogenase activity, and urinary protein excretion were examined in Puromycin Aminonucleoside-treated rats. Co-administration of allopurinol to such rats reduced proteinuria by approximately 70% over the 10 days studied, and reduced the degree of glomerular epithelial cell foot process effacement at both 5 and 10 days, compared to rats that received Puromycin Aminonucleoside alone. Unexpectedly, co-administration of allopurinol to Puromycin Aminonucleoside-treated rats did not reduce xanthine oxidase activity; however, the combined activity of xanthine oxidase and xanthine dehydrogenase in such animals was reduced on day 5. Co-administration of tungsten to Puromycin Aminonucleoside-treated rats did not reduce proteinuria or alter the number of filtration slits. Rats co-administered tungsten and Puromycin Aminonucleoside had significantly reduced renal xanthine oxidase and combined xanthine oxidase and xanthine dehydrogenase activities on days 5 and 10, compared to rats treated with Puromycin Aminonucleoside alone. These results provide evidence that the protection provided by allopurinol in Puromycin Aminonucleoside-treated rats is due to the antioxidant properties of allopurinol, rather than to its activities as a xanthine oxidase inhibitor.
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antioxidants protect podocyte foot processes in Puromycin Aminonucleoside treated rats
Journal of The American Society of Nephrology, 1994Co-Authors: Sharon D Ricardo, John F Bertram, G B RyanAbstract:Whether a reduction in urinary protein excretion in rats coadministered Puromycin Aminonucleoside and antioxidants was associated with a reduction in alterations to glomerular epithelial cell (podocyte) ultrastructure was examined. Daily urinary protein excretion was measured in rats that received a single i.v. injection of saline or Puromycin Aminonucleoside with or without coadministration of antioxidants. The coadministration of alpha-tocopherol/ascorbic acid, dimethyl thiourea, or superoxide dismutase to Puromycin Aminonucleoside-treated rats reduced proteinuria by approximately 90, 40, and 60%, respectively, over the 18-day period studied. For a second group of rats, daily urinary protein excretion was measured and kidneys were processed for light microscopy and transmission and scanning electron microscopy 4, 5, and 10 days after injection. Transmission electron microscopic morphometric analysis of glomeruli from Puromycin Aminonucleoside-treated rats coadministered antioxidants revealed significantly reduced foot process effacement on Days, 4, 5, and 10 compared with rats that received Puromycin Aminonucleoside alone. Thus, at Day 10, Puromycin Aminonucleoside-treated rats coadministered alpha-tocopherol/ascorbic acid, dimethyl thiourea, or superoxide dismutase contained 90, 74, and 88% (P
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Antioxidants protect podocyte foot processes in Puromycin Aminonucleoside-treated rats.
Journal of the American Society of Nephrology : JASN, 1994Co-Authors: Sharon D Ricardo, John F Bertram, G B RyanAbstract:Whether a reduction in urinary protein excretion in rats coadministered Puromycin Aminonucleoside and antioxidants was associated with a reduction in alterations to glomerular epithelial cell (podocyte) ultrastructure was examined. Daily urinary protein excretion was measured in rats that received a single i.v. injection of saline or Puromycin Aminonucleoside with or without coadministration of antioxidants. The coadministration of alpha-tocopherol/ascorbic acid, dimethyl thiourea, or superoxide dismutase to Puromycin Aminonucleoside-treated rats reduced proteinuria by approximately 90, 40, and 60%, respectively, over the 18-day period studied. For a second group of rats, daily urinary protein excretion was measured and kidneys were processed for light microscopy and transmission and scanning electron microscopy 4, 5, and 10 days after injection. Transmission electron microscopic morphometric analysis of glomeruli from Puromycin Aminonucleoside-treated rats coadministered antioxidants revealed significantly reduced foot process effacement on Days, 4, 5, and 10 compared with rats that received Puromycin Aminonucleoside alone. Thus, at Day 10, Puromycin Aminonucleoside-treated rats coadministered alpha-tocopherol/ascorbic acid, dimethyl thiourea, or superoxide dismutase contained 90, 74, and 88% (P < 0.01 in all cases) more glomerular epithelial cell filtration slits per unit length of glomerular basement membrane than rats treated with Puromycin Aminonucleoside alone. In contrast, by scanning electron microscopy, the antioxidants were found to provide no protection against the changes occurring in glomerular epithelial cell bodies and major processes. These results provide further evidence of a role for reactive oxygen species in Puromycin Aminonucleoside nephrosis and indicate that the antioxidants provide protection against the changes occurring in glomerular epithelial cell foot processes.
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Reactive oxygen species in Puromycin Aminonucleoside nephrosis: In vitro studies
Kidney international, 1994Co-Authors: Sharon D Ricardo, John F Bertram, G B RyanAbstract:Reactive oxygen species in Puromycin Aminonucleoside nephrosis: In vitro studies. We examined the role of reactive oxygen species (ROS) in Puromycin Aminonucleoside (PAN)-induced changes to glomerular epithelial cells (GECs) in vitro . Levels of superoxide anion (O 2 •− ), hydrogen peroxide (H 2 O 2 ) and hydroxyl radical (HO • ) were measured in rat kidney-slice cultures containing PAN with or without antioxidants (allopurinol, probucol and α-tocopherol/ascorbic acid). GEC morphology was assessed after three days of culture using transmission (TEM) and scanning (SEM) electron microscopy. The effects of hypoxanthine on GEC ultrastructure was also assessed. O 2 •− , H 2 O 2 and HO • were generated when PAN was added to kidney-slice cultures in Medium 199. TEM morphometry revealed that incubation with PAN (100 µg/ml) significantly (P in vitro . When the hydrophobic antioxidants probucol or α-tocopherol/ascorbic acid, which scavenged/inhibited generation of O 2 •− , H 2 O 2 and HO • , were added to cultures containing PAN, the effect of PAN on foot processes was abolished. The TEM appearance of GECs now resembled that seen in control cultures. On the other hand, SEM revealed that probucol and α-tocopherol/ascorbic acid provided no protection against the changes induced by PAN in GEC cell bodies or major processes. Allopurinol provided no protection against the changes induced by PAN in GEC cell bodies, major processes or foot processes. The addition of hypoxanthine to kidney-slice cultures did not result in the generation of O 2 •− , H 2 O 2 or HO • , or alter GEC ultrastructure. These findings indicate that ROS play a role in PAN-induced alterations to GEC foot process architecture in vitro . However, the xanthine oxidase pathway does not appear to play a major role in generating ROS from PAN in vitro .
Elsa Valderrama - One of the best experts on this subject based on the ideXlab platform.
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Puromycin Aminonucleoside induces glomerular epithelial cell apoptosis
Experimental and molecular pathology, 2001Co-Authors: Vibha Sanwal, Elsa Valderrama, Manish P. Pandya, Madhu Bhaskaran, Nicholas Franki, Krishna Reddy, Guohua Ding, Aditi A. Kapasi, Pravin C. SinghalAbstract:Glomerular epithelial cell (GEC) injury has been considered to play an important role in Puromycin Aminonucleoside (PAN)-induced nephrosis. We studied the effect of PAN on rat as well as human GEC apoptosis. Morphogic evaluation of GEC apoptosis and necrosis was carried out by staining with H-33342 and propidium iodide. GEC apoptosis was further confirmed by DNA fragmentation assay (by both agarose gel electrophoresis and end-labeling). To determine the dose- and time-response effect of PAN, GECs were treated with variable concentrations of PAN (10 to 500 microg/ml) for variable time periods (6 to 48 h). To determine the role of gene synthesis, we studied the effect of actinomycin D (a transcriptional inhibitor) on PAN-induced GEC apoptosis. To determine the role of free radicals, we evaluated the effect of superoxide dismutase (SOD), dimethylthiourea (DMTU), and catalase on PAN-induced GEC apoptosis. PAN induced GEC apoptosis in a dose- and time-dependent manner. PAN at a high concentration (PAN, 100 microg/ml) also induced a moderate degree of GEC necrosis. In DNA fragmentation assays PAN-treated GECs showed the classic ladder pattern. PAN-induced GEC apoptosis was partly attenuated with free radical scavengers, such as SOD, DMTU, and catalase. In addition, actinomycin D attenuated PAN-induced GEC apoptosis. PAN induces GEC apoptosis, which may be mediated through the generation of reactive oxygen species.
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Dietary vitamin E supplementation ameliorates renal injury in chronic Puromycin Aminonucleoside nephropathy.
Journal of the American Society of Nephrology : JASN, 1995Co-Authors: Howard Trachtman, N Schwob, John Maesaka, Elsa ValderramaAbstract:Chronic Puromycin Aminonucleoside nephropathy (PAN) is an experimental analog of focal segmental glomerulosclerosis. Progressive renal damage in this model is partly mediated by excessive production of oxidant species. Whether dietary supplementation with vitamin E, an endogenous lipophilic antioxidant, ameliorates the severity of chronic PAN was tested. PAN was induced by seven serial injections of the glomerular epithelial cell toxin Puromycin Aminonucleoside, 2 mg/100 g body wt per dose, over a 12-wk period. Experimental animals (N = 8) received vitamin E-enriched chow (100 IU/kg), whereas control PAN rats (N = 10) were fed standard rodent diet containing vitamin E (30 IU/kg of chow). The administration of vitamin E had no effect on somatic growth or blood pressure; however, rats with PAN fed the vitamin E-enriched diet had an increased hematocrit. In addition, the experimental diet resulted in a 50% reduction in urinary total protein and albumin excretion and stabilization of the serum albumin, cholesterol, and triglyceride concentrations (P
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Recombinant human growth hormone exacerbates chronic Puromycin Aminonucleoside nephropathy in rats
Kidney international, 1993Co-Authors: Howard Trachtman, N Schwob, John Maesaka, Stephen Futterweit, Elsa ValderramaAbstract:Recombinant human growth hormone exacerbates chronic Puromycin Aminonucleoside nephropathy in rats. Growth failure is a cardinal feature of chronic renal failure in children. Administration of recombinant human growth hormone (rhGH) ameliorates this problem but may adversely affect the kidney and hasten the progression to end-stage renal disease. We conducted experiments to examine the impact of rhGH on the severity of chronic Puromycin Aminonucleoside (PAMN) nephropathy in rats. The glomerulopathy was induced by serial injections of PAMN over a 12 week period. Experimental animals (N = 6) received rhGH, 0.5 mg per dose, three times weekly, while control rats (N = 6) received hormone vehicle. rhGH had no effect on weight gain, hematocrit, or blood pressure in rats with the experimental renal disease. Urinary protein excretion increased approximately 50% in rhGH-treated rats with chronic PAMN nephropathy compared to untreated animals between four to eight weeks of the observation period. After 12 weeks, the inulin clearance was significantly lower in rhGH-treated rats, 0.26 ± 0.05 versus 0.50 ± 0.06 ml/min/100 g body wt in control PAMN animals, P -3 versus 11.9 ± 0.5 × 10 -3 mm 2 , P
Borje Haraldsson - One of the best experts on this subject based on the ideXlab platform.
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Permeability, Ultrastructural Changes, and Distribution of Novel Proteins in the Glomerular Barrier in Early Puromycin Aminonucleoside Nephrosis
Nephron. Experimental nephrology, 2010Co-Authors: Fredrik Dunér, Borje Haraldsson, Karin Lindström, Kjell Hultenby, Jenny Hulkko, Jaakko Patrakka, Karl Tryggvason, Annika Wernerson, Erna PetterssonAbstract:Background/Aims: It is still unclear what happens in the glomerulus when proteinuria starts. Using Puromycin Aminonucleoside nephrosis (PAN) rats, we studied early ultrastructural a
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Puromycin Aminonucleoside damages the glomerular size barrier with minimal effects on charge density
American Journal of Physiology-renal Physiology, 2001Co-Authors: Clara Hjalmarsson, Maria Ohlson, Borje HaraldssonAbstract:Puromycin Aminonucleoside (PAN) has been suggested to reduce glomerular charge density, to create large glomerular “leaks,” or not to affect the glomerular barrier. Therefore, we analyzed glomerula...
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Puromycin Aminonucleoside damages the glomerular size barrier with minimal effects on charge density
American journal of physiology. Renal physiology, 2001Co-Authors: Clara Hjalmarsson, Maria Ohlson, Borje HaraldssonAbstract:Puromycin Aminonucleoside (PAN) has been suggested to reduce glomerular charge density, to create large glomerular "leaks," or not to affect the glomerular barrier. Therefore, we analyzed glomerular charge and size selectivity in vivo and in isolated kidneys perfused at 8 degrees C (cIPK) in control and PAN-treated rats. The fractional clearances (theta) for albumin and Ficoll of similar hydrodynamic size were 0.0017 +/- 0.0004 and 0.15 +/- 0.02, respectively, in control cIPKs. Two-pore analysis gave similar results in vivo and in vitro, with small- and large-pore radii of 47-52 and 85-105 A, respectively, in controls. Puromycin increased the number of large pores 40-50 times, the total pore area over diffusion distance decreased by a factor of 25-30, and the small-pore radius increased by 33% (P < 0.001 for all comparisons of size selectivity and theta). The effect of PAN was less dramatic on the estimated wall charge density, which was 73% of that of controls. We conclude that Puromycin effectively destroys the glomerular size barrier with minimal effects on charge density.
