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Late administration of Mn porphyrin-based SOD mimic enhances diabetic complications.

Ali DK, Oriowo M, Tovmasyan A, Batinic-Haberle I, Benov L - Redox Biol (2013)

Bottom Line: The effect of the treatment on activities of glutathione peroxidase, superoxide dismutase, catalase, glutathione reductase, glucose-6-phosphate dehydrogenase, glyceraldehyde-3-phosphate dehydrogenase, and glyoxalases I and II as well as malondialdehyde and GSH/GSSG ratio were determined in kidneys.Our data showed that delayed administration of MnTM-2-PyP(5+) did not protect against oxidative damage and did not prevent diabetic complications.The data support the concept that the overall biological effect of a redox-active MnP is determined by (i) the relative concentrations of oxidants and reductants, i.e. the cellular redox environment and (ii) MnP biodistribution.

View Article: PubMed Central - PubMed

Affiliation: Department of Biochemistry, Faculty of Medicine, Kuwait University, P.O. Box 24923, Safat 13110, Kuwait.

ABSTRACT
Mn(III) N-alkylpyridylporphyrins (MnPs) have demonstrated protection in various conditions where increased production of reactive oxygen/reactive nitrogen species (ROS/RNS), is a key pathological factors. MnPs can produce both pro-oxidative and antioxidative effects depending upon the cellular redox environment that they encounter. Previously we reported (Free Radic. Res. 39: 81-8, 2005) that when the treatment started at the onset of diabetes, Mn(III) meso-tetrakis(N-methylpyridinium-2-yl)porphyrin, MnTM-2-PyP(5+) suppressed diabetes-induced oxidative stress. Diabetes, however, is rarely diagnosed at its onset. The aim of this study was to investigate if MnTM-2-PyP(5+) can suppress oxidative damage and prevent diabetic complications when administered more than a week after the onset of diabetes. Diabetes was induced by streptozotocin. The MnP-based treatment started 8 days after the onset of diabetes and continued for 2 months. The effect of the treatment on activities of glutathione peroxidase, superoxide dismutase, catalase, glutathione reductase, glucose-6-phosphate dehydrogenase, glyceraldehyde-3-phosphate dehydrogenase, and glyoxalases I and II as well as malondialdehyde and GSH/GSSG ratio were determined in kidneys. Kidney function was assessed by measuring lysozyme and total protein in urine and blood urea nitrogen. Vascular damage was evaluated by assessing vascular reactivity. Our data showed that delayed administration of MnTM-2-PyP(5+) did not protect against oxidative damage and did not prevent diabetic complications. Moreover, MnTM-2-PyP(5+) contributed to the kidney damage, which seems to be a consequence of its pro-oxidative action. Such outcome can be explained by advanced oxidative damage which already existed at the moment the therapy with MnP started. The data support the concept that the overall biological effect of a redox-active MnP is determined by (i) the relative concentrations of oxidants and reductants, i.e. the cellular redox environment and (ii) MnP biodistribution.

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Mn porphyrin-based SOD mimic enhances diabetes-induced kidney damage. The effect of MnTM-2-PyP treatment on hyperglycemia-induced kidney damage was evaluated by measuring (A) urinary protein, (B) blood urea nitrogen and (C) lysozyme content in urine. Groups are: C – Control; C+MnP – Control+MnTM-2-PyP; D – Diabetic; D+MnP – Diabetic+MnTM-2-PyP. ⁎P<0.05 compared to control, ⁎⁎P<0.05 compared to Diabetic.
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f0015: Mn porphyrin-based SOD mimic enhances diabetes-induced kidney damage. The effect of MnTM-2-PyP treatment on hyperglycemia-induced kidney damage was evaluated by measuring (A) urinary protein, (B) blood urea nitrogen and (C) lysozyme content in urine. Groups are: C – Control; C+MnP – Control+MnTM-2-PyP; D – Diabetic; D+MnP – Diabetic+MnTM-2-PyP. ⁎P<0.05 compared to control, ⁎⁎P<0.05 compared to Diabetic.

Mentions: The effect of MnTM-2-PyP on hyperglycemia-induced kidney damage was determined by assessing the total protein and lysozyme content in urine. Similarly to the above listed findings, no positive effect of the MnP treatment on diabetes-induced proteinuria was observed (Fig. 3). The MnP treatment actually caused an increase in urinary protein, which, however was statistically insignificant. The treatment increased the excretion of lysozyme, which is a marker of impaired tubular reabsorption of low molecular weight proteins (Fig. 3). This coincided with increased blood urea nitrogen levels in the diabetic rats, which was further significantly augmented by the treatment (Fig. 3).


Late administration of Mn porphyrin-based SOD mimic enhances diabetic complications.

Ali DK, Oriowo M, Tovmasyan A, Batinic-Haberle I, Benov L - Redox Biol (2013)

Mn porphyrin-based SOD mimic enhances diabetes-induced kidney damage. The effect of MnTM-2-PyP treatment on hyperglycemia-induced kidney damage was evaluated by measuring (A) urinary protein, (B) blood urea nitrogen and (C) lysozyme content in urine. Groups are: C – Control; C+MnP – Control+MnTM-2-PyP; D – Diabetic; D+MnP – Diabetic+MnTM-2-PyP. ⁎P<0.05 compared to control, ⁎⁎P<0.05 compared to Diabetic.
© Copyright Policy - open-access
Related In: Results  -  Collection

License
Show All Figures
getmorefigures.php?uid=PMC3815015&req=5

f0015: Mn porphyrin-based SOD mimic enhances diabetes-induced kidney damage. The effect of MnTM-2-PyP treatment on hyperglycemia-induced kidney damage was evaluated by measuring (A) urinary protein, (B) blood urea nitrogen and (C) lysozyme content in urine. Groups are: C – Control; C+MnP – Control+MnTM-2-PyP; D – Diabetic; D+MnP – Diabetic+MnTM-2-PyP. ⁎P<0.05 compared to control, ⁎⁎P<0.05 compared to Diabetic.
Mentions: The effect of MnTM-2-PyP on hyperglycemia-induced kidney damage was determined by assessing the total protein and lysozyme content in urine. Similarly to the above listed findings, no positive effect of the MnP treatment on diabetes-induced proteinuria was observed (Fig. 3). The MnP treatment actually caused an increase in urinary protein, which, however was statistically insignificant. The treatment increased the excretion of lysozyme, which is a marker of impaired tubular reabsorption of low molecular weight proteins (Fig. 3). This coincided with increased blood urea nitrogen levels in the diabetic rats, which was further significantly augmented by the treatment (Fig. 3).

Bottom Line: The effect of the treatment on activities of glutathione peroxidase, superoxide dismutase, catalase, glutathione reductase, glucose-6-phosphate dehydrogenase, glyceraldehyde-3-phosphate dehydrogenase, and glyoxalases I and II as well as malondialdehyde and GSH/GSSG ratio were determined in kidneys.Our data showed that delayed administration of MnTM-2-PyP(5+) did not protect against oxidative damage and did not prevent diabetic complications.The data support the concept that the overall biological effect of a redox-active MnP is determined by (i) the relative concentrations of oxidants and reductants, i.e. the cellular redox environment and (ii) MnP biodistribution.

View Article: PubMed Central - PubMed

Affiliation: Department of Biochemistry, Faculty of Medicine, Kuwait University, P.O. Box 24923, Safat 13110, Kuwait.

ABSTRACT
Mn(III) N-alkylpyridylporphyrins (MnPs) have demonstrated protection in various conditions where increased production of reactive oxygen/reactive nitrogen species (ROS/RNS), is a key pathological factors. MnPs can produce both pro-oxidative and antioxidative effects depending upon the cellular redox environment that they encounter. Previously we reported (Free Radic. Res. 39: 81-8, 2005) that when the treatment started at the onset of diabetes, Mn(III) meso-tetrakis(N-methylpyridinium-2-yl)porphyrin, MnTM-2-PyP(5+) suppressed diabetes-induced oxidative stress. Diabetes, however, is rarely diagnosed at its onset. The aim of this study was to investigate if MnTM-2-PyP(5+) can suppress oxidative damage and prevent diabetic complications when administered more than a week after the onset of diabetes. Diabetes was induced by streptozotocin. The MnP-based treatment started 8 days after the onset of diabetes and continued for 2 months. The effect of the treatment on activities of glutathione peroxidase, superoxide dismutase, catalase, glutathione reductase, glucose-6-phosphate dehydrogenase, glyceraldehyde-3-phosphate dehydrogenase, and glyoxalases I and II as well as malondialdehyde and GSH/GSSG ratio were determined in kidneys. Kidney function was assessed by measuring lysozyme and total protein in urine and blood urea nitrogen. Vascular damage was evaluated by assessing vascular reactivity. Our data showed that delayed administration of MnTM-2-PyP(5+) did not protect against oxidative damage and did not prevent diabetic complications. Moreover, MnTM-2-PyP(5+) contributed to the kidney damage, which seems to be a consequence of its pro-oxidative action. Such outcome can be explained by advanced oxidative damage which already existed at the moment the therapy with MnP started. The data support the concept that the overall biological effect of a redox-active MnP is determined by (i) the relative concentrations of oxidants and reductants, i.e. the cellular redox environment and (ii) MnP biodistribution.

Show MeSH
Related in: MedlinePlus