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Effective Delivery of Endogenous Antioxidants Ameliorates Diabetic Nephropathy

BACKGROUND: Diabetic nephropathy (DN) is thought to be partially due to the injury of renal cells and the renal micro-environment by free radicals. Free radial scavenging agents that inhibit free radical damage may well prevent the development of underlying conditions such as mesangial expansion (by...

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Autores principales: Park, Yongsoo, Kim, Hyunok, Park, Leejin, Min, Dongsoo, Park, Jinseu, Choi, Sooyoung, Park, Moon Hyang
Formato: Online Artículo Texto
Lenguaje:English
Publicado: Public Library of Science 2015
Materias:
Acceso en línea:https://www.ncbi.nlm.nih.gov/pmc/articles/PMC4483240/
https://www.ncbi.nlm.nih.gov/pubmed/26114547
http://dx.doi.org/10.1371/journal.pone.0130815
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author Park, Yongsoo
Kim, Hyunok
Park, Leejin
Min, Dongsoo
Park, Jinseu
Choi, Sooyoung
Park, Moon Hyang
author_facet Park, Yongsoo
Kim, Hyunok
Park, Leejin
Min, Dongsoo
Park, Jinseu
Choi, Sooyoung
Park, Moon Hyang
author_sort Park, Yongsoo
collection PubMed
description BACKGROUND: Diabetic nephropathy (DN) is thought to be partially due to the injury of renal cells and the renal micro-environment by free radicals. Free radial scavenging agents that inhibit free radical damage may well prevent the development of underlying conditions such as mesangial expansion (by inhibiting extracellular matrix expression) in these patients. METHODS: Using techniques for intra-cellular delivery of peptides, we made metallothionein (MT) and superoxide dismutase (SOD), potent endogenous antioxidants, readily transducible into cell membrane and tested their protective effect against the development of DN in OLETF rats. Herein, we study antioxidant peptides for their ability to prevent oxidative damage to primary rat mesangial cells (MCs), which are important constituents of renal glomeruli. RESULTS: Intraperitoneal administration of these antioxidants resulted in delivery to the kidney and decreased ROS and the expression of downstream signals in renal cells and postponed the usual progression to DN. In in vitro experiments, MT and SOD were efficiently transferred to MCs, and the increased removal of ROS by MT and SOD was proportional to the degree of scavenging enzymes delivered. MT and SOD decreased three major oxidative injuries (hyperglycemia, AGE and ROS exposure) and also injuries directly mediated by angiotensin II in MCs while changing downstream signal transduction. CONCLUSIONS: The protective effects of MT and SOD for the progression of DN in experimental animals may be associated with the scavenging of ROS by MT and SOD and correlated changes in signal transduction downstream. Concomitant administration of these antioxidant peptides may prove to be a new approach for the prevention and therapy of DN.
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spelling pubmed-44832402015-06-29 Effective Delivery of Endogenous Antioxidants Ameliorates Diabetic Nephropathy Park, Yongsoo Kim, Hyunok Park, Leejin Min, Dongsoo Park, Jinseu Choi, Sooyoung Park, Moon Hyang PLoS One Research Article BACKGROUND: Diabetic nephropathy (DN) is thought to be partially due to the injury of renal cells and the renal micro-environment by free radicals. Free radial scavenging agents that inhibit free radical damage may well prevent the development of underlying conditions such as mesangial expansion (by inhibiting extracellular matrix expression) in these patients. METHODS: Using techniques for intra-cellular delivery of peptides, we made metallothionein (MT) and superoxide dismutase (SOD), potent endogenous antioxidants, readily transducible into cell membrane and tested their protective effect against the development of DN in OLETF rats. Herein, we study antioxidant peptides for their ability to prevent oxidative damage to primary rat mesangial cells (MCs), which are important constituents of renal glomeruli. RESULTS: Intraperitoneal administration of these antioxidants resulted in delivery to the kidney and decreased ROS and the expression of downstream signals in renal cells and postponed the usual progression to DN. In in vitro experiments, MT and SOD were efficiently transferred to MCs, and the increased removal of ROS by MT and SOD was proportional to the degree of scavenging enzymes delivered. MT and SOD decreased three major oxidative injuries (hyperglycemia, AGE and ROS exposure) and also injuries directly mediated by angiotensin II in MCs while changing downstream signal transduction. CONCLUSIONS: The protective effects of MT and SOD for the progression of DN in experimental animals may be associated with the scavenging of ROS by MT and SOD and correlated changes in signal transduction downstream. Concomitant administration of these antioxidant peptides may prove to be a new approach for the prevention and therapy of DN. Public Library of Science 2015-06-26 /pmc/articles/PMC4483240/ /pubmed/26114547 http://dx.doi.org/10.1371/journal.pone.0130815 Text en © 2015 Park et al http://creativecommons.org/licenses/by/4.0/ This is an open-access article distributed under the terms of the Creative Commons Attribution License, which permits unrestricted use, distribution, and reproduction in any medium, provided the original author and source are properly credited.
spellingShingle Research Article
Park, Yongsoo
Kim, Hyunok
Park, Leejin
Min, Dongsoo
Park, Jinseu
Choi, Sooyoung
Park, Moon Hyang
Effective Delivery of Endogenous Antioxidants Ameliorates Diabetic Nephropathy
title Effective Delivery of Endogenous Antioxidants Ameliorates Diabetic Nephropathy
title_full Effective Delivery of Endogenous Antioxidants Ameliorates Diabetic Nephropathy
title_fullStr Effective Delivery of Endogenous Antioxidants Ameliorates Diabetic Nephropathy
title_full_unstemmed Effective Delivery of Endogenous Antioxidants Ameliorates Diabetic Nephropathy
title_short Effective Delivery of Endogenous Antioxidants Ameliorates Diabetic Nephropathy
title_sort effective delivery of endogenous antioxidants ameliorates diabetic nephropathy
topic Research Article
url https://www.ncbi.nlm.nih.gov/pmc/articles/PMC4483240/
https://www.ncbi.nlm.nih.gov/pubmed/26114547
http://dx.doi.org/10.1371/journal.pone.0130815
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