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Effective Delivery of Endogenous Antioxidants Ameliorates Diabetic Nephropathy

Title
Effective Delivery of Endogenous Antioxidants Ameliorates Diabetic Nephropathy
Author
박용수
Keywords
KAPPA-B ACTIVATION; OXIDATIVE STRESS; PROTEIN TRANSDUCTION; ENHANCED DELIVERY; MESANGIAL CELLS; METALLOTHIONEIN; KINASE; OXYGEN; COMPLICATIONS; MECHANISMS
Issue Date
2015-06
Publisher
PUBLIC LIBRARY SCIENCE
Citation
PLOS ONE, v. 10, NO 6, Page. 1-20
Abstract
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.
URI
http://journals.plos.org/plosone/article?id=10.1371/journal.pone.0130815http://hdl.handle.net/20.500.11754/25201
ISSN
1932-6203
DOI
10.1371/journal.pone.0130815
Appears in Collections:
COLLEGE OF MEDICINE[S](의과대학) > MEDICINE(의학과) > Articles
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