Reactive oxygen species/oxidative stress contributes to progression of kidney fibrosis following transient ischemic injury in mice.

Abstract

Recently, kidney fibrosis following transplantation has become recognized as a main contributor of chronic allograft nephropathy. In transplantation, transient ischemia is an inescapable event. Reactive oxygen species (ROS) play a critical role in ischemia and reperfusion (I/R)-induced acute kidney injury, as well as progression of fibrosis in various diseases such as hypertension, diabetes, and ureteral obstruction. However, a role of ROS/oxidative stress in chronic kidney fibrosis following I/R injury remains to be defined. In this study, we investigated the involvement of ROS/oxidative stress in kidney fibrosis following kidney I/R in mice. Mice were subjected to 30 min of bilateral kidney ischemia followed by reperfusion on day 0 and then administered with either manganese (III) tetrakis(1-methyl-4-pyridyl) porphyrin (MnTMPyP, 5 mg/kg body wt ip), a cell permeable superoxide dismutase (SOD) mimetic, or 0.9% saline (vehicle) beginning at 48 h after I/R for 14 days. I/R significantly increased interstitial extension, collagen deposition, apoptosis of tubular epithelial cells, nitrotyrosine expression, hydrogen peroxide production, and lipid peroxidation and decreased copper-zinc SOD, manganese SOD, and glucose 6-phosphate dehydrogenase activities in the kidneys 16 days after the procedure. MnTMPyP administration minimized these postischemic changes. In addition, MnTMPyP administration significantly attenuated the increases of alpha-smooth muscle actin, PCNA, S100A4, CD68, and heat shock protein 47 expression following I/R. We concluded that kidney fibrosis develops chronically following I/R injury, and this process is associated with the increase of ROS/oxidative stress.

• Authors: Jinu Kim, Young Mi Seok, Kyong-Jin Jung, Kwon Moo Park
• Journal: American journal of physiology. Renal physiology (Am J Physiol Renal Physiol) Vol. 297 Issue 2 Pg. F461-70 (Aug 2009) ISSN: 1522-1466 [Electronic] United States
• PMID: 19458120 (Publication Type: Journal Article, Research Support, Non-U.S. Gov't)

Chemical References

• Actins
• Antigens, CD
• Antigens, Differentiation, Myelomonocytic
• Antioxidants
• CD68 protein, mouse
• HSP47 Heat-Shock Proteins
• Metalloporphyrins
• Mn(III) 5,10,15,20-tetrakis(N-methylpyridinium-2-yl)porphyrin
• Proliferating Cell Nuclear Antigen
• Reactive Oxygen Species
• S100 Calcium-Binding Protein A4
• S100 Proteins
• S100a4 protein, mouse
• Serpinh1 protein, mouse
• Vitamin E
• 3-nitrotyrosine
• Tyrosine
• Collagen
• Hydrogen Peroxide
• Glucosephosphate Dehydrogenase
• Superoxide Dismutase

Topics

• Actins (metabolism)
• Animals
• Antigens, CD (metabolism)
• Antigens, Differentiation, Myelomonocytic (metabolism)
• Antioxidants (pharmacology)
• Apoptosis (drug effects)
• Collagen (metabolism)
• Disease Models, Animal
• Disease Progression
• Fibrosis
• Glucosephosphate Dehydrogenase (metabolism)
• HSP47 Heat-Shock Proteins (metabolism)
• Hydrogen Peroxide (metabolism)
• Ischemia (metabolism, pathology)
• Kidney (blood supply, drug effects, metabolism, pathology)
• Lipid Peroxidation (drug effects)
• Male
• Metalloporphyrins (pharmacology)
• Mice
• Mice, Inbred BALB C
• Oxidation-Reduction
• Oxidative Stress (drug effects)
• Proliferating Cell Nuclear Antigen (metabolism)
• Reactive Oxygen Species (metabolism)
• Reperfusion Injury (metabolism, pathology, prevention & control)
• S100 Calcium-Binding Protein A4
• S100 Proteins (metabolism)
• Superoxide Dismutase (metabolism)
• Time Factors
• Tyrosine (analogs & derivatives, metabolism)
• Vitamin E (pharmacology)