REGULAR CONTENT
Final ID
425
Type
Original Scientific Research-Poster Only
Authors
B Akhavan Tafti1, S Kee2, E Lee3
Institutions
1University of California, Los Angeles, Los Angeles, CA, 2Ronald Reagan UCLA Medical Center, Los Angeles, CA, 3N/A, Los Angeles, CA
Purpose
Decreased medullary blood flow appear to be the underlying mechanism of contrast-induced nephropathy (CIN). The ensuing ischemia / hypoxia triggers rapid generation of cytotoxic reactive oxygen species, which result in apoptosis of renal tubular and glomerular cells.Protein kinase C delta (PKC-delta) is a pro-apoptotic member of PKC family that activates both extrinsic and intrinsic apoptosis pathways. It has been shown that inhibition of PKC-delta can protect different organs against ischemia / reperfusion-induced injury. Previously published studies have shown that a highly-selective peptidic inhibitor of PKC-delta can specifically inhibit this isozyme in-vivo. However, the ability of this peptide in protecting the kidneys against CIN has never been tested.Here, we present our preliminary data regarding the application of selective PKC-delta inhibitor peptides in prevention of CIN.
Materials & Methods
CIN was induced in four experimental groups of male Sprague-Dawley rats (275-300 gm) according to protocols published in the literature. Briefly, Indomethacin (10 mg/kg) was injected via tail vein followed by L-NAME (10 mg/kg) 15 minutes later. After another 10 minutes, Omnipaque 350 (1.5 mL/kg) was injected IV as the contrast agent. Animals received treatment as summarized below and were followed up for 4 days because CIN happens within the first 48-72 hours. Renal function tests were performed on a daily basis. Another group of animals without induction of CIN or receiving any treatment were included in the study as control.Study groups are summarized as follows:Group 1: Control group for baseline kidney function, no nephropathy.Group 2: CIN, treated only with daily subcutaneous saline as a surrogate to IV hydration (current standard of care).Group 3: CIN, treated with PKC-delta inhibitor.Group 4: CIN, treated with placebo.Group 5: CIN, treated with a peptide with 60% homology to PKC-delta inhibitor.
Results
Animals treated with PKC-delta inhibitor showed better renal function and less increase in serum Cr compared to placebo-treated or untreated animals.
Conclusions
PKC-delta inhibitor peptides can mitigate CIN and further studies are warranted for assessment of their potential clinical role.
Final ID
425
Type
Original Scientific Research-Poster Only
Authors
B Akhavan Tafti1, S Kee2, E Lee3
Institutions
1University of California, Los Angeles, Los Angeles, CA, 2Ronald Reagan UCLA Medical Center, Los Angeles, CA, 3N/A, Los Angeles, CA
Purpose
Decreased medullary blood flow appear to be the underlying mechanism of contrast-induced nephropathy (CIN). The ensuing ischemia / hypoxia triggers rapid generation of cytotoxic reactive oxygen species, which result in apoptosis of renal tubular and glomerular cells.Protein kinase C delta (PKC-delta) is a pro-apoptotic member of PKC family that activates both extrinsic and intrinsic apoptosis pathways. It has been shown that inhibition of PKC-delta can protect different organs against ischemia / reperfusion-induced injury. Previously published studies have shown that a highly-selective peptidic inhibitor of PKC-delta can specifically inhibit this isozyme in-vivo. However, the ability of this peptide in protecting the kidneys against CIN has never been tested.Here, we present our preliminary data regarding the application of selective PKC-delta inhibitor peptides in prevention of CIN.
Materials & Methods
CIN was induced in four experimental groups of male Sprague-Dawley rats (275-300 gm) according to protocols published in the literature. Briefly, Indomethacin (10 mg/kg) was injected via tail vein followed by L-NAME (10 mg/kg) 15 minutes later. After another 10 minutes, Omnipaque 350 (1.5 mL/kg) was injected IV as the contrast agent. Animals received treatment as summarized below and were followed up for 4 days because CIN happens within the first 48-72 hours. Renal function tests were performed on a daily basis. Another group of animals without induction of CIN or receiving any treatment were included in the study as control.Study groups are summarized as follows:Group 1: Control group for baseline kidney function, no nephropathy.Group 2: CIN, treated only with daily subcutaneous saline as a surrogate to IV hydration (current standard of care).Group 3: CIN, treated with PKC-delta inhibitor.Group 4: CIN, treated with placebo.Group 5: CIN, treated with a peptide with 60% homology to PKC-delta inhibitor.
Results
Animals treated with PKC-delta inhibitor showed better renal function and less increase in serum Cr compared to placebo-treated or untreated animals.
Conclusions
PKC-delta inhibitor peptides can mitigate CIN and further studies are warranted for assessment of their potential clinical role.