Combined therapy with melatonin and exendin-4 effectively attenuated the deterioration of renal function in rat cardiorenal syndrome.

2.50
Hdl Handle:
http://hdl.handle.net/11287/620320
Title:
Combined therapy with melatonin and exendin-4 effectively attenuated the deterioration of renal function in rat cardiorenal syndrome.
Authors:
Chen, K-H; Chen, C-H; Wallace, Christopher G ( 0000-0003-1897-9520 ) ; Chen, Y-T; Yang, C-C; Sung, P-H; Chiang, H-J; Chen, Y-L; Chua, S.; Yip, H-K; Cheng, J-T
Abstract:
This study tested the hypothesis that combined therapy with melatonin (Mel) and exendin-4 (Ex4) would be superior to either therapy alone for preventing the deterioration of renal function in cardiorenal syndrome (CRS). Male adult Sprague Dawley rats (n = 48) were randomly and equally divided into sham-control (SC), chronic kidney disease (CKD; induced by 5/6 nephrectomy), CRS (CKD + dilated cardiomyopathy, DCM; induced by doxorubicin 7 mg/kg i.p. every 5 days, 4 doses), CRS-Mel (20 mg/kg/day), CRS-Ex4 (10 µg/kg/day) and CRS-Mel-Ex4. They were euthanized by day 60 after CRS induction. By day 60, plasma creatinine level, urine protein/creatinine ratio and kidney injury histopathology score were highest in CRS, lowest in SC, and progressively decreased from CKD, CRS-Mel, CRS-Ex4 to CRS-Mel-Ex4 (all P<0.0001). The kidney protein expressions of inflammation (TNF-α/NF-κB/MMP-9/iNOS/RANTES), oxidative stress (NOX-1/NOX-2/NOX-4/oxidized protein), apoptosis (cleaved caspase-3/cleaved PARP/Bax), DNA-damaged marker (γ-H2AX) and fibrosis (p-mad3/TFG-β) showed identical patterns of creatinine level, whereas kidney protein expressions of GLP-1R showed a progressive increase from SC to CRS-Mel-Ex4 (all P<0.0001). Cellular expressions of inflammatory (CD14/CD68), DNA/kidney-damaged (γ-H2AX/KIM-1) and podocyte/renal tubule dysfunction signaling (β-catenin/Wnt1/Wnt4) biomarkers in kidney tissue exhibited an identical pattern of creatinine level (all P<0.0001). Podocyte components (podocin/dystroglycan/p-cadherin/synatopodin) were highest in SC, lowest in CRS, and significantly progressively increased from CKD to CRS-Mel-Ex4 (all P<0.0001). In conclusion, combined Mel-Ex4 therapy was superior to either one alone in preserving renal-function and kidney architectural integrity in the setting of CRS.
Citation:
Combined therapy with melatonin and exendin-4 effectively attenuated the deterioration of renal function in rat cardiorenal syndrome. 2017, 9 (2):214-229 Am J Transl Res
Publisher:
eCentury Publishing
Journal:
American journal of translational research
Issue Date:
Feb-2017
URI:
http://hdl.handle.net/11287/620320
PubMed ID:
28337255
Additional Links:
https://www.ncbi.nlm.nih.gov/pmc/articles/pmid/28337255/
Note:
This article is freely available via PubMed Central. Click on the Additional Link above to access the full-text.
Type:
Journal Article
Language:
en
Appears in Collections:
Plastic & Reconstructive Surgery; 2017 RD&E publications

Full metadata record

DC FieldValue Language
dc.contributor.authorChen, K-Hen
dc.contributor.authorChen, C-Hen
dc.contributor.authorWallace, Christopher Gen
dc.contributor.authorChen, Y-Ten
dc.contributor.authorYang, C-Cen
dc.contributor.authorSung, P-Hen
dc.contributor.authorChiang, H-Jen
dc.contributor.authorChen, Y-Len
dc.contributor.authorChua, S.en
dc.contributor.authorYip, H-Ken
dc.contributor.authorCheng, J-Ten
dc.date.accessioned2017-03-28T10:34:23Z-
dc.date.available2017-03-28T10:34:23Z-
dc.date.issued2017-02-
dc.identifier.citationCombined therapy with melatonin and exendin-4 effectively attenuated the deterioration of renal function in rat cardiorenal syndrome. 2017, 9 (2):214-229 Am J Transl Resen
dc.identifier.pmid28337255-
dc.identifier.urihttp://hdl.handle.net/11287/620320-
dc.description.abstractThis study tested the hypothesis that combined therapy with melatonin (Mel) and exendin-4 (Ex4) would be superior to either therapy alone for preventing the deterioration of renal function in cardiorenal syndrome (CRS). Male adult Sprague Dawley rats (n = 48) were randomly and equally divided into sham-control (SC), chronic kidney disease (CKD; induced by 5/6 nephrectomy), CRS (CKD + dilated cardiomyopathy, DCM; induced by doxorubicin 7 mg/kg i.p. every 5 days, 4 doses), CRS-Mel (20 mg/kg/day), CRS-Ex4 (10 µg/kg/day) and CRS-Mel-Ex4. They were euthanized by day 60 after CRS induction. By day 60, plasma creatinine level, urine protein/creatinine ratio and kidney injury histopathology score were highest in CRS, lowest in SC, and progressively decreased from CKD, CRS-Mel, CRS-Ex4 to CRS-Mel-Ex4 (all P<0.0001). The kidney protein expressions of inflammation (TNF-α/NF-κB/MMP-9/iNOS/RANTES), oxidative stress (NOX-1/NOX-2/NOX-4/oxidized protein), apoptosis (cleaved caspase-3/cleaved PARP/Bax), DNA-damaged marker (γ-H2AX) and fibrosis (p-mad3/TFG-β) showed identical patterns of creatinine level, whereas kidney protein expressions of GLP-1R showed a progressive increase from SC to CRS-Mel-Ex4 (all P<0.0001). Cellular expressions of inflammatory (CD14/CD68), DNA/kidney-damaged (γ-H2AX/KIM-1) and podocyte/renal tubule dysfunction signaling (β-catenin/Wnt1/Wnt4) biomarkers in kidney tissue exhibited an identical pattern of creatinine level (all P<0.0001). Podocyte components (podocin/dystroglycan/p-cadherin/synatopodin) were highest in SC, lowest in CRS, and significantly progressively increased from CKD to CRS-Mel-Ex4 (all P<0.0001). In conclusion, combined Mel-Ex4 therapy was superior to either one alone in preserving renal-function and kidney architectural integrity in the setting of CRS.en
dc.language.isoenen
dc.publishereCentury Publishingen
dc.relation.urlhttps://www.ncbi.nlm.nih.gov/pmc/articles/pmid/28337255/en
dc.rightsArchived with thanks to American journal of translational researchen
dc.subjectWessex Classification Subject Headings::Urology::Nephrology/Renal medicineen
dc.titleCombined therapy with melatonin and exendin-4 effectively attenuated the deterioration of renal function in rat cardiorenal syndrome.en
dc.typeJournal Articleen
dc.identifier.journalAmerican journal of translational researchen
dc.description.noteThis article is freely available via PubMed Central. Click on the Additional Link above to access the full-text.en
dc.type.versionPublisheden

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