Please use this identifier to cite or link to this item:
https://hdl.handle.net/2440/140335
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Type: | Journal article |
Title: | Relaxin elicits renoprotective actions accompanied by increasing bile acid levels in streptozotocin-induced diabetic mice |
Author: | Leo, C.H. Ou, J.L.M. Ong, E.S. Qin, C.X. Ritchie, R.H. Parry, L.J. Ng, H.H. |
Citation: | Biomedicine and Pharmacotherapy, 2023; 162:114578-1-114578-9 |
Publisher: | Elsevier BV |
Issue Date: | 2023 |
ISSN: | 0753-3322 1950-6007 |
Statement of Responsibility: | Chen Huei Leo, Jamie Li Min Ou, Eng Shi Ong, Cheng Xue Qin, Rebecca H. Ritchie, Laura J. Parry, Hooi Hooi Ng |
Abstract: | Background: The peptide hormone relaxin has potent anti-fibrotic and anti-inflammatory properties in various organs, including the kidneys. However, the protective effects of relaxin in the context of diabetic kidney complications remain controversial. Here, we aimed to evaluate the effects of relaxin treatment on key markers of kidney fibrosis, oxidative stress, and inflammation and their subsequent impact on bile acid metabolism in the streptozotocin-induced diabetes mouse model. Methods and results: Male mice were randomly allocated to placebo-treated control, placebo-treated diabetes or relaxin-treated diabetes groups (0.5 mg/kg/d, final 2 weeks of diabetes). After 12 weeks of diabetes or sham, the kidney cortex was harvested for metabolomic and gene expression analyses. Diabetic mice exhibited significant hyperglycaemia and increased circulating levels of creatine, hypoxanthine and trimethylamine N-oxide in the plasma. This was accompanied by increased expression of key markers of oxidative stress (Txnip), inflammation (Ccl2 and Il6) and fibrosis (Col1a1, Mmp2 and Fn1) in the diabetic kidney cortex. Relaxin treatment for the final 2 weeks of diabetes significantly reduced these key markers of renal fibrosis, inflammation, and oxidative stress in diabetic mice. Furthermore, relaxin treatment significantly increased the levels of bile acid metabolites, deoxycholic acid and sodium glycodeoxycholic acid, which may in part contribute to the renoprotective action of relaxin in diabetes. Conclusion: In summary, this study shows the therapeutic potential of relaxin and that it may be used as an adjunctive treatment for diabetic kidney complications. |
Keywords: | Kidney Animals Mice Diabetic Nephropathies Diabetes Mellitus, Experimental Fibrosis Inflammation Streptozocin Relaxin Oxidative Stress Male |
Rights: | © 2023 The Author(s). Published by Elsevier Masson SAS. This is an open access article under the CC BY license (http://creativecommons.org/licenses/by/4.0/). |
DOI: | 10.1016/j.biopha.2023.114578 |
Grant ID: | http://purl.org/au-research/grants/arc/LP110200543 http://purl.org/au-research/grants/nhmrc/1059660 |
Published version: | http://dx.doi.org/10.1016/j.biopha.2023.114578 |
Appears in Collections: | Medicine publications |
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File | Description | Size | Format | |
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hdl_140335.pdf | Published version | 3.05 MB | Adobe PDF | View/Open |
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