ReferenceID 5343
Geraniol protects against cyclosporine A-induced renal injury in rats: Role of Wnt/β-catenin and PPARγ signaling pathways
Life Sci
AIMS: The nephrotoxicity of cyclosporine A (CsA) limits its use as an immunosuppressant. Wnt/beta-catenin signaling is involved in the pathogenesis of both acute and chronic kidney disease, and it is inhibited by peroxis
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Record Fields
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- Reference Id
- 5343
- Evidence Id
- 21933
- Core Evidence Id
- 21933
- Source Reference Id
- 3938
- Herb2 Reference Id
- HBREF004735
- Subject Paper Key
- HBIN027528_34968469
- Pubmed Id
- 34968469
- Doi
- 10.1016/j.lfs.2021.120259
- Paper Title
- Geraniol protects against cyclosporine A-induced renal injury in rats: Role of Wnt/β-catenin and PPARγ signaling pathways
- Paper Abstract
- AIMS: The nephrotoxicity of cyclosporine A (CsA) limits its use as an immunosuppressant. Wnt/beta-catenin signaling is involved in the pathogenesis of both acute and chronic kidney disease, and it is inhibited by peroxisome proliferator-activated receptor gamma (PPARgamma). We aimed to evaluate if geraniol, which can modulate both PPARgamma and Wnt signaling, could protect against CsA-induced nephrotoxicity. MATERIALS AND METHODS: Rats (6 groups) received the vehicle or a combination of CsA (30 mg/kg) with the vehicle, geraniol (50, 100, or 200 mg/kg), or the PPARgamma agonist pioglitazone for 4 weeks. Blood pressure (BP), markers of renal injury (serum urea, serum creatinine, blood urea nitrogen, and urinary NAG), oxidative stress (glutathione peroxidase), inflammation (ICAM-1, IL-18, and NF-kappaB), apoptosis (caspase-3), extracellular matrix remodeling [matrix metalloproteinase-9 (MMP-9)], and fibrosis (TGF-beta1, Smad3, and Smad7) were assessed. Renal histological analysis, Wnt signaling components (Wnt-4/beta-catenin and E-cadherin), and PPARgamma expression were evaluated. KEY FINDINGS: CsA group had renal injury, as well as increased BP, renal oxidative stress, inflammation, and fibrosis. The latter changes were associated with altered renal architecture, active Wnt signaling (higher Wnt-4 and beta-catenin expression and E-cadherin down-regulation), and lower PPARgamma levels. Geraniol protected against kidney damage and the associated biochemical and histomorphological changes in a dose-dependent manner. The latter effects were comparable or superior to those of pioglitazone. SIGNIFICANCE: The down-regulation of Wnt/beta-catenin and the increase in PPARgamma by geraniol suggest that both pathways are involved in its renoprotective potential. The study highlights geraniol as a valuable protective asset against chemically induced nephrotoxicity.
- Journal
- Life Sci
- Publish Year
- 2022
- Experiment Subject
- rat
- Experiment Type
- Animal Experiment
- Phenotype Related
- Renal Injury; Inflammation; Acute And Chronic Kidney Disease; Nephrotoxicity; Fibrosis
- Paper Title Cn
- Paper Title En
- Geraniol protects against cyclosporine A-induced renal injury in rats: Role of Wnt/β-catenin and PPARγ signaling pathways
- Bilingual Status
- semi_complete