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Abstract Title:

Geraniol protects against cyclosporine A-induced renal injury in rats: Role of Wnt/β-catenin and PPARγ signaling pathways.

Abstract Source:

Life Sci. 2022 Feb 15 ;291:120259. Epub 2021 Dec 28. PMID: 34968469

Abstract Author(s):

Nevertyty M Mahmoud, Shimaa M Elshazly, Samar Rezq

Article Affiliation:

Nevertyty M Mahmoud

Abstract:

AIMS: The nephrotoxicity of cyclosporine A (CsA) limits its use as an immunosuppressant. Wnt/β-catenin signaling is involved in the pathogenesis of both acute and chronic kidney disease, and it is inhibited by peroxisome proliferator-activated receptor gamma (PPARγ). We aimed to evaluate if geraniol, which can modulate both PPARγ 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 PPARγ 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-κB), apoptosis (caspase-3), extracellular matrix remodeling [matrix metalloproteinase-9 (MMP-9)], and fibrosis (TGF-β1, Smad3, and Smad7) were assessed. Renal histological analysis, Wnt signaling components (Wnt-4/β-catenin and E-cadherin), and PPARγ 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 andβ-catenin expression and E-cadherin down-regulation), and lower PPARγ 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/β-catenin and the increase in PPARγ 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.

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