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European Journal of Pharmacology
Elsevier B.V
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Abstract: |
The main objective of this study was to determine if the telmisartan-ameliorative effects of metabolic syndrome
(MetS)-evoked nephropathy are attributed to the Hippo pathway. A secondary objective was to investigate the
potential of vitamin D3 to enhance telmisartan-favourable effects. A diet composed of 24% fat and 3% salt, along
with drinking water containing 10% fructose, was administered for 12 weeks to induce MetS. MetS-rats were
given telmisartan (5 mg/kg/day), vitamin D3 (10
μ
g/kg/day) or both by gavage, starting in the sixth week of
experimental diet administration. Assessments performed at closure included renal function, histological ex
amination, catalase, malondialdehyde (MDA), nuclear factor kappa-B (NF-κB), interleukin-6 (IL-6), peroxisome
proliferator-activated receptor-γ (PPAR-γ), phosphatase and tensin homolog (PTEN), and transforming growth
factor-β (TGF-β). Matrix metalloproteinase-9 (MMP-9) immunostaining was conducted. The expression of the
Hippo pathway components, as well as that of angiotensin II type 1 and type 2 (AT1 and AT2), receptors was
evaluated. Telmisartan attenuated MetS-evoked nephropathy, as demonstrated by improvement of renal function
and histological features, enhancement of catalase, reduction of MDA, inflammation (NF-κB, IL-6), and renal
f
ibrosis (increased PPAR-γ and PTEN and reduced MMP-9 and TGF-β). Telmisartan downregulated AT1-receptor,
upregulated AT2-receptor and restored the Hippo pathway. Vitamin D3 replicated most of the telmisartan-
elicited effects and enhanced the antifibrotic actions of telmisartan. The alleviative effects of telmisartan on
MetS-evoked nephropathy may be related to the restoration of the Hippo pathway. The combination of vitamin
D3 and telmisartan exerted more favourable effects on metabolic and nephropathic biomarkers compared with
either one administered alone.
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