We found a match
Your institution may have access to this item. Find your institution then sign in to continue.
- Title
Renin-angiotensin system inhibition ameliorates CCl<sub>4</sub>-induced liver fibrosis in mice through the inactivation of nuclear transcription factor kappa B.
- Authors
Saber, Sameh; Mahmoud, Amr A.A.; Helal, Noha S.; El-Ahwany, Eman; Abdelghany, Rasha H.
- Abstract
Therapeutic interventions for liver fibrosis are still limited due to the complicated molecular pathogenesis. Renin-angiotensin system (RAS) seems to contribute to the development of hepatic fibrosis. Therefore, we aimed to examine the effect of RAS inhibition on CCl4-induced liver fibrosis. Mice were treated with silymarin (30 mg·kg−1), perindopril (1 mg·kg−1), fosinopril (2 mg·kg−1), or losartan (10 mg·kg−1). The administration of RAS inhibitors improved liver histology and decreased protein expression of alpha smooth muscle actin (α-SMA) and hepatic content of hydroxyproline. These effects found to be mediated via inactivation of nuclear transcription factor kappa B (NFκB) pathway by the inhibition of NFκB p65 phosphorylation at the Ser536 residue and phosphorylation-induced degradation of nuclear factor kappa-B inhibitor alpha (NFκBia) subsequently inhibited NFκB-induced TNF-α and TGF-β1, leading to lower levels of tissue inhibitor of metalloproteinase-1 (TIMP-1) and vascular endothelial growth factor (VEGF). We concluded that the tissue affinity of the angiotensin converting enzyme inhibitors (ACEIs) has no impact on its antifibrotic activity and that interfering the RAS either through the inhibition of ACE or the blockade of AT1R has the same therapeutic benefit. These results suggest RAS inhibitors as promising candidates for further clinical trials in the management of hepatic fibrosis.
- Subjects
RENIN-angiotensin system; HEPATIC fibrosis; LIVER histology; PROTEIN expression; ACTIN
- Publication
Canadian Journal of Physiology & Pharmacology, 2018, Vol 96, Issue 6, p569
- ISSN
0008-4212
- Publication type
Article
- DOI
10.1139/cjpp-2017-0728