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ALISKIREN AND FENOFIBRATE ATTEUATE LIVER FIBROSIS VIA TARGETING TGF- β1/ SMAD SIGNALING PATHWAY AND INDUCING HGF EXPRESSION

Article

Last updated: 13 Dec 2022

Subjects

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Tags

Liver fibrosis
Aliskiren
Fenofibrate
TGF-&beta
Samd3
ALISKIREN AND FENOFIBRATE ATTEUATE LIVER FIBROSIS VIA TARGETING TGF- β1/ SMAD SIGNALING PATHWAY AND INDUCING HGF EXPRESSION
The 1st International Online Conference Pharmaceutical and Medical Sciences: A Response to COVID-19 Theme: Support Healthcare Heroes
Pharmaceutical revolution

Abstract

Liver fibrosis stems from changes in fibrotic genes expression in response to tissue damage in various chronic liver diseases, with no effective therapeutic program at present. This study aimed to investigate the potential protective effects and the molecular targets of aliskiren (ALS) and fenofibrate (FENO) against carbon tetrachloride (CCl4)-induced liver fibrosis in rats. Wister albino rats were injected with 0.4ml/kg 50% CCl4, three times/week for 8 weeks, to induce liver fibrosis. Simultaneously, CCl4 intoxicated rats were orally administrated ALS (25mg/kg/day) and/or FENO (25mg/kg/day) for 8 weeks. Treatment with ALS and/or FENO ameliorated oxidative stress and hepatocellular damage in CCl4-intoxicated rats as indicated by the marked reduction in hepatic lipid peroxidation and serum transaminases with concomitant significant increase in hepatic superoxide dismutase (SOD) and glutathione (GSH) content. Both drugs also alleviated the severity of liver inflammation and fibrosis as evident from the significant decrease in hepatic proinflammatory and profibrotic cytokines as tumor necrosis factor-α (TNF-α), interlukin-6 (IL6), C-reactive protein (CRP), and transforming growth factor-β1 (TGF-β1) with restrain in fibrous deposit and architecture distortion that was shown upon histopathological examination. Additionally, concurrent administration of ALS with FENO downregulated hepatic p-Smad3 protein and increased hepatic growth factor (HGF) expression in CCl4-intoxicated rats. Conclusively, this study highlights the hepatoprotective effect of ALS and FENO and imply that their anti-fibrotic mechanism involves blockade of TGF-β1/Smad signaling pathway, induction of HGF expression, besides modulation of oxidative stress and inflammation.

Categories

Pharmaceutical revolution

Keywords

Liver fibrosis, Aliskiren, Fenofibrate, TGF-&beta, Samd3

Authors

First Name

Mona

Last Name

Kamal

Affiliation

Pharmacology and toxicology depart., Faculty of Pharmacy Al-Azhar University, Cairo.

Email

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City

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Orcid

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First Name

Nayira

Last Name

AbdElBaki

Affiliation

Pharmacology, Faculty of Pharmacy, AL-Azhar University, Cairo, Egypt.

Email

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City

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Orcid

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Publish Date

14 Jun 2021

Link

https://pmsazhar.conferences.ekb.eg/article_1056.html

Order

9

Publication Type

Conference

Publication Title

The 1st International Online Conference Pharmaceutical and Medical Sciences: A Response to COVID-19 Theme: Support Healthcare Heroes

Publication Link

https://pmsazhar.conferences.ekb.eg/

Details

Type

Article

Locale

en

Created At

13 Dec 2022