Nrf2/HO-1, NF-κB and PI3K/Akt signalling pathways decipher the therapeutic mechanism of pitavastatin in early phase liver fibrosis in rats

verfasst von

Marawan A Elbaset, Bassim M S A Mohamed, Alyaa Hessin, Sahar S Abd El-Rahman, Tuba Esatbeyoglu, Sherif M Afifi, Hany M Fayed

Abstract

Liver fibrosis is a common chronic hepatic disease. This study aimed to investigate the effect of pitavastatin (Pit) against thioacetamide (TAA)-induced liver fibrosis. Rats were divided into four groups: (1) control group; (2) TAA group (100 mg/kg, i.p.) three times weekly for 2 weeks; (3 and 4) TAA/Pit-treated group, in which Pit was administered orally (0.4 and 0.8 mg/kg/day) for 2 weeks following TAA injections. TAA caused liver damage manifested by elevated serum transaminases, reduced albumin and histological alterations. Hepatic malondialdehyde (MDA) was increased, and glutathione (GSH) and superoxide dismutase (SOD) were decreased in TAA-administered rats. TAA upregulated the inflammatory markers NF-κB, NF-κB p65, TNF-α and IL-6. Treatment with Pit ameliorated serum transaminases, elevated serum albumin and prevented histopathological changes in TAA-intoxicated rats. Pit suppressed MDA, NF-κB, NF-κB p65, the inflammatory cytokines and PI3K mRNA in TAA-intoxicated rats. In addition, Pit enhanced hepatic antioxidants and boosted the nuclear factor erythroid 2-related factor 2 (Nrf2) and heme oxygenase-1 (HO-1) mRNA. Moreover, immunohistological studies supported the ability of Pit to reduce liver fibrosis via suppressing p-AKT expression. In conclusion, Pit effectively prevents TAA-induced liver fibrosis by attenuating oxidative stress and the inflammatory response. The hepatoprotective efficacy of Pit was associated with the upregulation of Nrf2/HO-1 and downregulation of NF-κB and PI3K/Akt signalling pathways.

Organisationseinheit(en)

Institut für Lebensmittelwissenschaft und Humanernährung
Molekulare Lebensmittelchemie und -entwicklung

Externe Organisation(en)

Clinical Research Center Cairo (CRC)
Cairo University
University of Sadat City

Typ

Artikel

Journal

Journal of Cellular and Molecular Medicine

Band

28

ISSN

1582-4934

Publikationsdatum

05.02.2024

Publikationsstatus

Veröffentlicht

Peer-reviewed

Ja

ASJC Scopus Sachgebiete

Molekularmedizin, Zellbiologie

Elektronische Version(en)

https://doi.org/10.1111/jcmm.18116 (Zugang: Offen)