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

authored by

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.

Organisation(s)

Institute of Food Science and Human Nutrition
Molecular Food Chemistry and Food Development

External Organisation(s)

Medical Research and Clinical Studies Institute
Cairo University
University of Sadat City

Type

Article

Journal

Journal of Cellular and Molecular Medicine

Volume

28

ISSN

1582-4934

Publication date

05.02.2024

Publication status

Published

Peer reviewed

Yes

ASJC Scopus subject areas

Molecular Medicine, Cell Biology

Electronic version(s)

https://doi.org/10.1111/jcmm.18116 (Access: Open)