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)

BibTeX

@article{17af3b8f80a04be7a00d2609275417db,
title = "Nrf2/HO-1, NF-κB and PI3K/Akt signalling pathways decipher the therapeutic mechanism of pitavastatin in early phase liver fibrosis in rats",
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.",
keywords = "NF-κB, PI3k, Nrf2, fibrosis, oxidative stress, signalling pathway, statin",
author = "Elbaset, {Marawan A} and Mohamed, {Bassim M S A} and Alyaa Hessin and {Abd El-Rahman}, {Sahar S} and Tuba Esatbeyoglu and Afifi, {Sherif M} and Fayed, {Hany M}",
note = "Funding Information: The publication of this article was funded by the Open Access Fund of Leibniz Universit{\"a}t Hannover.",
year = "2024",
month = feb,
day = "5",
doi = "10.1111/jcmm.18116",
language = "English",
volume = "28",
journal = "Journal of Cellular and Molecular Medicine",
issn = "1582-4934",
publisher = "Wiley-Blackwell Publishing Ltd",
number = "3",
}