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

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Authors

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

External Research Organisations

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

Original languageEnglish
Article numbere18116
JournalJournal of Cellular and Molecular Medicine
Volume28
Issue number3
Publication statusPublished - 5 Feb 2024

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

ASJC Scopus subject areas

Cite this

Nrf2/HO-1, NF-κB and PI3K/Akt signalling pathways decipher the therapeutic mechanism of pitavastatin in early phase liver fibrosis in rats. / Elbaset, Marawan A; Mohamed, Bassim M S A; Hessin, Alyaa et al.
In: Journal of Cellular and Molecular Medicine, Vol. 28, No. 3, e18116, 05.02.2024.

Research output: Contribution to journalArticleResearchpeer review

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@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.",
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TY - JOUR

T1 - Nrf2/HO-1, NF-κB and PI3K/Akt signalling pathways decipher the therapeutic mechanism of pitavastatin in early phase liver fibrosis in rats

AU - Elbaset, Marawan A

AU - Mohamed, Bassim M S A

AU - Hessin, Alyaa

AU - Abd El-Rahman, Sahar S

AU - Esatbeyoglu, Tuba

AU - Afifi, Sherif M

AU - Fayed, Hany M

N1 - Funding Information: The publication of this article was funded by the Open Access Fund of Leibniz Universität Hannover.

PY - 2024/2/5

Y1 - 2024/2/5

N2 - 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.

AB - 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.

KW - NF-κB

KW - PI3k, Nrf2

KW - fibrosis

KW - oxidative stress

KW - signalling pathway

KW - statin

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U2 - 10.1111/jcmm.18116

DO - 10.1111/jcmm.18116

M3 - Article

C2 - 38214394

VL - 28

JO - Journal of Cellular and Molecular Medicine

JF - Journal of Cellular and Molecular Medicine

SN - 1582-4934

IS - 3

M1 - e18116

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