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CYP2E1 inhibition and NF_κB Signaling Pathway are Involved in the Protective Molecular Effect of Origanum floribundum against Acetaminophen-induced acute Hepatotoxicity in Rats

The present study aimed to estimate the potential and the molecular mechanism of the hydro-ethanolic extract of O.floribundum against acetaminophen (AC) induced hepatotoxicity. Four groups of female Wistar rats (n=6) was formed to study the hepatoprotective effect of O.floribundum extract against ac...

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Autores principales: Khelfallah, Amina, Aouay, Bakhta, Kebieche, Mohamed, Fetoui, Hamadi
Formato: Online Artículo Texto
Lenguaje:English
Publicado: Shaheed Beheshti University of Medical Sciences 2021
Materias:
Acceso en línea:https://www.ncbi.nlm.nih.gov/pmc/articles/PMC8653642/
https://www.ncbi.nlm.nih.gov/pubmed/34904010
http://dx.doi.org/10.22037/ijpr.2021.114487.14878
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author Khelfallah, Amina
Aouay, Bakhta
Kebieche, Mohamed
Fetoui, Hamadi
author_facet Khelfallah, Amina
Aouay, Bakhta
Kebieche, Mohamed
Fetoui, Hamadi
author_sort Khelfallah, Amina
collection PubMed
description The present study aimed to estimate the potential and the molecular mechanism of the hydro-ethanolic extract of O.floribundum against acetaminophen (AC) induced hepatotoxicity. Four groups of female Wistar rats (n=6) was formed to study the hepatoprotective effect of O.floribundum extract against acetaminophen overdose (2 g/kg): Groups N and AC received orally tap water for 03 days and Groups O. floribundum + AC and N+O.floribundum: received orally O. floribundum extract (400 mg/kg). After 1hour (h) of the last dose administered, the paracetamol solution (2 g/kg) is administered orally for group AC and O. floribundum + AC. The hydroethanolic extract of O. floribundum shows strong antioxidant activity “in-vitro”. After 24 h, a single dose of acetaminophen increased significantly serum aspartate aminotransferase (AST), alanine aminotransferase (ALT) and the activity of alkaline phosphatase (ALP) significantly and decreased total protein and albumin levels compared to the normal group. These alterations are confirmed by histological observations with inflammation markers (congestion, inflammatory cells infiltration). These observed effects are mainly due to the over-expression of the CYP2E1 and NF_κB genes marked in this study by quantitative RT-PCR. Also, acetaminophen overdose leads to activation of the mitochondrial permeability transition (MPT). leading to hepatocyte necrosis. Pretreatment with O.floribundum before acetaminophen administration removes all previously observed biochemical, histological. and mitochondrial manifestations. These results suggest that O.floribundum has a potent antioxidant power and an interesting hepatoprotective activity against acetaminophen toxicity partly due to the inhibition of CYP2E1 and NF_κB genes expression.
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spelling pubmed-86536422021-12-12 CYP2E1 inhibition and NF_κB Signaling Pathway are Involved in the Protective Molecular Effect of Origanum floribundum against Acetaminophen-induced acute Hepatotoxicity in Rats Khelfallah, Amina Aouay, Bakhta Kebieche, Mohamed Fetoui, Hamadi Iran J Pharm Res Original Article The present study aimed to estimate the potential and the molecular mechanism of the hydro-ethanolic extract of O.floribundum against acetaminophen (AC) induced hepatotoxicity. Four groups of female Wistar rats (n=6) was formed to study the hepatoprotective effect of O.floribundum extract against acetaminophen overdose (2 g/kg): Groups N and AC received orally tap water for 03 days and Groups O. floribundum + AC and N+O.floribundum: received orally O. floribundum extract (400 mg/kg). After 1hour (h) of the last dose administered, the paracetamol solution (2 g/kg) is administered orally for group AC and O. floribundum + AC. The hydroethanolic extract of O. floribundum shows strong antioxidant activity “in-vitro”. After 24 h, a single dose of acetaminophen increased significantly serum aspartate aminotransferase (AST), alanine aminotransferase (ALT) and the activity of alkaline phosphatase (ALP) significantly and decreased total protein and albumin levels compared to the normal group. These alterations are confirmed by histological observations with inflammation markers (congestion, inflammatory cells infiltration). These observed effects are mainly due to the over-expression of the CYP2E1 and NF_κB genes marked in this study by quantitative RT-PCR. Also, acetaminophen overdose leads to activation of the mitochondrial permeability transition (MPT). leading to hepatocyte necrosis. Pretreatment with O.floribundum before acetaminophen administration removes all previously observed biochemical, histological. and mitochondrial manifestations. These results suggest that O.floribundum has a potent antioxidant power and an interesting hepatoprotective activity against acetaminophen toxicity partly due to the inhibition of CYP2E1 and NF_κB genes expression. Shaheed Beheshti University of Medical Sciences 2021 /pmc/articles/PMC8653642/ /pubmed/34904010 http://dx.doi.org/10.22037/ijpr.2021.114487.14878 Text en https://creativecommons.org/licenses/by/3.0/This is an Open Access article distributed under the terms of the Creative Commons Attribution License, (http://creativecommons.org/licenses/by/3.0/ (https://creativecommons.org/licenses/by/3.0/) ) which permits unrestricted use, distribution, and reproduction in any medium, provided the original work is properly cited.
spellingShingle Original Article
Khelfallah, Amina
Aouay, Bakhta
Kebieche, Mohamed
Fetoui, Hamadi
CYP2E1 inhibition and NF_κB Signaling Pathway are Involved in the Protective Molecular Effect of Origanum floribundum against Acetaminophen-induced acute Hepatotoxicity in Rats
title CYP2E1 inhibition and NF_κB Signaling Pathway are Involved in the Protective Molecular Effect of Origanum floribundum against Acetaminophen-induced acute Hepatotoxicity in Rats
title_full CYP2E1 inhibition and NF_κB Signaling Pathway are Involved in the Protective Molecular Effect of Origanum floribundum against Acetaminophen-induced acute Hepatotoxicity in Rats
title_fullStr CYP2E1 inhibition and NF_κB Signaling Pathway are Involved in the Protective Molecular Effect of Origanum floribundum against Acetaminophen-induced acute Hepatotoxicity in Rats
title_full_unstemmed CYP2E1 inhibition and NF_κB Signaling Pathway are Involved in the Protective Molecular Effect of Origanum floribundum against Acetaminophen-induced acute Hepatotoxicity in Rats
title_short CYP2E1 inhibition and NF_κB Signaling Pathway are Involved in the Protective Molecular Effect of Origanum floribundum against Acetaminophen-induced acute Hepatotoxicity in Rats
title_sort cyp2e1 inhibition and nf_κb signaling pathway are involved in the protective molecular effect of origanum floribundum against acetaminophen-induced acute hepatotoxicity in rats
topic Original Article
url https://www.ncbi.nlm.nih.gov/pmc/articles/PMC8653642/
https://www.ncbi.nlm.nih.gov/pubmed/34904010
http://dx.doi.org/10.22037/ijpr.2021.114487.14878
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