Saffron offers hepatoprotection via up-regulation of hepatic farnesoid-X-activated receptors in a rat model of acetaminophen-induced hepatotoxicity

Objectives: The most important toxicity of acetaminophen is hepatotoxicity. Farnesoid X-activated receptors (FXR) are one of the nuclear receptor superfamily members which have a pivotal role in the bile acid regulation. The objective of the present study was to examine the role of FXR in mediating...

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Main Authors: Vahid Jamshidi, Seyed Ali Hashemi, azadeh Khalili, Parviz Fallah, Mohammad Mahdi Ahmadian-Attari, Leila Beikzadeh, Roham Mazloom, Parvaneh Najafizadeh, Gholamreza Bayat
Format: Article
Language:English
Published: Mashhad University of Medical Sciences 2021-11-01
Series:Avicenna Journal of Phytomedicine
Subjects:
Online Access:https://ajp.mums.ac.ir/article_18227_a040a3498c9370831602f25abe1dd88b.pdf
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author Vahid Jamshidi
Seyed Ali Hashemi
azadeh Khalili
Parviz Fallah
Mohammad Mahdi Ahmadian-Attari
Leila Beikzadeh
Roham Mazloom
Parvaneh Najafizadeh
Gholamreza Bayat
author_facet Vahid Jamshidi
Seyed Ali Hashemi
azadeh Khalili
Parviz Fallah
Mohammad Mahdi Ahmadian-Attari
Leila Beikzadeh
Roham Mazloom
Parvaneh Najafizadeh
Gholamreza Bayat
author_sort Vahid Jamshidi
collection DOAJ
description Objectives: The most important toxicity of acetaminophen is hepatotoxicity. Farnesoid X-activated receptors (FXR) are one of the nuclear receptor superfamily members which have a pivotal role in the bile acid regulation. The objective of the present study was to examine the role of FXR in mediating the hepatoprotective effects of saffron.Methods: Male Wister rats were randomly allocated into five groups including a control, vehicle, acetaminophen and two saffron extract groups of 150 and 300 mg/kg/day. The liver function and hepatic FXR expression were evaluated using biochemical assay and real time RT-PCR, respectively. Data analysis was performed using the one-way ANOVA followed by Duncan's multiple range test.Results: Levels of aspartate aminotransferase (AST), alanine aminotransferase (ALT), alkaline phosphatase (ALP) and lactate dehydrogenase (LDH) of the acetaminophen group were significantly higher than the control group whereas those of the extract-treated groups were significantly lower than those of the acetaminophen group. The real time RT-PCR findings showed a non-significant down-regulation of FXR mRNA expression, however, a dose-dependent FXR up-regulation was seen in the groups treated with 150 and 300 mg/kg of the extract for 2.67 (p=0.002) and 10.22 (p=0.0001) fold, respectively.Conclusion: The main finding of the present study was that the hepatic FXR up-regulation had an important role in saffron hepatoprotective activity.
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spelling doaj.art-79c334dcbd39488dbd4d155356bf461a2022-12-21T21:30:12ZengMashhad University of Medical SciencesAvicenna Journal of Phytomedicine2228-79302228-79492021-11-0111662263210.22038/ajp.2021.1822718227Saffron offers hepatoprotection via up-regulation of hepatic farnesoid-X-activated receptors in a rat model of acetaminophen-induced hepatotoxicityVahid Jamshidi0Seyed Ali Hashemi1azadeh Khalili2Parviz Fallah3Mohammad Mahdi Ahmadian-Attari4Leila Beikzadeh5Roham Mazloom6Parvaneh Najafizadeh7Gholamreza Bayat8Department of Pharmacology and Toxicology, Faculty of Pharmacy, Pharmaceutical Sciences Branch, Islamic Azad University, Tehran, IranDepartment of Pathology, School of Medicine, Alborz University of Medical Sciences, Karaj,IranDepartment of Physiology-Pharmacology-Medical Physic, School of Medicine, Alborz University of Medical Sciences, Karaj, Iran Evidence-based Phytotherapy and Complementary Medicine Research Center, Alborz University of Medical Sciences, Karaj, IranDepartment of Medical Laboratory Sciences, Faculty of Para-Medicine; Alborz University of Medical SciencesDepartment of Pharmacognosy, Faculty of Pharmacy, Alborz University of Medical Sciences, Karaj,Iran Evidence-based Phytotherapy and Complementary Medicine Research Center, Alborz University of Medical Sciences, Karaj, IranDepartment of Medical Laboratory Sciences, Faculty of Para-Medicine, Alborz University of Medical Sciences, Karaj, IranDepartment of Physiology-Pharmacology-Medical Physic, School of Medicine, Alborz University of Medical Sciences, Karaj, IranDepartment of Pharmacology and Toxicology, Faculty of Pharmacy, Pharmaceutical Sciences Branch, Islamic Azad University, Tehran, Iran Department of Pharmacology, School of Medicine, Iran University of Medical Sciences, Tehran, IranDepartment of Physiology-Pharmacology-Medical Physic, School of Medicine, Alborz University of Medical Sciences, Karaj, IranObjectives: The most important toxicity of acetaminophen is hepatotoxicity. Farnesoid X-activated receptors (FXR) are one of the nuclear receptor superfamily members which have a pivotal role in the bile acid regulation. The objective of the present study was to examine the role of FXR in mediating the hepatoprotective effects of saffron.Methods: Male Wister rats were randomly allocated into five groups including a control, vehicle, acetaminophen and two saffron extract groups of 150 and 300 mg/kg/day. The liver function and hepatic FXR expression were evaluated using biochemical assay and real time RT-PCR, respectively. Data analysis was performed using the one-way ANOVA followed by Duncan's multiple range test.Results: Levels of aspartate aminotransferase (AST), alanine aminotransferase (ALT), alkaline phosphatase (ALP) and lactate dehydrogenase (LDH) of the acetaminophen group were significantly higher than the control group whereas those of the extract-treated groups were significantly lower than those of the acetaminophen group. The real time RT-PCR findings showed a non-significant down-regulation of FXR mRNA expression, however, a dose-dependent FXR up-regulation was seen in the groups treated with 150 and 300 mg/kg of the extract for 2.67 (p=0.002) and 10.22 (p=0.0001) fold, respectively.Conclusion: The main finding of the present study was that the hepatic FXR up-regulation had an important role in saffron hepatoprotective activity.https://ajp.mums.ac.ir/article_18227_a040a3498c9370831602f25abe1dd88b.pdffarnesoid x-activated receptoracetaminophencrocus sativuscrocintoxicity
spellingShingle Vahid Jamshidi
Seyed Ali Hashemi
azadeh Khalili
Parviz Fallah
Mohammad Mahdi Ahmadian-Attari
Leila Beikzadeh
Roham Mazloom
Parvaneh Najafizadeh
Gholamreza Bayat
Saffron offers hepatoprotection via up-regulation of hepatic farnesoid-X-activated receptors in a rat model of acetaminophen-induced hepatotoxicity
Avicenna Journal of Phytomedicine
farnesoid x-activated receptor
acetaminophen
crocus sativus
crocin
toxicity
title Saffron offers hepatoprotection via up-regulation of hepatic farnesoid-X-activated receptors in a rat model of acetaminophen-induced hepatotoxicity
title_full Saffron offers hepatoprotection via up-regulation of hepatic farnesoid-X-activated receptors in a rat model of acetaminophen-induced hepatotoxicity
title_fullStr Saffron offers hepatoprotection via up-regulation of hepatic farnesoid-X-activated receptors in a rat model of acetaminophen-induced hepatotoxicity
title_full_unstemmed Saffron offers hepatoprotection via up-regulation of hepatic farnesoid-X-activated receptors in a rat model of acetaminophen-induced hepatotoxicity
title_short Saffron offers hepatoprotection via up-regulation of hepatic farnesoid-X-activated receptors in a rat model of acetaminophen-induced hepatotoxicity
title_sort saffron offers hepatoprotection via up regulation of hepatic farnesoid x activated receptors in a rat model of acetaminophen induced hepatotoxicity
topic farnesoid x-activated receptor
acetaminophen
crocus sativus
crocin
toxicity
url https://ajp.mums.ac.ir/article_18227_a040a3498c9370831602f25abe1dd88b.pdf
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