Aristolochic Acid I-Induced Hepatotoxicity in Tianfu Broilers Is Associated with Oxidative-Stress-Mediated Apoptosis and Mitochondrial Damage

Aristolochic acid (AA) is a component of traditional Chinese herbs and commonly used for farm animals in China. Over-exposure of AA has been proven to be associated with hepatotoxicity; however, the mechanism of action of AA-I-induced hepatotoxicity remains unknown. In the current study, a subchroni...

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Main Authors: Dan Xu, Lizi Yin, Juchun Lin, Hualin Fu, Xi Peng, Lijen Chang, Yilei Zheng, Xiaoling Zhao, Gang Shu
Format: Article
Language:English
Published: MDPI AG 2021-12-01
Series:Animals
Subjects:
Online Access:https://www.mdpi.com/2076-2615/11/12/3437
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author Dan Xu
Lizi Yin
Juchun Lin
Hualin Fu
Xi Peng
Lijen Chang
Yilei Zheng
Xiaoling Zhao
Gang Shu
author_facet Dan Xu
Lizi Yin
Juchun Lin
Hualin Fu
Xi Peng
Lijen Chang
Yilei Zheng
Xiaoling Zhao
Gang Shu
author_sort Dan Xu
collection DOAJ
description Aristolochic acid (AA) is a component of traditional Chinese herbs and commonly used for farm animals in China. Over-exposure of AA has been proven to be associated with hepatotoxicity; however, the mechanism of action of AA-I-induced hepatotoxicity remains unknown. In the current study, a subchronic toxicity test was conducted to evaluate the mechanism of AA-induced hepatotoxicity in Tianfu broilers. According to the results, AA-I-induced hepatotoxicity in Tianfu broilers was evidenced by the elevation of liver weight, levels of serum glutamic oxalacetic transaminase (GOT) and glutamic-pyruvic transaminase (GPT). Furthermore, hepatocyte swelling, vesicular degeneration and steatosis were observed. Additionally, AA-I elevated the production of reactive oxygen species (ROS) and induced oxidative stress, which further led to excessive apoptosis, characterized by mitochondrial depolarization, upregulation of Bax, and down-regulation of Bcl-2 expression. In conclusion, the mechanism of AA-I-induced hepatotoxicity was associated with oxidative-stress-mediated apoptosis and mitochondrial damage.
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spelling doaj.art-469affef3c2144e7bcaf8384e03c349c2023-11-23T03:26:56ZengMDPI AGAnimals2076-26152021-12-011112343710.3390/ani11123437Aristolochic Acid I-Induced Hepatotoxicity in Tianfu Broilers Is Associated with Oxidative-Stress-Mediated Apoptosis and Mitochondrial DamageDan Xu0Lizi Yin1Juchun Lin2Hualin Fu3Xi Peng4Lijen Chang5Yilei Zheng6Xiaoling Zhao7Gang Shu8Farm Animal Genetic Resources Exploration and Innovation Key Laboratory of Sichuan Province, Sichuan Agricultural University, Chengdu 611130, ChinaDepartment of Basic Veterinary Medicine, Sichuan Agricultural University, Chengdu 611130, ChinaDepartment of Basic Veterinary Medicine, Sichuan Agricultural University, Chengdu 611130, ChinaDepartment of Basic Veterinary Medicine, Sichuan Agricultural University, Chengdu 611130, ChinaSichuan Industrial Institute of Antibiotics, Chengdu University, Chengdu 611130, ChinaDepartment of Veterinary Clinical Science, College of Veterinary Medicine, Oklahoma State University, Stillwater, OK 74078, USACollege of Veterinary Medicine, University of Minnesota, Minneapolis, MN 55791, USAFarm Animal Genetic Resources Exploration and Innovation Key Laboratory of Sichuan Province, Sichuan Agricultural University, Chengdu 611130, ChinaDepartment of Basic Veterinary Medicine, Sichuan Agricultural University, Chengdu 611130, ChinaAristolochic acid (AA) is a component of traditional Chinese herbs and commonly used for farm animals in China. Over-exposure of AA has been proven to be associated with hepatotoxicity; however, the mechanism of action of AA-I-induced hepatotoxicity remains unknown. In the current study, a subchronic toxicity test was conducted to evaluate the mechanism of AA-induced hepatotoxicity in Tianfu broilers. According to the results, AA-I-induced hepatotoxicity in Tianfu broilers was evidenced by the elevation of liver weight, levels of serum glutamic oxalacetic transaminase (GOT) and glutamic-pyruvic transaminase (GPT). Furthermore, hepatocyte swelling, vesicular degeneration and steatosis were observed. Additionally, AA-I elevated the production of reactive oxygen species (ROS) and induced oxidative stress, which further led to excessive apoptosis, characterized by mitochondrial depolarization, upregulation of Bax, and down-regulation of Bcl-2 expression. In conclusion, the mechanism of AA-I-induced hepatotoxicity was associated with oxidative-stress-mediated apoptosis and mitochondrial damage.https://www.mdpi.com/2076-2615/11/12/3437aristolochic acidliveroxidative stressapoptosismitochondria
spellingShingle Dan Xu
Lizi Yin
Juchun Lin
Hualin Fu
Xi Peng
Lijen Chang
Yilei Zheng
Xiaoling Zhao
Gang Shu
Aristolochic Acid I-Induced Hepatotoxicity in Tianfu Broilers Is Associated with Oxidative-Stress-Mediated Apoptosis and Mitochondrial Damage
Animals
aristolochic acid
liver
oxidative stress
apoptosis
mitochondria
title Aristolochic Acid I-Induced Hepatotoxicity in Tianfu Broilers Is Associated with Oxidative-Stress-Mediated Apoptosis and Mitochondrial Damage
title_full Aristolochic Acid I-Induced Hepatotoxicity in Tianfu Broilers Is Associated with Oxidative-Stress-Mediated Apoptosis and Mitochondrial Damage
title_fullStr Aristolochic Acid I-Induced Hepatotoxicity in Tianfu Broilers Is Associated with Oxidative-Stress-Mediated Apoptosis and Mitochondrial Damage
title_full_unstemmed Aristolochic Acid I-Induced Hepatotoxicity in Tianfu Broilers Is Associated with Oxidative-Stress-Mediated Apoptosis and Mitochondrial Damage
title_short Aristolochic Acid I-Induced Hepatotoxicity in Tianfu Broilers Is Associated with Oxidative-Stress-Mediated Apoptosis and Mitochondrial Damage
title_sort aristolochic acid i induced hepatotoxicity in tianfu broilers is associated with oxidative stress mediated apoptosis and mitochondrial damage
topic aristolochic acid
liver
oxidative stress
apoptosis
mitochondria
url https://www.mdpi.com/2076-2615/11/12/3437
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