Taraxasterol alleviates aflatoxin B1-induced liver damage in broiler chickens via regulation of oxidative stress, apoptosis and autophagy

Aflatoxin B1 (AFB1) is the most dangerous and abundant mycotoxin, which is toxic to almost all animals, and poultry is more sensitive to AFB1 toxicity. Ingesting AFB1-contaminated feed can cause significant liver damage and brings serious harm to poultry, which greatly restricts the development of t...

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Main Authors: Rui Sang, Bingjie Ge, Haifeng Li, Hongyuan Zhou, Kexin Yan, Wei Wang, Qichao Cui, Xuemei Zhang
Format: Article
Language:English
Published: Elsevier 2023-02-01
Series:Ecotoxicology and Environmental Safety
Subjects:
Online Access:http://www.sciencedirect.com/science/article/pii/S0147651323000507
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author Rui Sang
Bingjie Ge
Haifeng Li
Hongyuan Zhou
Kexin Yan
Wei Wang
Qichao Cui
Xuemei Zhang
author_facet Rui Sang
Bingjie Ge
Haifeng Li
Hongyuan Zhou
Kexin Yan
Wei Wang
Qichao Cui
Xuemei Zhang
author_sort Rui Sang
collection DOAJ
description Aflatoxin B1 (AFB1) is the most dangerous and abundant mycotoxin, which is toxic to almost all animals, and poultry is more sensitive to AFB1 toxicity. Ingesting AFB1-contaminated feed can cause significant liver damage and brings serious harm to poultry, which greatly restricts the development of the poultry industry. The present research was implemented to explore the intervention effect and its mechanism of taraxasterol on liver damage induced by AFB1 in broiler chickens. The liver damage model in broiler chickens was established by feeding 0.5 mg/kg AFB1 feed, and taraxasterol (25, 50 and 100 mg/kg BW, respectively) was given in the drinking water for 21 days. The growth performance, liver function, oxidative stress, apoptosis and autophagy were evaluated. The results showed that taraxasterol increased BW and reduced feed-to-gain ratio of broiler chickens induced by AFB1. Taraxasterol improved the levels of serum alanine aminotransferase (ALT), aspartate aminotransferase (AST), γ-glutamyltransferase (GGT), total bilirubin (TBIL) and alkaline phosphatase (ALP), and attenuated hepatic histopathological changes induced by AFB1. Meantime, taraxasterol down-regulated cytochrome P450 (CYP450) enzyme system CYP1A1 and CYP2A6 mRNA expression, inhibited the overproduction of reactive oxygen species (ROS) and malondialdehyde (MDA), and enhanced the activities of antioxidant enzymes glutathione (GSH) and catalase (CAT) and the content of antioxidant superoxide dismutase (SOD) of the liver in broiler chickens induced by AFB1. Furthermore, taraxasterol up-regulated the mRNA and protein expression of hepatic nuclear factor E2 related factor 2 (Nrf2), heme oxygenase 1 (HO-1) and NAD(P)H: quinone oxidoreductase 1 (NQO1), and down-regulated the expression of hepatic kelch like ECH associated protein 1 (Keap1) induced by AFB1 in Keap1/Nrf2 signaling pathway. The ultrastructural observation and RT-qPCR results found that taraxasterol inhibited apoptosis of hepatocytes, up-regulated the expression of B-cell lymphoma-2 (Bcl-2) mRNA and down-regulated the expression of Bax and caspase3 mRNA. Further, taraxasterol restored the autophagy of hepatocytes and down-regulated the mRNA expression of phosphatidylinositol 3-kinase K (PI3K), protein kinase B (AKT) and mammalian target of rapamycin (mTOR) in AFB1-induced liver of broiler chickens. The above results indicate that taraxasterol alleviates liver damage induced by AFB1 in broiler chickens through regulation of Keap1/Nrf2 signaling pathway to exert its antioxidant effect, mitochondrial apoptosis pathway to improve anti-apoptotic ability and PI3K/AKT/mTOR pathway to restore autophagy.
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spelling doaj.art-9510a01c58ee489d882552bc760657912023-02-02T04:47:03ZengElsevierEcotoxicology and Environmental Safety0147-65132023-02-01251114546Taraxasterol alleviates aflatoxin B1-induced liver damage in broiler chickens via regulation of oxidative stress, apoptosis and autophagyRui Sang0Bingjie Ge1Haifeng Li2Hongyuan Zhou3Kexin Yan4Wei Wang5Qichao Cui6Xuemei Zhang7Agricultural College of Yanbian University, Gongyuan Street, Yanji, Jilin 133002, PR ChinaAgricultural College of Yanbian University, Gongyuan Street, Yanji, Jilin 133002, PR ChinaAgricultural College of Yanbian University, Gongyuan Street, Yanji, Jilin 133002, PR ChinaAgricultural College of Yanbian University, Gongyuan Street, Yanji, Jilin 133002, PR ChinaAgricultural College of Yanbian University, Gongyuan Street, Yanji, Jilin 133002, PR ChinaAgricultural College of Yanbian University, Gongyuan Street, Yanji, Jilin 133002, PR ChinaAgricultural College of Yanbian University, Gongyuan Street, Yanji, Jilin 133002, PR ChinaCorresponding author.; Agricultural College of Yanbian University, Gongyuan Street, Yanji, Jilin 133002, PR ChinaAflatoxin B1 (AFB1) is the most dangerous and abundant mycotoxin, which is toxic to almost all animals, and poultry is more sensitive to AFB1 toxicity. Ingesting AFB1-contaminated feed can cause significant liver damage and brings serious harm to poultry, which greatly restricts the development of the poultry industry. The present research was implemented to explore the intervention effect and its mechanism of taraxasterol on liver damage induced by AFB1 in broiler chickens. The liver damage model in broiler chickens was established by feeding 0.5 mg/kg AFB1 feed, and taraxasterol (25, 50 and 100 mg/kg BW, respectively) was given in the drinking water for 21 days. The growth performance, liver function, oxidative stress, apoptosis and autophagy were evaluated. The results showed that taraxasterol increased BW and reduced feed-to-gain ratio of broiler chickens induced by AFB1. Taraxasterol improved the levels of serum alanine aminotransferase (ALT), aspartate aminotransferase (AST), γ-glutamyltransferase (GGT), total bilirubin (TBIL) and alkaline phosphatase (ALP), and attenuated hepatic histopathological changes induced by AFB1. Meantime, taraxasterol down-regulated cytochrome P450 (CYP450) enzyme system CYP1A1 and CYP2A6 mRNA expression, inhibited the overproduction of reactive oxygen species (ROS) and malondialdehyde (MDA), and enhanced the activities of antioxidant enzymes glutathione (GSH) and catalase (CAT) and the content of antioxidant superoxide dismutase (SOD) of the liver in broiler chickens induced by AFB1. Furthermore, taraxasterol up-regulated the mRNA and protein expression of hepatic nuclear factor E2 related factor 2 (Nrf2), heme oxygenase 1 (HO-1) and NAD(P)H: quinone oxidoreductase 1 (NQO1), and down-regulated the expression of hepatic kelch like ECH associated protein 1 (Keap1) induced by AFB1 in Keap1/Nrf2 signaling pathway. The ultrastructural observation and RT-qPCR results found that taraxasterol inhibited apoptosis of hepatocytes, up-regulated the expression of B-cell lymphoma-2 (Bcl-2) mRNA and down-regulated the expression of Bax and caspase3 mRNA. Further, taraxasterol restored the autophagy of hepatocytes and down-regulated the mRNA expression of phosphatidylinositol 3-kinase K (PI3K), protein kinase B (AKT) and mammalian target of rapamycin (mTOR) in AFB1-induced liver of broiler chickens. The above results indicate that taraxasterol alleviates liver damage induced by AFB1 in broiler chickens through regulation of Keap1/Nrf2 signaling pathway to exert its antioxidant effect, mitochondrial apoptosis pathway to improve anti-apoptotic ability and PI3K/AKT/mTOR pathway to restore autophagy.http://www.sciencedirect.com/science/article/pii/S0147651323000507TaraxasterolAflatoxin B1Broiler chickensLiver damageOxidative stress
spellingShingle Rui Sang
Bingjie Ge
Haifeng Li
Hongyuan Zhou
Kexin Yan
Wei Wang
Qichao Cui
Xuemei Zhang
Taraxasterol alleviates aflatoxin B1-induced liver damage in broiler chickens via regulation of oxidative stress, apoptosis and autophagy
Ecotoxicology and Environmental Safety
Taraxasterol
Aflatoxin B1
Broiler chickens
Liver damage
Oxidative stress
title Taraxasterol alleviates aflatoxin B1-induced liver damage in broiler chickens via regulation of oxidative stress, apoptosis and autophagy
title_full Taraxasterol alleviates aflatoxin B1-induced liver damage in broiler chickens via regulation of oxidative stress, apoptosis and autophagy
title_fullStr Taraxasterol alleviates aflatoxin B1-induced liver damage in broiler chickens via regulation of oxidative stress, apoptosis and autophagy
title_full_unstemmed Taraxasterol alleviates aflatoxin B1-induced liver damage in broiler chickens via regulation of oxidative stress, apoptosis and autophagy
title_short Taraxasterol alleviates aflatoxin B1-induced liver damage in broiler chickens via regulation of oxidative stress, apoptosis and autophagy
title_sort taraxasterol alleviates aflatoxin b1 induced liver damage in broiler chickens via regulation of oxidative stress apoptosis and autophagy
topic Taraxasterol
Aflatoxin B1
Broiler chickens
Liver damage
Oxidative stress
url http://www.sciencedirect.com/science/article/pii/S0147651323000507
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