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 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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Exposure to aristolochic acid I compromises the maturational competency of porcine oocytes via oxidative stress-induced DNA damage

Aging ◽

10.18632/aging.101911 ◽

2019 ◽

Vol 11 (8) ◽

pp. 2241-2252 ◽

Cited By ~ 4

Author(s):

Yu Zhang ◽

Xiayan ShiYang ◽

Yuwei Zhang ◽

Yu Li ◽

Xiaoyan Shi ◽

...

Keyword(s):

Oxidative Stress ◽

Dna Damage ◽

Aristolochic Acid ◽

Aristolochic Acid I

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Acute and Subchronic Toxicity Studies of Aristolochic Acid A in Tianfu Broilers

Animals ◽

10.3390/ani11061556 ◽

2021 ◽

Vol 11 (6) ◽

pp. 1556

Author(s):

Dan Xu ◽

Chonglin Ran ◽

Lizi Yin ◽

Juchun Lin ◽

Hualin Fu ◽

...

Keyword(s):

Oxidative Stress ◽

Aristolochic Acid ◽

Lethal Dose ◽

Redox Balance ◽

Toxicity Tests ◽

Economic Losses ◽

Renal Cells ◽

Subchronic Toxicity ◽

Renal Tubular ◽

Toxic Potential

Aristolochic acid (AA) is one of the components of some traditional Chinese medicines, which has high toxic potential in animals, leading to huge economic losses in the breeding industry. The purpose of this study is to evaluate the toxicology of AA on Tianfu broilers through acute and subchronic toxicity tests. The results showed that the median lethal dose of AA to Tianfu broilers was 14.52 mg/kg. After continuous intraperitoneal injection of AA solution (1.452 mg/kg) for 28 days, the swollen and necrotic renal tubular epithelial cells were histologically observed; in addition, blood urea nitrogen (BUN) and creatinine (Cre) were significantly increased, indicating AA could induce serious kidney lesions in broilers. Moreover, the ROS, the apoptosis rate and the depolarization rate of the mitochondrial membrane potential of broilers’ renal cells increased. The results of QRT-PCR showed that AA reduced the mRNA expressions of HO-1, NQO1, Raf-1 and Bcl-2, while the expressions of Bax and Caspase-3 increased, which show that AA aroused oxidative stress and promoted the apoptosis of renal cells. In conclusion, AA has been found to damage broilers’ kidneys by breaking the redox balance to form oxidative stress, along with promoting apoptosis of renal cells.

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Aristolactam I a metabolite of aristolochic acid I upon activation forms an adduct found in DNA of patients with Chinese herbs nephropathy

Experimental and Toxicologic Pathology ◽

10.1016/s0940-2993(99)80033-5 ◽

1999 ◽

Vol 51 (4-5) ◽

pp. 421-427 ◽

Cited By ~ 46

Author(s):

M. Stiborová ◽

E. Frei ◽

A. Breuer ◽

C.A. Bieler ◽

H.H. Schmeiser

Keyword(s):

Aristolochic Acid ◽

Chinese Herbs ◽

Aristolochic Acid I ◽

Chinese Herbs Nephropathy

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Lupane Type Triterpene Isolated from the Leaves of Thecacoris Annobonea (Euphorbiaceae)

JOURNAL OF ADVANCES IN CHEMISTRY ◽

10.24297/jac.v12i10.5519 ◽

2013 ◽

Vol 12 (10) ◽

pp. 695-701

Author(s):

Herve Martial Poumale Poumale ◽

Alphonsine Nkapwa Guedem ◽

Louis Pergaud Sandjo ◽

Bonaventure Tchaleu Ngadjui ◽

Yoshihito Shiono

Keyword(s):

Antimicrobial Activity ◽

Root Growth ◽

Betulinic Acid ◽

Aristolochic Acid ◽

2D Nmr ◽

Aristolochic Acid I

A new lupane type triterpene (1), together with betulinic acid (2), friedelin (3), aristolochic acid I (4), alpinumisoflavone (5) and 4’-O-methylepinumisoflavone (6) have been isolated from the leaves of Thecacoris annobonea. The structure of the new compound was elucidated on the basis of 1 and 2D NMR experiments. The isolated compounds were evaluated for their phytotoxicity and antimicrobial activity. 1 exhibited significant antimicrobial activity at 30 μg/ml and compounds 1, 2, 3, 4, 5 and 6 inhibited root growth lettuce at 100 μg/ml.

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Known Hepatoprotectors Act as Antioxidants and Immune Stimulators in Stressed Mice: Perspectives in Animal Health Care

Current Pharmaceutical Design ◽

10.2174/1381612825666190116151628 ◽

2019 ◽

Vol 24 (40) ◽

pp. 4825-4837 ◽

Cited By ~ 2

Author(s):

Gustavo Alberto de la Riva ◽

Francisco Javier López Mendoza ◽

Guillermin Agüero-Chapin

Keyword(s):

Oxidative Stress ◽

Animal Health ◽

Cellular Damage ◽

Farm Animals ◽

Physiological Status ◽

Stress Markers ◽

Glutathione Peroxidases ◽

Transport Chain ◽

Exogenous Compounds ◽

Relationship Of

Background: Oxygen is involved in a variety of physiological reactions in aerobic organisms, such as those produced in the electron transport chain, hydroxylation, and oxygenation. Reactive oxygen species (ROS) are naturally formed as byproducts from these previously reactions involving the O2 molecule; they are made up of superoxide anion (O2−), hydroxyl radical (HO−), hydrogen peroxide (H2O2), nitric oxide (NO), peroxyl (ROO−), and reactive aldehyde (ROCH). Under certain environmental stress conditions, ROS are accumulated causing cellular damage but also triggering the overexpression of several enzyme classes such as superoxide dismutases (SOD), catalases (CAT) and glutathione peroxidases (GPx), which represent an important intrinsic antioxidant defence line. Liver is a key organ in vertebrates including farm animals and human. The oxidative stress plays an important role in systemic malfunctions including hepatic, renal and immunological, disorders. Methods: This review presents a brief update about the relationship of oxidative stress with hepatic, renal and immunological malfunctions in stressed organisms. Cellular and exogenous hepatoprotective compounds share also the ability to scavenge ROS acting as antioxidants and in many cases as stimulators of immune response in stressed organisms. We present the effect of some hepatoprotectors on the hepatic, renal and immunological function in stressed mice by the jointed evaluation of biological and oxidative stress markers. Conclusion: Hepatoprotective effect of several exogenous compounds is very associated with their antioxidant capacity. This fact is relevant for keeping oxidant/antioxidant balance in the respective organs, but also for maintaining the physiological status of the whole organism.

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Analysis of Polycyclic Aromatic Hydrocarbons and Phthalate Esters in Soil and Food Grains from the Balkan Peninsula: Implication on DNA Adduct Formation by Aristolochic Acid I and Balkan Endemic Nephropathy

Environmental Science & Technology ◽

10.1021/acs.est.1c00648 ◽

2021 ◽

Author(s):

Wanlin Guo ◽

Jiayin Zhang ◽

Zhihan Sun ◽

William H. Orem ◽

Calin A. Tatu ◽

...

Keyword(s):

Aristolochic Acid ◽

Phthalate Esters ◽

Balkan Peninsula ◽

Adduct Formation ◽

Dna Adduct ◽

Balkan Endemic Nephropathy ◽

Food Grains ◽

Polycyclic Aromatic ◽

Endemic Nephropathy ◽

Aristolochic Acid I

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Real-time monitoring of aristolochic acid I reduction process using surface-enhanced Raman Spectroscopy with DFT simulation

Biosensors and Bioelectronics ◽

10.1016/j.bios.2021.113061 ◽

2021 ◽

Vol 179 ◽

pp. 113061

Author(s):

Lu Cao ◽

Hongguang Liu ◽

Wenjun Xie ◽

Shumeng Jiao ◽

Xueqiang Wu ◽

...

Keyword(s):

Raman Spectroscopy ◽

Real Time ◽

Aristolochic Acid ◽

Reduction Process ◽

Surface Enhanced Raman Spectroscopy ◽

Real Time Monitoring ◽

Dft Simulation ◽

Surface Enhanced ◽

Surface Enhanced Raman ◽

Aristolochic Acid I

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Solid-Phase Extraction of Aristolochic Acid I from Natural Plant Using Dual Ionic Liquid-Immobilized ZIF-67 as Sorbent

Separations ◽

10.3390/separations8020022 ◽

2021 ◽

Vol 8 (2) ◽

pp. 22

Author(s):

Pei Chen ◽

Xiaoman Li ◽

Xuemin Yan ◽

Minglei Tian

Keyword(s):

Solid Phase Extraction ◽

Aristolochic Acid ◽

Solid Phase ◽

Phase Extraction ◽

Liquid Adsorption ◽

Successful Separation ◽

Metal Organic ◽

Herbal Plants ◽

Aristolochic Acid I ◽

Herbal Plant

(1) Background: ZIF-67 is one of the most intriguing metal–organic frameworks already applied in liquid adsorption. To increase its adsorption performance, dual ionic liquids were immobilized on ZIF-67 in this research; (2) Methods: The obtained sorbent was used to adsorb aristolochic acid I (AAI) in standard solutions. Then, the sorbent was applied in solid-phase extraction to remove AAI from Fibraurea Recisa Pierre extracted solution. (3) Results: By analyzing the adsorption models, the highest adsorption capacity of immobilized sorbent (50.9 mg/g) was obtained at 25 °C within 120 min. In the SPE process, 0.02 mg of AAI was removed per gram of herbal plant, the adequate recoveries were in the range of 96.2–100.0%, and RSDs were 3.5–4.0%; (4) Conclusions: The provided experimental data revealed that ZIF-67@EIM-MIM was an excellent potential sorbent to adsorb and remove AAI from herbal plant extract, and the successful separation indicated that this sorbent could be an ideal material for the pretreatment of herbal plants containing AAI.

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