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

Animals ◽  
2021 ◽  
Vol 11 (6) ◽  
pp. 1556
Author(s):  
Dan Xu ◽  
Chonglin Ran ◽  
Lizi Yin ◽  
Juchun Lin ◽  
Hualin Fu ◽  
...  

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.

Animals ◽  
2021 ◽  
Vol 11 (12) ◽  
pp. 3437
Author(s):  
Dan Xu ◽  
Lizi Yin ◽  
Juchun Lin ◽  
Hualin Fu ◽  
Xi Peng ◽  
...  

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.


2015 ◽  
Vol 12 (4) ◽  
pp. 6086-6092 ◽  
Author(s):  
TSAI-KUN WU ◽  
CHYOU-WEI WEI ◽  
YING-RU PAN ◽  
SHUR-HUEIH CHERNG ◽  
WEI-JUNG CHANG ◽  
...  

2019 ◽  
Vol 21 (1) ◽  
pp. 98
Author(s):  
Bintong Yang ◽  
Haichao Song ◽  
Dingjie An ◽  
Dongxing Zhang ◽  
Sayed Haidar Abbas Raza ◽  
...  

Aeromonas veronii is one of the main pathogens causing freshwater fish sepsis and ulcer syndrome. This bacterium has caused serious economic losses in the aquaculture industry worldwide, and it has become an important zoonotic and aquatic agent. However, little is known about the molecular mechanism of pathogenesis of A. veronii. In this study, we first constructed an unmarked mutant strain (ΔpreA) by generating an in-frame deletion of the preA gene, which encodes a periplasmic binding protein, to investigate its role in A. veronii TH0426. Our results showed that the motility and biofilm formation ability of ΔpreA were similar to those of the wild-type strain. However, the adhesion and invasion ability in epithelioma papulosum cyprini (EPC) cells were significantly enhanced (2.0-fold). Furthermore, the median lethal dose (LD50) of ΔpreA was 7.6-fold higher than that of the wild-type strain, which illustrates that the virulence of the mutant was significantly enhanced. This finding is also supported by the cytotoxicity test results, which showed that the toxicity of ΔpreA to EPC cells was enhanced 1.3-fold relative to the wild type. Conversely, tolerance test results showed that oxidative stress resistance of ΔpreA decreased 5.9-fold compared to with the wild-type strain. The results suggest that preA may negatively regulate the virulence of A. veronii TH0426 through the regulation of resistance to oxidative stress. These insights will help to further elucidate the function of preA and understand the pathogenesis of A. veronii.


2014 ◽  
Vol 2014 ◽  
pp. 1-6 ◽  
Author(s):  
Marta Bartoskova ◽  
Radka Dobsikova ◽  
Vlasta Stancova ◽  
Ondrej Pana ◽  
Dana Zivna ◽  
...  

The aim of the study was to investigate the effects of subchronic exposure of zebrafish (Danio rerio) to a fluoroquinolone norfloxacin, using selected oxidative stress parameters as a target. Toxicity tests were performed on zebrafish according to the OECD Guidelines number 203 and number 215. In the Subchronic Toxicity Test, a significant (P<0.01) increase in the activity of glutathione peroxidase, glutathione S-transferase, and catalase was found. In the test, norfloxacin did not affect lipid peroxidation and catalytic activity of glutathione reductase. From the results, we can conclude that norfloxacin has a negative impact on specific biochemical processes connected with the production of reactive oxygen species in fish tested.


2010 ◽  
Vol 30 (1) ◽  
pp. 63-70 ◽  
Author(s):  
Ravirajsinh N Jadeja ◽  
Menaka C Thounaojam ◽  
Ansarullah ◽  
Snehal V Jadav ◽  
Mitul D Patel ◽  
...  

This inventory evaluates toxicological effects and hepatoprotective potential of Clerodendron glandulosum.Coleb (CG) aqueous extract. Acute and subchronic toxicity tests were performed using Swiss albino mice as per the guideline of Organisation for Economic Cooperation and Development (OECD). Also, hepatoprotective potential of CG extract was examined in experimental model of carbon tetrachloride (CCl 4)-induced hepatotoxicity. Acute and subchronic toxicity tests revealed that CG extract is non-toxic and its median lethal dose (LD50) value is >5000 mg/kg bodyweight. Also, rats pretreated with CG extract followed by administration of CCl4 recorded significant decrement in plasma marker enzymes of hepatic damage, total bilirubin content and hepatic lipid peroxidation. While, hepatic reduced glutathione, ascorbic acid content, activity levels of superoxide and catalase and plasma total protein content were significantly increased. Microscopic examination of liver showed that pretreatment with CG extract prevented CCl4-induced hepatic damage in CG + CCl 4 group. CG extract has hepatoprotective potential by modulating activity levels of enzymes and metabolites governing liver function and by helping in maintaining cellular integrity of hepatocytes that is comparable with that of standard drug silymarin. CG extract exhibits potent hepatoprotective activity against CCl4-induced hepatic damage but does not exhibit any toxic manifestations.


2020 ◽  
Vol 8 (A) ◽  
pp. 76-83 ◽  
Author(s):  
Rudy Agung Nugroho ◽  
Retno Aryani ◽  
Hetty Manurung ◽  
Rudianto Rudianto ◽  
Widha Prahastika ◽  
...  

BACKGROUND: Ficus deltoidea Jack. leaves have a great potential as traditional medicine, but the safety level of its use is still unknown. AIM: This study aimed to determine the phytochemical contents of the ethanol extract of F. deltoidea leaves and evaluate the level of safety and toxicity through acute and subchronic toxicity tests in mice (Mus musculus). METHODS: The ethanol extract of F. deltoidea leaves was determined for phytochemical contents such as alkaloids, phenolics, flavonoids, coumarin, steroids, saponins, carotenoids, and tannins. In the acute toxicity test, 10 male mice were divided into a control group and the extract treatment group with 2000 mg/kg body weight (BW) dose for 14 days to identify signs of toxicity and mortality. Meanwhile, in the subchronic toxicity test, 25 male mice were divided into control and four treatment groups with various doses (125, 250, 500, and 1000 mg/kg BW), respectively, for 28 days. The toxicological effect was evaluated by observing behavior, signs of toxicity, and changes in BW. At the end of the treatment, hematological and biochemical evaluations were also measured. RESULTS: The results showed that the ethanol extract of F. deltoidea Jack leaves qualitatively contains alkaloids, phenolic, flavonoids, coumarin, and steroids, whereas quantitatively total phenolics, flavonoids, and IC50 were 107.6583211 μg GA/mg, 175.9103641 μg CE/mg, and 103.7484 μg/mL. Moreover, 2000 mg/kg BW dose resulted in no symptoms of toxicity and mortality, indicating that the 50% lethal dose (LD50) was above 2000 mg/kg BW. Meanwhile, there were no behavioral changes, significant differences in weight changes, hematological parameters, and serum biochemistry of mice in subchronic toxicity tests. CONCLUSION: The present study shows that acute and subchronic oral administration of the ethanol extract of F. deltoidea leaves for male mice does not induce clinical symptoms of toxicity or mortality. The LD50 of the ethanol extract of F. deltoidea leaves for mice >2000 mg/kg is considered as practically non-toxic.


2010 ◽  
Vol 2010 ◽  
pp. 1-9 ◽  
Author(s):  
Saveria Pastore ◽  
Liudmila Korkina

The skin is permanently exposed to physical, chemical, and biological aggression by the environment. In addition, acute and chronic inflammatory events taking place in the skin are accompanied by abnormal release of pro-oxidative mediators. In this paper, we will briefly overview the homeostatic systems active in the skin to maintain the redox balance and also to counteract abnormal oxidative stress. We will concentrate on the evidence that a local and/or systemic redox dysregulation accompanies the chronic inflammatory disorder events associated to psoriasis, contact dermatitis, and atopic dermatitis. We will also discuss the fact that several well-established treatments for the therapy of chronic inflammatory skin disorders are based on the application of strong physical or chemical oxidants onto the skin, indicating that, in selected conditions, a further increase of the oxidative imbalance may lead to a beneficial outcome.


1993 ◽  
Vol 264 (1) ◽  
pp. F149-F157 ◽  
Author(s):  
J. Gailit ◽  
D. Colflesh ◽  
I. Rabiner ◽  
J. Simone ◽  
M. S. Goligorsky

Tubular obstruction by detached renal tubular epithelial cells is a major cause of oliguria in acute renal failure. Viable renal tubular cells can be recovered from urine of patients with acute tubular necrosis, suggesting a possible defect in cell adhesion to the basement membrane. To study this process of epithelial cell desquamation in vitro, we investigated the effect of nonlethal oxidative stress on the integrin adhesion receptors of the primate kidney epithelial cell line BS-C-1. Morphological and functional studies of cell adhesion properties included the following: interference reflection microscopy, intravital confocal microscopy and immunocytochemistry, flow cytometric analysis of integrin receptor abundance, and cell-matrix attachment assay. High levels of the integrin subunits alpha 3, alpha v, and beta 1 were detected on the cell surface by fluorescence-activated cell sorting (FACS) analysis, as well as lower levels of alpha 1, alpha 2, alpha 4, alpha 5, alpha 6, and beta 3. Exposure of BS-C-1 cells to nonlethal oxidative stress resulted in the disruption of focal contacts, disappearance of talin from the basal cell surface, and in the redistribution of integrin alpha 3-subunits from predominantly basal location to the apical cell surface. As measured in a quantitative cell attachment assay, oxidative stress decreased BS-C-1 cell adhesion to type IV collagen, laminin, fibronectin, and vitronectin. Defective adhesion was not associated with a loss of alpha 3-, alpha 4-, or alpha v-integrin subunits from the cell surface.(ABSTRACT TRUNCATED AT 250 WORDS)


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