Oral exposure to aristolochic acid I induces gastric histological lesions with non-specific renal injury in rat

Pu, Xiongming; Shen, Jiaying; Deng, Zhongping; Zhang, Zean

doi:10.1016/j.etp.2016.03.003

Cited by 12 publications

(7 citation statements)

References 17 publications

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“…We found that SB and OM altered the pH level of stomach fluid in a similar manner ( S2 Fig ). As a vehicle for dissolving AA [ 28 ], SB slightly increased the renal nephrotoxicity mediated by AMK treatment in our work ( Fig 4 ). It was reported previously that serum CRE levels increased in AAN patients after treated with SB [ 21 ].…”

Section: Discussionsupporting

confidence: 59%

Omeprazole Alleviates Aristolochia manshuriensis Kom-Induced Acute Nephrotoxicity

Wang

Zhang

et al. 2016

PLoS ONE

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Aristolochia manshuriensis Kom (AMK) is a member of the Aristolochiaceae family and is a well-known cause of aristolochic acid (AA) nephropathy. In this study, we investigated the potential of omeprazole (OM) to alleviate AMK-induced nephrotoxicity. We found that OM reduced mouse mortality caused by AMK and attenuated AMK-induced acute nephrotoxicity in rats. OM enhanced hepatic Cyp 1a1/2 and renal Cyp 1a1 expression in rats, as well as CYP 1A1 expression in human renal tubular epithelial cells (HKCs). HKCs with ectopic CYP 1A1 expression were more tolerant to AA than the control cells. Therefore, OM may alleviate AMK-mediated acute nephrotoxicity through induction of CYP 1A1. We suggest that the coadministration of OM might be beneficial for reducing of AA-induced nephrotoxicity.

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Section: Discussionsupporting

confidence: 59%

Omeprazole Alleviates Aristolochia manshuriensis Kom-Induced Acute Nephrotoxicity

Wang

Zhang

et al. 2016

PLoS ONE

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“…Renal toxicity of AAs is observed in both mice and rats after repeat dose (Mengs, 1987; Mengs and Stotzem, 1993). Furthermore, aristolochic acid I (AAI)-induced gastrotoxicity characterized by fore-stomach damage presents prior to renal injury (Pu et al, 2016). In addition, AAI could induce apoptotic cell death in the ovaries and testis of mice and cause severe reduction of organ size and weight (Kwak et al, 2014; Kwak and Lee, 2016).…”

Section: Aristolochic Acid-induced Adverse Reactionsmentioning

confidence: 99%

Systematic Overview of Aristolochic Acids: Nephrotoxicity, Carcinogenicity, and Underlying Mechanisms

et al. 2019

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Aristolochic acids (AAs) are a group of toxins commonly present in the plants of genus Aristolochia and Asarum , which are spread all over the world. Since the 1990s, AA-induced nephropathy (AAN) and upper tract urothelial carcinoma (UTUC) have been reported in many countries. The underlying mechanisms of AAN and AA-induced UTUC have been extensively investigated. AA-derived DNA adducts are recognized as specific biomarkers of AA exposure, and a mutational signature predominantly characterized by A→T transversions has been detected in AA-induced UTUC tumor tissues. In addition, various enzymes and organic anion transporters are involved in AA-induced adverse reactions. The progressive lesions and mutational events initiated by AAs are irreversible, and no effective therapeutic regimen for AAN and AA-induced UTUC has been established until now. Because of several warnings on the toxic effects of AAs by the US Food and Drug Administration and the regulatory authorities of some other countries, the sale and use of AA-containing products have been banned or restricted in most countries. However, AA-related adverse events still occur, especially in the Asian and Balkan regions. Therefore, the use of AA-containing herbal remedies and the consumption of food contaminated by AAs still carry high risk. More strict precautions should be taken to protect the public from AA exposure.

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“…In the liver, the AA mixture is metabolized under anaerobic conditions to the corresponding aristolactam I and II, whereas under aerobic conditions, the only metabolite obtained is the O‐demethylated derivative aristolochic acid Ia (AA Ia), which is a biotransformation product from aristolochic acid I (AA I). AA I is considered to be responsible for the nephrotoxic and carcinogenic effects of AA . The most important human, mouse and rat enzyme that activates AA I in the hepatic and renal cytosolic subcellular fraction is NAD(P)H:quinone oxidoreductase (NQO1), but hepatic microsomal cytochrome P450 (CYP) 1A1/2 and renal microsomal NADPH:CYP reductase (POR) have also been shown to reduce AA I.…”

Section: Commentarymentioning

confidence: 99%

“…AA I is considered to be responsible for the nephrotoxic and carcinogenic effects of AA. 22 The most important human, mouse and rat enzyme that activates AA I in the hepatic and renal cytosolic subcellular fraction is NAD(P)H:quinone oxidoreductase (NQO1), but hepatic microsomal cytochrome P450 (CYP) 1A1/2 and renal microsomal NADPH:CYP reductase (POR) have also been shown to reduce AA I. Moreover, genetic polymorphisms, drugs, smoking habits and environmental chemicals have been identified as important factors that influence the expression levels and activities of these enzymes and might thus explain the interindividual differences in susceptibility to AA toxicity.…”

Section: Doubts Regarding Aa-induced Liver Cancermentioning

confidence: 99%

Recognition of the toxicity of aristolochic acid

Zhang

Xin²,

Sun

et al. 2018

J Clin Pharm Ther

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Summary What is Known and Objective Aristolochic acid (AA) is an abundant compound in Aristolochia plants and various natural herbs. In the 1990s, a slimming formula used in Belgium that contains Aristolochia fangchi was reported to cause kidney damage and bladder cancer, and aristolochic acid nephropathy (AAN) is now well recognized worldwide. In October 2017, researchers reported an AA signature that is closely associated with hepatocellular carcinoma (HCC) worldwide. Comment There are differing opinions on the toxicity of AA, and different countries have taken different measures to address the issue. There is a lack of clarity on the causal role of AA in hepatocarcinogenesis and on the potential underlying mechanisms for the reported nephrotoxicity and carcinogenicity. The toxicity of AA differs depending on gender and age, and other risk factors that could explain the variability in the toxicity of AA remain to be identified. What is New and Conclusion Whether preparations containing AA, such as many Chinese medicines, should be used remains controversial, and this issue warrants further investigation before definite conclusions can be drawn.

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Oral exposure to aristolochic acid I induces gastric histological lesions with non-specific renal injury in rat

Cited by 12 publications

References 17 publications

Omeprazole Alleviates Aristolochia manshuriensis Kom-Induced Acute Nephrotoxicity

Omeprazole Alleviates Aristolochia manshuriensis Kom-Induced Acute Nephrotoxicity

Systematic Overview of Aristolochic Acids: Nephrotoxicity, Carcinogenicity, and Underlying Mechanisms

Recognition of the toxicity of aristolochic acid

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