Nephrotoxicity study of Aristolochia fangchi in rats by metabonomics

Liang, Qi; Ni, Cheng; Xie, Ming; Zhang, Qi; Zhang, Yanxia; Yan, Xianzhong; Yang, Mei; Peng, Shuangqing; Zhang, Yuzhong

doi:10.3736/jcim20090808

Cited by 8 publications

(4 citation statements)

References 9 publications

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“…Ginkgo biloba leaves exert multidirectional lipid-lowering effects on the rat metabonome, including limitation of the absorption of cholesterol, inactivation of HMGCoA, and favorable regulation of profiles of essential polyunsaturated fatty acid [59]. Recently, changes of metabolites in rat urine after treatment with Aristolochia fangchi decoction were studied by the metabolomic method [60]. High-dose Aristolochia fangchi can induce nephrotoxicity, and its seriousness corresponds to the duration of ad- ministration.…”

Section: Metabolomic Analysis Of Chmmentioning

confidence: 99%

Metabolomics: Towards Understanding Traditional Chinese Medicine

et al. 2010

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Section: Metabolomic Analysis Of Chmmentioning

confidence: 99%

Metabolomics: Towards Understanding Traditional Chinese Medicine

et al. 2010

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“…We noted significant increases in hippurate levels in both daytime and night‐time samples. One of the several known uremic toxins often measured, elevated hippurate levels indicate tubulointerstitial injury and structural damage of glomeruli and tubular endothelial cells in the kidney (Liang et al, ; Rhee et al, ). Upsets in hippurate levels disrupt the formation of acetyl coenzyme‐A (acetyl‐CoA), which subsequently affects adenosine triphosphate (ATP) generation and energy production (tricarboxylic acid [TCA] cycle) (Lees, Swann, Wilson, Nicholson, & Holmes, ).…”

Section: Discussionmentioning

confidence: 99%

Nuclear magnetic resonance‐ and mass spectrometry‐based metabolomics to study maleic acid toxicity from repeated dose exposure in rats

Chen

et al. 2017

J of Applied Toxicology

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Maleic acid (MA), a chemical intermediate used in many consumer and industrial products, was intentionally adulterated in a variety of starch-based foods and instigated food safety incidents in Asia. We aim to elucidate possible mechanisms of MA toxicity after repeated exposure by (1) determining the changes of metabolic profile using H nuclear magnetic resonance spectroscopy and multivariate analysis, and (2) investigating the occurrence of oxidative stress using liquid chromatography tandem mass spectrometry by using Sprague-Dawley rat urine samples. Adult male rats were subjected to a 28 day subchronic study (0, 6, 20 and 60 mg kg ) via oral gavage. Urine was collected twice a day on days 0, 7, 14, 21 and 28; organs underwent histopathological examination. Changes in body weight and relative kidney weights in medium- and high-dose groups were significantly different compared to controls. Morphological alterations were evident in the kidneys and liver. Metabolomic results demonstrated that MA exposure increases the urinary concentrations of 8-hydroxy-2'-deoxyguanosine, 8-nitroguanine and 8-iso-prostaglandin F ; levels of acetoacetate, hippurate, alanine and acetate demonstrated time- and dose-dependent variations in the treatment groups. Findings suggest that MA consumption escalates oxidative damage, membrane lipid destruction and disrupt energy metabolism. These aforementioned changes in biomarkers and endogenous metabolites elucidate and assist in characterizing the possible mechanisms by which MA induces nephro- and hepatotoxicity.

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“…In the M0.5 and BF0.5 groups, only glucose concentration was elevated in urine which may suggest a minor degree of proximal tubular lesion as we detected in the histopathological examination. In other metabolomic studies of AA nephrotoxicity, increase in glucose and lactate concentration in urine accompanying renal proximal tubular lesions has been detected in rats [25, 26]. Another study indicated that the AA acute kidney injury caused diffuse degeneration of the proximal tubular epithelium [39].…”

Section: Resultsmentioning

confidence: 99%

“…Liang et al used 1 H NMR to study renal toxicity of Aristolochia fangchi in rats, and the AA equivalent dose they used was 3.7 mg/kg/day for 4 weeks. Renal toxicity was detected at 2 weeks in their study [26]. Chen et al used LC-MS to investigate AA and Aristolochia manshuriensis nephrotoxicity in rats, and the equivalent AA dose of A. manshuriensis they used was 96 mg/kg/day for 4 consecutive days.…”

Section: Introductionmentioning

confidence: 99%

Metabolomic Analysis of Complex Chinese Remedies: Examples of Induced Nephrotoxicity in the Mouse from a Series of Remedies Containing Aristolochic Acid

Tsai

Kang

Lee

et al. 2013

Evidence-Based Complementary and Alternative Medicine

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Aristolochic acid nephropathy is caused by aristolochic acid (AA) and AA-containing herbs. In traditional Chinese medicine, a principle called “Jun-Chen-Zou-Shi” may be utilized to construct a remedial herbal formula that attempts to mitigate the toxicity of the main ingredient. This study used Bu-Fei-A-Jiao-Tang (BFAJT) to test if the compound remedy based on a principle of “Jun-Chen-Zou-Shi” can decrease the toxicity of AA-containing herbs. We compared the three toxicities of AA standard, Madouling (an Aristolochia herb), and a herbal formula BFAJT. AA standard was given for BALB/c mice at a dose of 5 mg/kg bw/day or 7.5 mg/kg bw/day for 10 days. Madouling and BFAJT were given at an equivalence of AA 0.5 mg/kg bw/day for 21 days. Nephrotoxicity was evaluated by metabolomics and histopathology. The urinary metabolomics profiles were characterized by 1H NMR spectroscopy. The spectral data was analyzed with partial least squares discriminant analysis, and the significant differential metabolites between groups were identified. The result showed different degrees of acute renal tubular injuries, and metabolomics analysis found that the kidney injuries were focused in proximal renal tubules. Both metabolomics and pathological studies revealed that AA standard, Madouling, and BFAJT were all nephrotoxicants. The compositions of the compound remedy did not diminish the nephrotoxicity caused by AA.

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Nephrotoxicity study of Aristolochia fangchi in rats by metabonomics

Abstract: High-dose Aristolochia fangchi can induce renal lesion and its seriousness is correspondent to the lasting of administration. Aristolochia fangchi may also have toxicity on liver.

Cited by 8 publications

References 9 publications

Metabolomics: Towards Understanding Traditional Chinese Medicine

Metabolomics: Towards Understanding Traditional Chinese Medicine

Nuclear magnetic resonance‐ and mass spectrometry‐based metabolomics to study maleic acid toxicity from repeated dose exposure in rats

Metabolomic Analysis of Complex Chinese Remedies: Examples of Induced Nephrotoxicity in the Mouse from a Series of Remedies Containing Aristolochic Acid

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