scholarly journals Role of Cytochromes P450 1A1/2 in Detoxication and Activation of Carcinogenic Aristolochic Acid I: Studies with the Hepatic NADPH:Cytochrome P450 Reductase Null (HRN) Mouse Model

2011 ◽  
Vol 121 (1) ◽  
pp. 43-56 ◽  
Author(s):  
Kateřina Levová ◽  
Michaela Moserová ◽  
Věra Kotrbová ◽  
Miroslav Šulc ◽  
Colin J. Henderson ◽  
...  
Keyword(s):  
Mouse Model ◽  
Aristolochic Acid ◽  
Cytochromes P450 ◽  
P450 Reductase ◽  
Nadph:Cytochrome P450 Reductase ◽  
Aristolochic Acid I

Role of hepatic cytochromes P450 in bioactivation of the anticancer drug ellipticine: Studies with the hepatic NADPH:Cytochrome P450 reductase null mouse

2008 ◽  
Vol 226 (3) ◽  
pp. 318-327 ◽  
Author(s):  
Marie Stiborová ◽  
Volker M. Arlt ◽  
Colin J. Henderson ◽  
C. Roland Wolf ◽  
Věra Kotrbová ◽  
...  
Keyword(s):  
Anticancer Drug ◽  
Cytochromes P450 ◽  
Null Mouse ◽  
P450 Reductase ◽  
Nadph:Cytochrome P450 Reductase

scholarly journals Only Hyperuricemia with Crystalluria, but not Asymptomatic Hyperuricemia, Drives Progression of Chronic Kidney Disease

2020 ◽  
Vol 31 (12) ◽  
pp. 2773-2792
Author(s):  
Markus Sellmayr ◽  
Moritz Roman Hernandez Petzsche ◽  
Qiuyue Ma ◽  
Nils Krüger ◽  
Helen Liapis ◽  
...  
Keyword(s):  
Mass Spectrometry ◽  
Aristolochic Acid ◽  
Interstitial Fibrosis ◽  
Ckd Progression ◽  
Fticr Mass Spectrometry ◽  
Progressive Decline ◽  
Granulomatous Interstitial Nephritis ◽  
Crystal Nephropathy ◽  
Aristolochic Acid I

BackgroundThe roles of asymptomatic hyperuricemia or uric acid (UA) crystals in CKD progression are unknown. Hypotheses to explain links between UA deposition and progression of CKD include that (1) asymptomatic hyperuricemia does not promote CKD progression unless UA crystallizes in the kidney; (2) UA crystal granulomas may form due to pre-existing CKD; and (3) proinflammatory granuloma-related M1-like macrophages may drive UA crystal-induced CKD progression.MethodsMALDI-FTICR mass spectrometry, immunohistochemistry, 3D confocal microscopy, and flow cytometry were used to characterize a novel mouse model of hyperuricemia and chronic UA crystal nephropathy with granulomatous nephritis. Interventional studies probed the role of crystal-induced inflammation and macrophages in the pathology of progressive CKD.ResultsAsymptomatic hyperuricemia alone did not cause CKD or drive the progression of aristolochic acid I-induced CKD. Only hyperuricemia with UA crystalluria due to urinary acidification caused tubular obstruction, inflammation, and interstitial fibrosis. UA crystal granulomas surrounded by proinflammatory M1-like macrophages developed late in this process of chronic UA crystal nephropathy and contributed to the progression of pre-existing CKD. Suppressing M1-like macrophages with adenosine attenuated granulomatous nephritis and the progressive decline in GFR. In contrast, inhibiting the JAK/STAT inflammatory pathway with tofacitinib was not renoprotective.ConclusionsAsymptomatic hyperuricemia does not affect CKD progression unless UA crystallizes in the kidney. UA crystal granulomas develop late in chronic UA crystal nephropathy and contribute to CKD progression because UA crystals trigger M1-like macrophage-related interstitial inflammation and fibrosis. Targeting proinflammatory macrophages, but not JAK/STAT signaling, can attenuate granulomatous interstitial nephritis.

scholarly journals Traditional Chinese medicine: Pivotal role of the spleen in the metabolism of aristolochic acid I in rats is dependent on oatp2a1

2016 ◽  
Vol 14 (4) ◽  
pp. 3243-3250 ◽  
Author(s):  
Ting Xiang ◽  
Zhangbin Yang ◽  
Baoguo Sun ◽  
Haoxuan Luo ◽  
Shijun Zhang ◽  
...  
Keyword(s):  
Chinese Medicine ◽  
Traditional Chinese Medicine ◽  
Aristolochic Acid ◽  
Pivotal Role ◽  
Aristolochic Acid I

Critical Role of Organic Anion Transporters 1 and 3 in Kidney Accumulation and Toxicity of Aristolochic Acid I

2011 ◽  
Vol 8 (6) ◽  
pp. 2183-2192 ◽  
Author(s):  
Xiang Xue ◽  
Li-Kun Gong ◽  
Kazuya Maeda ◽  
Yang Luan ◽  
Xin-Ming Qi ◽  
...  
Keyword(s):  
Aristolochic Acid ◽  
Organic Anion ◽  
Critical Role ◽  
Organic Anion Transporters ◽  
Anion Transporters ◽  
Aristolochic Acid I

scholarly journals Protective role of relaxin in a mouse model of aristolochic acid nephropathy

2019 ◽  
Vol 115 ◽  
pp. 108917 ◽  
Author(s):  
Xiu Yang ◽  
Daniel Thorngren ◽  
Qi Chen ◽  
Ming Wang ◽  
Xiangcheng Xie
Keyword(s):  
Mouse Model ◽  
Aristolochic Acid ◽  
Protective Role ◽  
Aristolochic Acid Nephropathy
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