scholarly journals Nephroprotective Role of Resveratrol and Ursolic Acid in Aristolochic Acid Intoxicated Zebrafish

Toxins ◽  
2015 ◽  
Vol 7 (1) ◽  
pp. 97-109 ◽  
Author(s):  
Yu-Ju Ding ◽  
Chiao-Yin Sun ◽  
Chi-Chung Wen ◽  
Yau-Hung Chen
2009 ◽  
Vol 9 ◽  
pp. 1360-1373 ◽  
Author(s):  
Ljubinka Jankovic Velickovic ◽  
Takanori Hattori ◽  
Vladisav Stefanovic

The role of aristolochic acid in the etiology of Balkan endemic nephropathy (BEN) and associated upper urothelial carcinoma (UUC) was recently confirmed. The aim of this study was to determine the marker(s) specific for BEN-associated UUC. A total of 82 patients with UUC (38 from the BEN region and 44 control tumors) were included in the study. The Ki-67 index in BEN tumors correlated with the grade and multifocality (p< 0.05), but in regression analysis, only the grade of BEN tumor. The p53 index was significantly higher in BEN than in control tumors (p< 0.05), as well as the alteration of p53 (p< 0.05). BEN low-stage tumors, tumors without limphovascular invasion (LVI), and tumors of the renal pelvis had a higher p53 index than the control tumors (p< 0.05, 0.01, 0.05, respectively). The Ki-67 index was higher in control tumors with high-stage and solid growth than in BEN UUC (p < 0.050, 0.005). The Ki-67 correlated with the grade, growth, stage, LVI, and multifocality of UUC on the best way, but not with the group. In regression analysis, only multifocality of UUC had predictive influence on Ki-67 activity (p< 0.001). P53 correlated with the grade, growth, and group (p< 0.05). This investigation identifies the p53 pathway as the specific cell cycle marker involved in BEN-associated UUC.


2020 ◽  
Vol 31 (12) ◽  
pp. 2773-2792
Author(s):  
Markus Sellmayr ◽  
Moritz Roman Hernandez Petzsche ◽  
Qiuyue Ma ◽  
Nils Krüger ◽  
Helen Liapis ◽  
...  

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.


2016 ◽  
Vol 14 (4) ◽  
pp. 3243-3250 ◽  
Author(s):  
Ting Xiang ◽  
Zhangbin Yang ◽  
Baoguo Sun ◽  
Haoxuan Luo ◽  
Shijun Zhang ◽  
...  

2011 ◽  
Vol 8 (6) ◽  
pp. 2183-2192 ◽  
Author(s):  
Xiang Xue ◽  
Li-Kun Gong ◽  
Kazuya Maeda ◽  
Yang Luan ◽  
Xin-Ming Qi ◽  
...  

1997 ◽  
Vol 78 (2) ◽  
pp. 734-745 ◽  
Author(s):  
John I. Glendinning ◽  
Thomas T. Hills

Glendinning, John I. and Thomas T. Hills. Electrophysiological evidence for two transduction pathways within a bitter-sensitive taste receptor. J. Neurophysiol. 78: 734–745, 1997. Among the sapid stimuli, those that elicit bitter taste are the most abundant and structurally diverse. To accommodate this diversity, animals are thought to use multiple bitter transduction pathways. We examined the role of individual taste receptor cells (TRCs) in this transduction process by focusing on one of the taste organs, or chemosensilla, of a caterpillar ( Manduca sexta). This chemosensillum (the lateral styloconicum) contains four functionally distinct TRCs: the salt, sugar, inositol, and deterrent TRCs, which are known to respond strongly to, in respective order, salts, sugars, inositol, and compounds humans describe as bitter. Using an extracellular recording technique, we tested three hypotheses for how a structurally diverse array of bitter compounds (salicin, caffeine, and aristolochic acid) could excite the same chemosensillum: several TRCs within the lateral styloconica respond to the bitter compounds; only the deterrent TRC responds to the bitter compounds, through a single transduction pathway; and only the deterrent TRC responds to the bitter compounds, but through multiple transduction pathways. To discriminate among these hypotheses, we tested five predictions. The first addressed how many TRCs within the lateral styloconica responded to the bitter compounds. Subsequent predictions were based on the results of the test of the first prediction and assumed that only the deterrent TRC responded to these compounds. These latter predictions addressed whether the bitter compounds acted through one or multiple transduction pathways. We obtained evidence consistent with the third hypothesis: only the deterrent TRC responded to the bitter compounds; the temporal patterns of firing and concentration-response curves elicited by caffeine and salicin were similar to each other, but different from those elicited by aristolochic acid; the patterns of sensory adaptation and disadaptation elicited by caffeine and salicin were similar to each another, but different from those elicited by aristolochic acid; reciprocal cross-adaptation occurred between caffeine and salicin, but not between aristolochic acid and caffeine or aristolochic acid and salicin; and the responsiveness of individual deterrent TRCs to caffeine and salicin correlated significantly, whereas that to aristolochic acid and caffeine or aristolochic acid and salicin did not. Taken together, these results indicate that the deterrent TRC contains at least two excitatory transduction pathways: one responds to caffeine and salicin and the other to aristolochic acid. To our knowledge, this is the first direct support for the existence of two bitter transduction pathways within a single TRC.


2019 ◽  
Vol 115 ◽  
pp. 108917 ◽  
Author(s):  
Xiu Yang ◽  
Daniel Thorngren ◽  
Qi Chen ◽  
Ming Wang ◽  
Xiangcheng Xie

2020 ◽  
Vol 2020 ◽  
pp. 1-8
Author(s):  
Ping-Hsun Lu ◽  
Hsun-Yao Lee ◽  
Yan-Liang Liou ◽  
Sheng-Fen Tung ◽  
Ko-Li Kuo ◽  
...  

Zhibai Dihuang Wan (ZDW) is an eight-herbal formula of traditional Chinese medicine. Clinically, it regulated immune activity and was used to treat diabetes and renal disease. In this study, we aimed to explore the nephroprotective effect of ZDW in an aristolochic acid- (AA-) intoxicated zebrafish model. We used a green fluorescent kidney transgenic zebrafish to evaluate the nephroprotective effects of ZDW by recording subtle changes in the kidney. Our results demonstrated that ZDW treatment can attenuate AA-induced kidney malformations (60% for AA-treated, 47% for pretreatment with ZDW, and 17% for cotreatment ZDW with AA, n = 50 ). Furthermore, we found that the expression levels of tnfα and mpo were decreased either in pretreatment or cotreatment groups. In conclusion, our findings revealed that AA-induced nephrotoxicities can be attenuated by ZDW. Therefore, we believe that zebrafish represent an efficient model for screening AA-protective Chinese medicine.


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