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Aristolochic acid nephropathy

Josip Samardzic, Sefik Hasukic
Objectives: Endemic nephropathy (EN) is a chronic tubulointerstitial renal disease associated with increased incidence of upper urinary tract urothelial cancer (UTUC) occurring predominantly in geographically limited areas in villages along big Danube river. Based on results obtained by the research it is confirmed that aristolochic acid is causative agent of endemic nephropathy (EN). Aim: The aim of this study was to determine characteristics of UTUC in two endemic areas and analyze trends in 5-year period...
December 2017: Medical Archives
Sandybell Anorga, Jessica M Overstreet, Lucas L Falke, Jiaqi Tang, Roel G Goldschmeding, Paul J Higgins, Rohan Samarakoon
Although yes-associated protein (YAP) and transcriptional coactivator with PDZ-binding motif (TAZ), nuclear transducers of the Hippo pathway, are mostly silent in adult organs, aberrant activation of YAP/TAZ promotes tumorigenesis and abnormal tissue repair. The extent of involvement of TAZ in chronic kidney disease (CKD) is unknown. In our study, increased TAZ nuclear accumulation and expression in the tubulointerstitium was readily evident in 3 models of renal injury including obstructive, aristolochic acid (AA), and diabetic nephropathy, correlating with fibrosis progression...
January 3, 2018: FASEB Journal: Official Publication of the Federation of American Societies for Experimental Biology
Alexandra T Gruia, Camelia Oprean, Alexandra Ivan, Ada Cean, Mirabela Cristea, Lavinia Draghia, Roxana Damiescu, Nikola M Pavlovic, Virgil Paunescu, Calin A Tatu
Aristolochic acids (AAs) are carcinogenic and nephrotoxic plant alkaloids present in Aristolochia species, used in traditional medicine. Recent biomolecular and environmental studies have incriminated these toxins as an etiological agent in Balkan endemic nephropathy (BEN), a severe kidney disease occurring in the Balkan Peninsula. The questions on how the susceptible populations are exposed to these toxins have not yet been clearly answered. Exposure to AAs through the food chain, and environmental pollution (soil/dust), could provide an explanation for the presence of BEN in the countries where no folkloric use of the plant has been documented (Bulgaria, Croatia)...
December 29, 2017: Environmental Geochemistry and Health
Ji Li, Mincheng Zhang, Yong Mao, Yimao Li, Xiaoxia Zhang, Xuehan Peng, Feng Yu
Aristolochic acid I (AA-I), one of the main active components in Aristolochaia herbs, may induce aristolochic acid nephropathy (AAN). Renal interstitial fibrosis is one of the most typical features of AAN. To investigate the mechanism of Aristolochic acid I (AA-I) -induced renal epithelial-mesenchymal transition (EMT) and determine the role of aquaporin-1 (AQP1) in this process, we established an AA-I-induced EMT model in human proximal tubular epithelial cells (HK-2 cells). Morphological examination, MTT assay, and Western blot analysis were performed...
June 2018: Journal of Cellular Physiology
Tsai-Kun Wu, Ying-Ru Pan, Hsueh-Fang Wang, Chyou-Wei Wei, Yung-Luen Yu
Aristolochic acid (AA) is a component identified in traditional Chinese remedies for the treatment of arthritic pain, coughs and gastrointestinal symptoms. However, previous studies have indicated that AA can induce oxidative stress in renal cells leading to nephropathy. α‑tocopherol exists in numerous types of food, such as nuts, and belongs to the vitamin E isoform family. It possesses antioxidant activities and has been used previously for clinical applications. Therefore, the aim of the present study was to determine whether α‑tocopherol could reduce AA‑induced oxidative stress and renal cell cytotoxicity, determined by cell survival rate, reactive oxygen species detection and apoptotic features...
January 2018: Molecular Medicine Reports
Senaid Trnacevic, Edin Nislic, Emir Trnacevic, Emir Tulumovic
Introduction: Balkan endemic nephropathy (BEN) is a chronic irreversible interstitial sclerosis, for which over the last 25 years, chronic exposure to aristolochic acid from the contaminated cereal seeds has been considered the most likely cause. The aim of our research is to reevaluate trends of disease and to try to obtain new information about practical implementing of in-field screening of BEN, and to find indicators or a reliable biomarker for an early detection of the disease, especially for in field conditions...
September 2017: Materia Socio-medica
Václav Martínek, František Bárta, Petr Hodek, Eva Frei, Heinz H Schmeiser, Volker M Arlt, Marie Stiborová
Abstract: The herbal drug aristolochic acid, a natural mixture of 8-methoxy-6-nitrophenanthro[3,4-d]-1,3-dioxole-5-carboxylic acid (AAI) and 6-nitrophenanthro[3,4-d]-1,3-dioxole-5-carboxylic acid (AAII), is derived from Aristolochia species and is the cause of two nephropathies. Ingestion of aristolochic acid is associated with the development of urothelial tumors linked with aristolochic acid nephropathy and is implicated in the development of Balkan endemic nephropathy-associated urothelial tumors...
2017: Monatshefte Für Chemie
Marie Stiborová, Volker M Arlt, Heinz H Schmeiser
Aristolochic acid (AA) is a plant alkaloid that causes aristolochic acid nephropathy (AAN) and Balkan endemic nephropathy (BEN), unique renal diseases frequently associated with upper urothelial cancer (UUC). This review summarizes the significance of AA-derived DNA adducts in the aetiology of UUC leading to specific A:T to T:A transversion mutations (mutational signature) in AAN/BEN-associated tumours, which are otherwise rare in individuals with UCC not exposed to AA. Therefore, such DNA damage produced by AA-DNA adducts is one rare example of the direct association of exposure and cancer development (UUC) in humans, confirming that the covalent binding of carcinogens to DNA is causally related to tumourigenesis...
October 14, 2017: International Journal of Molecular Sciences
Moko Zeniya, Takayasu Mori, Naofumi Yui, Naohiro Nomura, Shintaro Mandai, Kiyoshi Isobe, Motoko Chiga, Eisei Sohara, Tatemitsu Rai, Shinichi Uchida
Kidney fibrosis and fibrogenesis significantly exacerbate chronic kidney disease (CKD) progression and are essential therapeutic targets. Bortezomib (BZM) is a proteasome inhibitor used for the treatment of multiple myeloma (MM). Several studies have demonstrated that BZM attenuates renal impairment in patients with MM, although this effect is generally considered to be the result of MM remission. Recently, several studies on BZM reported anti-fibrotic effects on liver and skin in experimental animal models...
October 12, 2017: Scientific Reports
Suxian Chen, Yadi Wang, Yizeng Wan
Aristolochic acid is a component of many types of Chinese medicine, which are commonly used to treat almost all human diseases. However, aristolochic acid may cause nephropathy. Urotensin II (UII) and transforming growth factor (TGF)‑β1 are important signaling factors, which are expressed at elevated levels during the development of nephropathy. However, the association between UII and TGF‑β1 expression remains unclear. In the current study, the regulatory association between UII and TGF‑β1 expression was investigated using a rat aristolochic acid nephropathy model and the NRK‑52E cell line...
November 2017: Molecular Medicine Reports
Inès Jadot, Vanessa Colombaro, Blanche Martin, Isabelle Habsch, Olivia Botton, Joëlle Nortier, Anne-Emilie Declèves, Nathalie Caron
Aristolochic Acid (AA) nephropathy (AAN) is a progressive tubulointerstitial nephritis characterized by an early phase of acute kidney injury (AKI) leading to chronic kidney disease (CKD). The reduced nitric oxide (NO) bioavailability reported in AAN might contribute to renal function impairment and progression of the disease. We previously demonstrated that L-arginine (L-Arg) supplementation is protective in AA-induced AKI. Since the severity of AKI may be considered a strong predictor of progression to CKD, the present study aims to assess the potential benefit of L-Arg supplementation during the transition from the acute phase to the chronic phase of AAN...
2017: PloS One
Romain Boissier, Vital Hevia, Harman Max Bruins, Klemens Budde, Arnaldo Figueiredo, Enrique Lledó-García, Jonathon Olsburgh, Heinz Regele, Claire Fraser Taylor, Rhana Hassan Zakri, Cathy Yuhong Yuan, Alberto Breda
CONTEXT: Renal transplantation is the gold standard renal replacement therapy in end-stage renal disease owing to its superior survival and quality of life compared with dialysis. When the potential recipient has a history of cancer, the waiting period before renal transplantation is usually based on the Cincinnati Registry. OBJECTIVE: To systematically review all available evidence on the risk of cancer recurrence in end-stage renal disease patients with a history of urological cancer...
January 2018: European Urology
Johanna Michl, Olusheyi Bello, Geoffrey C Kite, Monique S J Simmonds, Michael Heinrich
Species of Asarum are used in traditional Chinese medicine and, similar to members of the genus Aristolochia, they contain aristolochic acid analogs (AAAs). These compounds are known for their nephrotoxic and carcinogenic effects. So far, the phytochemistry and nephrotoxicity of species of Asarum is not well studied. A high-resolution LC-MS-based metabolomic approach was used to study the phytochemical variation in medicinally used Asarum species. The cytotoxicity of the samples was assessed using human kidney (HK-2) cells...
2017: Frontiers in Pharmacology
Sibylle Schäfer, Stefan Schwaiger, Hermann Stuppner
Antidesma ghaesembilla is an important medicinal and food plant in many Asian countries. Ten substances could be isolated from the dichloromethane and methanol extract: sitostenone (3), daucosterol (4), chavibetol (5), asperphenamate (6), protocatechuic acid (7), vanillic acid-4-O-β-D-glucoside (8), 1-O-β-D-glucopyranosyl-3-O-methyl-phloroglucinol (9), and aristolic acid II-8-O-β-D-glucoside (10), and two new aristolic acid derivatives, 10-amino-5,7-dimethoxy-aristolic acid II (= 6-amino-9,11-dimethoxyphenanthro[3,4-d]-1,3-dioxole-5-carboxylic acid; 1) and 5,7-dimethoxy-aristolochic acid II (= 9,11-dimethoxy-6-nitrophenantro[3,4-d]-1,3-dioxole-5-carboxylic acid; 2)...
August 2017: Planta Medica
Guang-Xing Shui, Dong Sang, Xun Yin, Yun Cai, Wei Sun
Objectives. The effects of the traditional formula Dahuang Fuzi Decoction (DFD) on chronic aristolochic acid nephropathy (AAN) in mice and its underlying mechanisms were studied. Methods. Mice were randomly divided into the following six groups: the control group, the model group (AAN), the saline-treated group (AAN + vehicle), the normal dose DFD-treated group (AAN + NDFD), the high dose DFD-treated group (AAN + HDFD), and the rosiglitazone treated group (AAN + Rosi). After treating for 8 weeks, 24 h urine and blood samples were collected and the mice sacrificed to study the biochemical parameters associated with renal function...
2017: Evidence-based Complementary and Alternative Medicine: ECAM
Xiang-Cheng Xie, Ning Zhao, Qun-Hong Xu, Xiu Yang, Wen-Kai Xia, Qi Chen, Ming Wang, Xiao Fei
Aristolochic acid nephropathy remains a leading cause of chronic kidney disease (CKD), however few treatment strategies exist. Emerging evidence has shown that H2 relaxin (RLX) possesses powerful antifibrosis and anti-apoptotic properties, therefore we aimed to investigate whether H2 relaxin can be employed to reduce AA-induced cell apoptosis. Human proximal tubular epithelial (HK-2) cells exposed to AA-I were treated with or without administration of H2 RLX. Cell viability was examined using the WST-8 assay...
June 2017: Apoptosis: An International Journal on Programmed Cell Death
Joo-Hark Yi, Sang-Woong Han, Wan-Young Kim, Jin Kim, Moon-Hyang Park
Background/Aims: This study was designed to investigate the roles of aristolochic acid I (AA-I) and hypokalemia in acute aristolochic acid nephropathy (AAN). Methods: After an adaptation period (1 week), a total of 40 C57BL/6 mice (male, 8 weeks old) were divided into four groups: I (control group), II (low potassium [K] diet), III (normal K diet with administration of AA-I [10 mg/kg weight]), and IV (low K diet with AA-I). After collecting 24 hours of urine at 2 weeks, the mice were sacrificed, and their blood and kidneys were obtained to perform immunochemical staining and/or Western blot analysis...
February 15, 2017: Korean Journal of Internal Medicine
Inès Jadot, Anne-Emilie Declèves, Joëlle Nortier, Nathalie Caron
The term "aristolochic acid nephropathy" (AAN) is used to include any form of toxic interstitial nephropathy that is caused either by ingestion of plants containing aristolochic acids (AA) as part of traditional phytotherapies (formerly known as "Chinese herbs nephropathy"), or by the environmental contaminants in food (Balkan endemic nephropathy). It is frequently associated with urothelial malignancies. Although products containing AA have been banned in most of countries, AAN cases remain regularly reported all over the world...
January 29, 2017: International Journal of Molecular Sciences
Ying Fan, Wenzhen Xiao, Kyung Lee, Fadi Salem, Jiejun Wen, Li He, Jing Zhang, Yang Fei, Dongsheng Cheng, Hongda Bao, Yumei Liu, Fujun Lin, Gengru Jiang, Zhiyong Guo, Niansong Wang, John Cijiang He
Several animal studies have shown an important role for endoplasmic reticulum (ER) stress in AKI, whereas human studies are lacking. We recently reported that Reticulon-1A (RTN1A) is a key mediator of ER stress and kidney cell injury. Here, we investigated whether modulation of RTN1A expression during AKI contributes to the progression to CKD. In a retrospective study of 51 patients with AKI, increased expression of RTN1A and other ER stress markers were associated with the severity of kidney injury and with progression to CKD...
July 2017: Journal of the American Society of Nephrology: JASN
Rozaini Abdullah, Leolean Nyle Diaz, Sebastiaan Wesseling, Ivonne M C M Rietjens
After the incidences of induction of aristolochic acid nephropathy after consumption of herbal weight loss preparations that accidentally contained aristolochic acids (AAs), several countries defined national restrictions on the presence of AAs in food, including plant food supplements (PFS) and herbal products. This study investigates whether the risks associated with exposure to AAs via PFS and herbal products are at present indeed negligible. Data reported in literature on AA levels in PFS and other herbal products and also obtained from a new series of PFS in the present study were used to calculate the estimated daily intakes (EDIs) and corresponding margins of exposure (MOEs)...
February 2017: Food Additives & Contaminants. Part A, Chemistry, Analysis, Control, Exposure & Risk Assessment
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