A Translational Metabonomic Assessment of Aristolochic Acid- Induced Nephropathies

Aristolochic acid nephropathy (AAN) is a global term including any form of toxic interstitial nephropathy that is caused either by the ingestion of plants containing aristolochic acids (AA) as part of traditional phytotherapies or by the environmental contaminants in food. Originally, AAN was reported in Belgium in individuals having ingested slimming pills containing powdered root extracts of a Chinese herb, Aristolochia fangchi. However, it is estimated that exposure to AA affects thousands of people all over the world, particularly in the Balkans, Taiwan and China. Despite warnings from the Regulatory Agencies regarding the safety of products containing AA, many AAN cases remain frequently described worldwide. This chapter aims at giving a global picture of AAN through the descriptions of clinical cases and animal models, which were developed to better understand the mode of action of AA when inducing acute/chronic kidney diseases. Major advances in the translational research on biomarkers of AAN are reviewed, with an intended emphasis on the “omics” assessment of this nephrotoxicity

An integrated view of aristolochic acid nephropathy: Update of the literature

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. Moreover, AAN incidence is probably highly underestimated given the presence of AA in traditional herbal remedies worldwide and the weak awareness of the disease. During these two past decades, animal models for AAN have been developed to investigate underlying molecular and cellular mechanisms involved in AAN pathogenesis. Indeed, a more-in-depth understanding of these processes is essential to develop therapeutic strategies aimed to reduce the global and underestimated burden of this disease. In this regard, our purpose was to build a broad overview of what is currently known about AAN. To achieve this goal, we aimed to summarize the latest data available about underlying pathophysiological mechanisms leading to AAN development with a particular emphasis on the imbalance between vasoactive factors as well as a focus on the vascular events often not considered in AAN.SCOPUS: re.jinfo:eu-repo/semantics/publishe

Protective effect of nitric oxide in aristolochic acid-induced toxic acute kidney injury:an old friend with new assets

New Findings: What is the central question of this study? Despite the fact that the pathogenesis of aristolochic acid (AA) nephropathy is still unclear, we sought to determine whether nitric oxide is involved in the underlying mechanism of AA-induced acute kidney injury (AKI). What is the main finding and its importance? Using a model of progressive tubulointerstitial nephritis, in which AA nephropathy exhibits two interconnected phases, an acute phase and a chronic phase of injury, we demonstrated that maintenance of nitric oxide bioavailability is essential to improve the outcome of AA-induced AKI. Aristolochic acid (AA) nephropathy (AAN), a progressive tubulointerstitial injury of toxic origin, is characterized by early and transient acute tubular necrosis. This process has been demonstrated to be associated with reduced nitric oxide (NO) production, which can disrupt the regulation of renal function. In this study, we tested the hypothesis that l-arginine (l-Arg) supplementation could restore renal function and reduce renal injury after AA intoxication. C57BL/6 J male mice were randomly subjected to daily i.p. injection of either sterile saline solution or AA (2.5 mg kg−1) for 4 days. To determine whether AA-induced renal injuries were linked to reduced NO production, l-Arg, a substrate for NO synthase, was supplemented (5%) in drinking water. Mice intoxicated with AA exhibited features of rapid-onset acute kidney injury, including polyuria, significantly increased plasma creatinine concentrations, proteinuria and fractional excretion of sodium (P < 0.05), along with severe proximal tubular cell injury and increased NADPH oxidase 2 (Nox2)-derived oxidative stress (P < 0.05). This was associated with a significant reduction in NO bioavailability. l-Arg supplementation in AA-treated mice significantly increased NO bioavailability, which in turn improved renal function (creatininaemia, polyuria, proteinuria, fractional excreted sodium and N-acetyl-β-d-glucosaminidase enzymuria) and renal structure (tubular necrosis and tubular cell apoptosis). These changes were associated with significant reductions in Nox2 expression and in production of reactive oxygen species and with an increase in antioxidant concentrations. Our results demonstrate that preservation of NO bioavailability leads to renal protection in AA-induced acute kidney injury by reducing oxidative stress and maintaining renal function.SCOPUS: ar.jFLWINinfo:eu-repo/semantics/publishe

Effet in vitro des acides aristolochiques sur la cellule endothéliale

info:eu-repo/semantics/nonPublishe