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Aristolochic acid (AA), a natural nephrotoxin and carcinogen, can induce a progressive tubulointerstitial nephropathy. However, the mechanism by which AA causes renal injury remains largely unknown. Here we reported that the mitochondrial permeability transition (MPT) plays an important role in the renal injury induced by aristolochic acid I (AAI). We found(More)
UNLABELLED Oxygen dynamics in the liver is a central signaling mediator controlling hepatic homeostasis, and dysregulation of cellular oxygen is associated with liver injury. Moreover, the transcription factor relaying changes in cellular oxygen levels, hypoxia-inducible factor (HIF), is critical in liver metabolism, and sustained increase in HIF signaling(More)
Emodin, an anthraquinone derived from a plant and fungi, has been reported to possess potential genotoxicity, but the mechanism is not entirely clear. Here, we report that emodin causes DNA double-strand breaks (DSBs) through stabilization of topoisomerase (Topo) II-DNA cleavage complexes and inhibition of ATP hydrolysis. In our study, emodin did not induce(More)
AbstractAim:The role of CYP1A in the protection of aristolochic acid (AA)I-induced nephrotoxicity has been suggested. In the present study we investigated the effects of β-naphthoflavone (BNF), a non-carcinogen CYP1A inducer, on AAI-induced kidney injury.Methods:Mice were pretreated with 80 mg/kg BNF by daily intraperitoneal injection (ip) for 3 days(More)
Ingestion of aristolochic acid (AA), especially its major constituent aristolochic acid I (AAI), results in severe kidney injury known as aristolochic acid nephropathy (AAN). Although hepatic cytochrome P450s metabolize AAI to reduce its kidney toxicity in mice, the mechanism by which AAI is uptaken by renal cells to induce renal toxicity is largely(More)
Aristolochic acid I (AAI) is the major toxic component of aristolochic acid that causes aristolochic acid nephropathy and Balkan endemic nephropathy. Nitroreduction is an essential metabolic process for AAI rapid clearance in different species including humans. However, which enzyme participates in AAI nitroreduction in vivo and whether this metabolic(More)
BACKGROUND & AIMS Hypoxic inflammation (decreased oxygen tension at sites of inflammation) is a feature of inflammatory bowel disease (IBD). The hypoxia response is mediated by the transcription factors hypoxia-inducible factor (HIF) 1α and endothelial PAS domain protein 1 (EPAS1 or HIF2α), which are induced in intestinal tissues of patients with IBD. HIF1α(More)
Changes in cellular oxygen tension play important roles in physiological processes including development and pathological processes such as tumor promotion. The cellular adaptations to sustained hypoxia are mediated by hypoxia-inducible factors (HIFs) to regulate downstream target gene expression. With hypoxia, the stabilized HIF-α and aryl hydrocarbon(More)
Baicalin (BA) exhibits anti-inflammatory effect in vivo and in vitro and is used to treat inflammatory diseases. Here, we report that BA inhibits the activation of macrophage and protects mice from macrophage-mediated endotoxin shock. The experiments in vitro showed BA suppressed the increased generation of nitric oxide (NO) and expression of inducible(More)
The mTOR complex 1 (mTORC1) and endoplasmic reticulum (ER) stress pathways are critical regulators of intestinal inflammation and colon cancer growth. Sestrins are stress-inducible proteins, which suppress both mTORC1 and ER stress; however, the role of Sestrins in colon physiology and tumorigenesis has been elusive due to the lack of studies in human(More)