The Aryl Hydrocarbon Receptor in Chronic Kidney Disease: Friend or Foe?

Mo, Yenan; Lu, Zhaoyu; Wang, Lixin; Ji, Chunlan; Zou, Chuan; Liu, Xusheng

doi:10.3389/fcell.2020.589752

Cited by 21 publications

(13 citation statements)

References 112 publications

(123 reference statements)

Supporting

Mentioning

Contrasting

Order By: Relevance

“…These findings show that AhR could be activated by aryl-containing metabolites, which can be retarded by lowering the aryl-containing metabolite levels using dietary flavonoids. Flavonoids also seem to be able to attenuate renal fibrosis and down-regulate the mRNA expression of AhR target genes (Miao et al, 2020;Mo et al, 2020).…”

Section: Clinical Approaches For Uremic Toxin Treatmentmentioning

confidence: 99%

Uremic Toxins: An Alarming Danger Concerning the Cardiovascular System

et al. 2021

View full text Add to dashboard Cite

The kidneys and heart share functions with the common goal of maintaining homeostasis. When kidney injury occurs, many compounds, the so-called “uremic retention solutes” or “uremic toxins,” accumulate in the circulation targeting other tissues. The accumulation of uremic toxins such as p-cresyl sulfate, indoxyl sulfate and inorganic phosphate leads to a loss of a substantial number of body functions. Although the concept of uremic toxins is dated to the 1960s, the molecular mechanisms capable of leading to renal and cardiovascular injuries are not yet known. Besides, the greatest toxic effects appear to be induced by compounds that are difficult to remove by dialysis. Considering the close relationship between renal and cardiovascular functions, an understanding of the mechanisms involved in the production, clearance and overall impact of uremic toxins is extremely relevant for the understanding of pathologies of the cardiovascular system. Thus, the present study has as main focus to present an extensive review on the impact of uremic toxins in the cardiovascular system, bringing the state of the art on the subject as well as clinical implications related to patient’s therapy affected by chronic kidney disease, which represents high mortality of patients with cardiac comorbidities.

show abstract

Section: Clinical Approaches For Uremic Toxin Treatmentmentioning

confidence: 99%

Uremic Toxins: An Alarming Danger Concerning the Cardiovascular System

et al. 2021

View full text Add to dashboard Cite

show abstract

“…It has been reported that activated AhR aggravates renal damage and mediates CKD complications, including cardiovascular disease, anaemia, bone disorders, cognitive dysfunction and malnutrition, and that it influences drug metabolism in individuals with CKD [ 55 ]. There are two AhR signalling pathway.…”

Section: Discussionmentioning

confidence: 99%

Bupi Yishen formula attenuates kidney injury in 5/6 nephrectomized rats via the tryptophan-kynurenic acid-aryl hydrocarbon receptor pathway

Jie

Wang

et al. 2021

BMC Complement Med Ther

Self Cite

View full text Add to dashboard Cite

Background Bupi Yishen Formula (BYF), a patent traditional Chinese medicine (TCM) formulation, has been used in the clinical treatment of chronic kidney disease (CKD). However, the mechanism of action of BYF has not been fully elucidated. Method To investigate the variation in the metabolic profile in response to BYF treatment in a rat model of 5/6 nephrectomy (Nx), rats in the treatment groups received low- or high-dose BYF. At the end of the study, serum and kidney samples were collected for biochemical, pathological, and western blotting analysis. Metabolic changes in serum were analyzed by liquid chromatography-tandem mass spectrometry. Results The results showed that BYF treatment could reduce kidney injury, inhibit inflammation and improve renal function in a dose-dependent manner. In total, 405 and 195 metabolites were identified in negative and positive ion modes, respectively. Metabolic pathway enrichment analysis of differential metabolites based on the Kyoto Encyclopedia of Genes and Genomes database identified 35 metabolic pathways, 3 of which were related to tryptophan metabolism. High-dose BYF reduced the level of kynurenic acid (KA) by more than 50%, while increasing melatonin 25-fold and indole-3-acetic acid twofold. Expression levels of aryl hydrocarbon receptor (AhR), Cyp1A1, and CyP1B1 were significantly reduced in the kidney tissue of rats with high-dose BYF, compared to 5/6 Nx rats. Conclusion BYF has a reno-protective effect against 5/6 Nx-induced CKD, which may be mediated via inhibition of the tryptophan-KA-AhR pathway.

show abstract

Section: Prenatal Environmental Chemical Exposure On Renal Programmingmentioning

confidence: 99%

“…Quite a few environmental chemicals are ligands for AHR, such as TCDD, PCDD, PCDF, PCB, BPA, BaP ( 119 ). In addition to exogenous ligands (i.e., environmental chemicals), AHR signaling can be activated by endogenous ligands like tryptophan metabolites ( 119 ). In patients with kidney disease, the most important AHR ligands are uremic toxins, especially those gut microbiota-derived from tryptophan metabolism.…”

Section: Prenatal Environmental Chemical Exposure On Renal Programmingmentioning

confidence: 99%

Adverse Impact of Environmental Chemicals on Developmental Origins of Kidney Disease and Hypertension

Hsu

Tain

2021

Front. Endocrinol.

View full text Add to dashboard Cite

Chronic kidney disease (CKD) and hypertension are becoming a global health challenge, despite developments in pharmacotherapy. Both diseases can begin in early life by so-called “developmental origins of health and disease” (DOHaD). Environmental chemical exposure during pregnancy can affect kidney development, resulting in renal programming. Here, we focus on environmental chemicals that pregnant mothers are likely to be exposed, including dioxins, bisphenol A (BPA), phthalates, per- and polyfluoroalkyl substances (PFAS), polycyclic aromatic hydrocarbons (PAH), heavy metals, and air pollution. We summarize current human evidence and animal models that supports the link between prenatal exposure to environmental chemicals and developmental origins of kidney disease and hypertension, with an emphasis on common mechanisms. These include oxidative stress, renin-angiotensin system, reduced nephron numbers, and aryl hydrocarbon receptor signaling pathway. Urgent action is required to identify toxic chemicals in the environment, avoid harmful chemicals exposure during pregnancy and lactation, and continue to discover other potentially harmful chemicals. Innovation is also needed to identify kidney disease and hypertension in the earliest stage, as well as translating effective reprogramming interventions from animal studies into clinical practice. Toward DOHaD approach, prohibiting toxic chemical exposure and better understanding of underlying mechanisms, we have the potential to reduce global burden of kidney disease and hypertension.

show abstract

The Aryl Hydrocarbon Receptor in Chronic Kidney Disease: Friend or Foe?

Cited by 21 publications

References 112 publications

Uremic Toxins: An Alarming Danger Concerning the Cardiovascular System

Uremic Toxins: An Alarming Danger Concerning the Cardiovascular System

Bupi Yishen formula attenuates kidney injury in 5/6 nephrectomized rats via the tryptophan-kynurenic acid-aryl hydrocarbon receptor pathway

Adverse Impact of Environmental Chemicals on Developmental Origins of Kidney Disease and Hypertension

Contact Info

Product

Resources

About