Berry fruits modulate kidney dysfunction and urine metabolome in Dahl salt-sensitive rats

Gomes, Andréia; Godinho-Pereira, Joana; Oudot, Carole; Sequeira, Catarina O.; Macià, Alba; Carvalho, Fernanda; Motilva, María‐José; Pereira, Sofia A.; Matzapetakis, Manolis; Brenner, Catherine; Santos, Cláudia N.

doi:10.1016/j.freeradbiomed.2020.05.002

Cited by 9 publications

(12 citation statements)

References 49 publications

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“…The protein-bound fraction (RSSP) was obtained by subtracting the total free fraction from the total fraction. This procedure has been validated by others [ 14 ] and is well established in several publications [ 7 , 20 , 37 , 38 ]. The free oxidized fraction (RSSR) was obtained by subtracting the total free reduced to the total free fraction (RSH).…”

Section: Methodsmentioning

confidence: 82%

“…Moreover, oxidized cysteine exists mainly extracellularly and comprises two dynamic pools, the free oxidized and the CysSSP. Both pools might represent a way to supply cysteine into the cell [ 7 , 16 , 38 , 44 ], so we also analyzed the ratio between them. We observed that longer periods of CIH favors increased free oxidized cysteine instead of CysSSP pool ( Figure 6 E).…”

Section: Resultsmentioning

confidence: 99%

“…The way how AhR is activated by cystine administration, if directly by post-translational modifications or by the action of its catabolism products (taurine, H 2 S, CoA) [ 16 , 38 ] requires further clarification. At the kidney level, the best-known AhR activators are uremic toxins [ 90 ], particularly protein-bound uremic toxins [ 91 ], like p-cresol sulfate and indoxyl sulfate [ 92 , 93 ].…”

Section: Discussionmentioning

confidence: 99%

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Aryl Hydrocarbon Receptor and Cysteine Redox Dynamics Underlie (Mal)adaptive Mechanisms to Chronic Intermittent Hypoxia in Kidney Cortex

et al. 2021

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We hypothesized that an interplay between aryl hydrocarbon receptor (AhR) and cysteine-related thiolome at the kidney cortex underlies the mechanisms of (mal)adaptation to chronic intermittent hypoxia (CIH), promoting arterial hypertension (HTN). Using a rat model of CIH-HTN, we investigated the impact of short-term (1 and 7 days), mid-term (14 and 21 days, pre-HTN), and long-term intermittent hypoxia (IH) (up to 60 days, established HTN) on Cyp1a1 protein level (a sensitive hallmark of AhR activation) and cysteine-related thiol pools. We found that acute and chronic IH had opposite effects on Cyp1a1 and the thiolome. While short-term IH decreased Cyp1a1 and increased protein-S-thiolation, long-term IH increased Cyp1a1 and free oxidized cysteine. In addition, an in vitro administration of cystine, but not cysteine, to human endothelial cells increased Cyp1a1 expression, supporting cystine as a putative AhR activator. This study supports Cyp1a1 as a biomarker of obstructive sleep apnea (OSA) severity and oxidized pools of cysteine as risk indicator of OSA-HTN. This work contributes to a better understanding of the mechanisms underlying the phenotype of OSA-HTN, mimicked by this model, which is in line with precision medicine challenges in OSA.

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Section: Methodsmentioning

confidence: 82%

Section: Resultsmentioning

confidence: 99%

Section: Discussionmentioning

confidence: 99%

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Aryl Hydrocarbon Receptor and Cysteine Redox Dynamics Underlie (Mal)adaptive Mechanisms to Chronic Intermittent Hypoxia in Kidney Cortex

et al. 2021

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“…While being cautious on the species differences that may occur, the study of the mechanisms that regulate the amount of cysteine that reaches the kidney and that re-mains in the body requires a systems biology approach that cannot be achieved in cellular models. In fact, we provided evidence that there is a change in cysteine dynamics in kidney of animal models of HTN that is dependent on the hypertensive stimuli used, i.e., chronic intermittent hypoxia [10,11] vs. high salt consumption [72]. We also observed that cysteine, glutathione and cysteinylglycine have independent dynamics between its three different fractions [10,11,72].…”

Section: Introductionmentioning

confidence: 62%

Cysteine as a Multifaceted Player in Kidney, the Cysteine-Related Thiolome and Its Implications for Precision Medicine

et al. 2022

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In this review encouraged by original data, we first provided in vivo evidence that the kidney, comparative to the liver or brain, is an organ particularly rich in cysteine. In the kidney, the total availability of cysteine was higher in cortex tissue than in the medulla and distributed in free reduced, free oxidized and protein-bound fractions (in descending order). Next, we provided a comprehensive integrated review on the evidence that supports the reliance on cysteine of the kidney beyond cysteine antioxidant properties, highlighting the relevance of cysteine and its renal metabolism in the control of cysteine excess in the body as a pivotal source of metabolites to kidney biomass and bioenergetics and a promoter of adaptive responses to stressors. This view might translate into novel perspectives on the mechanisms of kidney function and blood pressure regulation and on clinical implications of the cysteine-related thiolome as a tool in precision medicine.

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“…Once in circulation, polyphenol metabolites are known to be distributed across a wide variety of tissues and have inclusively been shown to cross the blood–brain barrier. Previous studies carried out in rats have also demonstrated considerable amounts of polyphenol metabolites in kidney tissue, after ingestion of a berries-rich diet [ 101 , 102 , 184 ]. Polyphenol metabolites interact with target tissues and cells, where they can exert relevant biological activities.…”

Section: Polyphenols Bioavailability and Their Relevant Metabolitesmentioning

confidence: 99%

Polyphenols and Their Metabolites in Renal Diseases: An Overview

Guerreiro

Ferreira-Pêgo

Carregosa

et al. 2022

Foods

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Kidney diseases constitute a worldwide public health problem, contributing to morbidity and mortality. The present study aimed to provide an overview of the published data regarding the potential beneficial effects of polyphenols on major kidney diseases, namely acute kidney injury, chronic kidney disease, diabetic nephropathy, renal cancer, and drug-induced nephrotoxicity. This study consists of a bibliographical review including in vitro and in vivo studies dealing with the effects of individual compounds. An analysis of the polyphenol metabolome in human urine was also conducted to estimate those compounds that are most likely to be responsible for the kidney protective effects of polyphenols. The biological effects of polyphenols can be highly attributed to the modulation of specific signaling cascades including those involved in oxidative stress responses, anti-inflammation processes, and apoptosis. There is increasing evidence that polyphenols afford great potential in renal disease protection. However, this evidence (especially when in vitro studies are involved) should be considered with caution before its clinical translation, particularly due to the unfavorable pharmacokinetics and extensive metabolization that polyphenols undergo in the human body. Future research should consider polyphenols and their metabolites that indeed reach kidney tissues.

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Berry fruits modulate kidney dysfunction and urine metabolome in Dahl salt-sensitive rats

Cited by 9 publications

References 49 publications

Aryl Hydrocarbon Receptor and Cysteine Redox Dynamics Underlie (Mal)adaptive Mechanisms to Chronic Intermittent Hypoxia in Kidney Cortex

Aryl Hydrocarbon Receptor and Cysteine Redox Dynamics Underlie (Mal)adaptive Mechanisms to Chronic Intermittent Hypoxia in Kidney Cortex

Cysteine as a Multifaceted Player in Kidney, the Cysteine-Related Thiolome and Its Implications for Precision Medicine

Polyphenols and Their Metabolites in Renal Diseases: An Overview

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