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2.
Toxins (Basel) ; 14(1)2022 01 12.
Artigo em Inglês | MEDLINE | ID: mdl-35051031

RESUMO

The syndrome of uremic toxicity comprises a complex toxic milieu in-vivo, as numerous uremic substances accumulate and harm the organ systems. Among these substances, toxic and non-toxic players differently interfere with human cells. However, results from animal experiments are not always compatible with the expected reactions in human patients and studies on one organ system are limited in capturing the complexity of the uremic situation. In this narrative review, we present aspects relevant for cellular toxicity research based on our previous establishment of a human spermatozoa-based cell model, as follows: (i) applicability to compare the effects of more than 100 uremic substances, (ii) detection of the protective effects of uremic substances by the cellular responses towards the uremic milieu, (iii) inclusion of the drug milieu for cellular function, and (iv) transferability for clinical application, e.g., hemodialysis. Our technique allows the estimation of cell viability, vitality, and physiological state, not only restricted to acute or chronic kidney toxicity but also for other conditions, such as intoxications of unknown substances. The cellular models can clarify molecular mechanisms of action of toxins related to human physiology and therapy. Identification of uremic toxins retained during acute and chronic kidney injury enables further research on the removal or degradation of such products.


Assuntos
Modelos Biológicos , Espermatozoides/fisiologia , Toxinas Urêmicas/toxicidade , Animais , Linhagem Celular , Humanos , Masculino
3.
Toxins (Basel) ; 13(8)2021 08 17.
Artigo em Inglês | MEDLINE | ID: mdl-34437444

RESUMO

Uremic toxins (UTs) are mainly produced by protein metabolized by the intestinal microbiota and converted in the liver or by mitochondria or other enzymes. The accumulation of UTs can damage the intestinal barrier integrity and cause vascular damage and progressive kidney damage. Together, these factors lead to metabolic imbalances, which in turn increase oxidative stress and inflammation and then produce uremia that affects many organs and causes diseases including renal fibrosis, vascular disease, and renal osteodystrophy. This article is based on the theory of the intestinal-renal axis, from bench to bedside, and it discusses nonextracorporeal therapies for UTs, which are classified into three categories: medication, diet and supplement therapy, and complementary and alternative medicine (CAM) and other therapies. The effects of medications such as AST-120 and meclofenamate are described. Diet and supplement therapies include plant-based diet, very low-protein diet, probiotics, prebiotics, synbiotics, and nutraceuticals. The research status of Chinese herbal medicine is discussed for CAM and other therapies. This review can provide some treatment recommendations for the reduction of UTs in patients with chronic kidney disease.


Assuntos
Nefropatias/tratamento farmacológico , Nefropatias/terapia , Probióticos/uso terapêutico , Uremia/induzido quimicamente , Uremia/terapia , Toxinas Urêmicas/toxicidade , Adulto , Idoso , Idoso de 80 Anos ou mais , Terapias Complementares/métodos , Dietoterapia/métodos , Suplementos Nutricionais , Feminino , Humanos , Nefropatias/fisiopatologia , Masculino , Pessoa de Meia-Idade , Terapia de Substituição Renal/métodos
4.
J Appl Toxicol ; 41(9): 1446-1455, 2021 09.
Artigo em Inglês | MEDLINE | ID: mdl-33458837

RESUMO

Recently, the Klotho protein (Klotho) has received substantial attention as protective factor against cardiovascular complications of chronic kidney disease (CKD). However, the direct effect and mechanism of Klotho on endothelial cells injury are not well-known. In this study, we incubated human vein umbilical endothelial cells (HUVECs) with uremic toxin indoxyl sulfate (IS) to mimic CKD internal environment and investigated the direct effect of Klotho on the HUVECs injury induced by IS and to explore the mechanism in this process. We found IS inhibited cell viability, increased endoplasmic reticulum stress, and mediated apoptosis of HUVECs. Treatment with Klotho significantly attenuated IS-induced above effects. Furthermore, Klotho alleviated the IS toxic effect on HUVECs via promoting AMP-activated protein kinase (AMPK) α1 phosphorylation instead of directly upregulating AMPKα1, which could be partly blocked by AMPK pathway inhibitor-Compound C. In addition, Klotho also inhibited intercellular adhesion molecule-1 (ICAM-1) and vascular cell adhesion molecule-1 (VCAM-1) expression induced by IS. Altogether, these results indicated that Klotho can protect HUVECs from IS-induced injury by alleviating AMPKα1-mediated endoplasmic reticulum stress.


Assuntos
Proteínas Quinases Ativadas por AMP/efeitos dos fármacos , Estresse do Retículo Endoplasmático/efeitos dos fármacos , Células Endoteliais da Veia Umbilical Humana/efeitos dos fármacos , Indicã/toxicidade , Proteínas Klotho/metabolismo , Toxinas Urêmicas/toxicidade , Proteínas Quinases Ativadas por AMP/antagonistas & inibidores , Apoptose/efeitos dos fármacos , Sobrevivência Celular/efeitos dos fármacos , Chaperona BiP do Retículo Endoplasmático/metabolismo , Inibidores Enzimáticos/farmacologia , Humanos , Molécula 1 de Adesão Intercelular/efeitos dos fármacos , RNA Interferente Pequeno/farmacologia , Insuficiência Renal Crônica/metabolismo , Fator de Transcrição CHOP/metabolismo , Molécula 1 de Adesão de Célula Vascular/efeitos dos fármacos
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