The biological roles of urea: A review of preclinical studies

Adeyomoye, OlorunsolaI; Akintayo, ChristopherO; Omotuyi, KoladeP; Adewumi, AdebukolaN

doi:10.4103/ijn.ijn_88_21

Cited by 7 publications

(6 citation statements)

References 62 publications

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“…3, the urea level on day 4 of cesium chloride poisoning was 7.01 ± 0.61 mmol/L, which is 14.3% higher than in the control group. On the 24th day of the study, the blood urea level increased by 31.3% compared to the control value, which may indicate an increase in protein breakdown processes (increased thermogenesis, febrile intoxication syndrome, hepatic decompensation), as well as the development of renal failure as a result of cesium nephrotoxicity (Adeyomoye at al., 2022). The results of the study of creatinine content showed that in the experi-mental group on day 4 of the experiment, its level increased by 1.9 times, and on day 24 by 2.64 times.…”

Section: Discussionmentioning

confidence: 99%

Ecological and toxicological features of the effect of stable cesium on striated muscle tissue (myocardium and skeletal muscles) of mammals

Yermishev

2023

Regul. Mech. Biosyst.

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Recently, the risks of radiation danger have significantly increased. This is connected with the start of a full-scale war against Ukraine and the seizure of the Zaporizhzhya NPP by the Russian Federation, which has the second most powerful arsenal of nuclear weapons in the world. The majority of studies devoted to the effect of radioactive radiation on the human body and animals absolutely do not take into account the ecotoxic effect of the carrier and a chemical element. At the same time, the body does not distinguish between radioactive and non-radioactive isotopes of chemical elements and interacts with them during exchange processes. The aim of the work was to study the influence of stable cesium on the microscopic structure of striated muscle tissue, both skeletal and cardiac ones. The results of our research revealed that intensive accumulation of cesium for 24 days occurred in all the examined organs and tissues. In fact, the most intensive accumulative process appeared to be in the heart by 214.9 times and by 695.3 times with skeletal muscles, with a simultaneous decrease in potassium content by 19.2% and 29.1%, respectively, compared to intact rats. We can talk about the presence of two mechanisms of action of cesium on tissues, including striated muscles: as an antagonist of potassium, which concerns the transport system of the latter and as a toxic element that initiates peroxide processes with subsequent modification of membranes and their potassium channels. Functional disturbances in the work of potassium channels of excitable tissues in the repolarization phase occur in the conditions of an increase in intracellular cesium in striated muscles. These disorders can proceed according to the type of acquired "potassium" channelopathies, which in the myocardium can manifest in the form of rhythm disorders, prolonged QT syndrome, etc. This leads to the appearance of significant violations of the histological structure of the examined tissues. Cesium has pronounced damaging effects on both skeletal and cardiac striated muscle tissue, with morphological changes in skeletal and cardiac striated muscle tissue being generally similar. Dystrophic changes in the nuclei and cytoplasm of cardiomyocytes and striated muscles, signs of impaired blood circulation in the microcirculatory channel with the formation of vascular wall edema, destruction of endothelial cells, various types of hemorrhages and lymphohistiocytic infiltration of the stroma of fibers are the consequences of the toxic effect of cesium on tissues. Thus, the results of changes in the histological structure of striated muscles under the action of cesium chloride obtained by us indicate a fairly high cytocidal activity of stable cesium.

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Section: Discussionmentioning

confidence: 99%

Ecological and toxicological features of the effect of stable cesium on striated muscle tissue (myocardium and skeletal muscles) of mammals

Yermishev

2023

Regul. Mech. Biosyst.

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“…15 The biological activity of urea has not been fully investigated. 15 However, some researchers have proven that urea and thiourea can interact with proteins to inhibit their aggregation. 11,12,16,17 They have specifically demonstrated a chaotropic effect via disintegrating inter-and intramolecular noncovalent interactions.…”

Section: ■ Introductionmentioning

confidence: 99%

“…Several other researchers have been working on the discovery of small molecular scaffolds based on sulfonyls, sulfonamides, , triazoles, thiadiazoles, ureas, , amines, , or aminoindoles, , to impede the formation of oligomers. Urea is a stable hydrophilic functional moiety that is used to convert and store nitrogenous waste in the terrestrial animal body as a metabolic byproduct until excreted . The biological activity of urea has not been fully investigated .…”

Section: Introductionmentioning

confidence: 99%

“…Urea is a stable hydrophilic functional moiety that is used to convert and store nitrogenous waste in the terrestrial animal body as a metabolic byproduct until excreted . The biological activity of urea has not been fully investigated . However, some researchers have proven that urea and thiourea can interact with proteins to inhibit their aggregation. ,,, They have specifically demonstrated a chaotropic effect via disintegrating inter- and intramolecular noncovalent interactions …”

Section: Introductionmentioning

confidence: 99%

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1,4-Diurea- and 1,4-Dithiourea-Substituted Aromatic Derivatives Selectively Inhibit α-Synuclein Oligomer Formation In Vitro

Ganegamage,

Ramirez,

Alnakhala

et al. 2023

ACS Omega

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Parkinson's disease (PD) is the second most common neurodegenerative disease, affecting the elderly population worldwide. In PD, the misfolding of α-synuclein (α-syn) results in the formation of inclusions referred to as Lewy bodies (LB) in midbrain neurons of the substantia nigra and other specific brain localizations, which is associated with neurodegeneration. There are no approved strategies to reduce the formation of LB in the neurons of patients with PD. Our drug discovery program focuses on the synthesis of urea and thiourea compounds coupled with aminoindole moieties to abrogate α-syn aggregation and to slow down the progression of PD. We synthesized several urea and thiourea analogues with a central 1,4-phenyl diurea/thiourea linkage and evaluated their effectiveness in reducing α-syn aggregation with a special focus on the selective inhibition of oligomer formation among other proteins. We utilized biophysical methods such as thioflavin T (ThT) fluorescence assays, transmission electron microscopy (TEM), photoinduced cross-linking of unmodified proteins (PICUP), as well as M17D intracellular inclusion cell-based assays to evaluate the antiaggregation properties and cellular protection of our best compounds. Our results identified compound 1 as the best compound in reducing α-syn fibril formation via ThT assays. The antioligomer formation of compound 1 was subsequently superseded by compound 2. Both compounds selectively curtailed the oligomer formation of α-syn but not tau 4R isoforms (0N4R, 2N4R) or p-tau (isoform 1N4R). Compounds 1 and 2 failed to abrogate tau 0N3R fibril formation by ThT and atomic force microscopy. Compound 2 was best at reducing the formation of recombinant α-syn fibrils by TEM. In contrast to compound 2, compound 1 reduced the formation of α-syn inclusions in M17D neuroblastoma cells in a dose-dependent manner. Compound 1 may provide molecular scaffolds for the optimization of symmetric molecules for its α-syn antiaggregation activity with potential therapeutic applications and development of small molecules in PD.

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“…El estudio de la función renal se apoya con el uso de indicadores tales como Nitrógeno Ureico en Sangre (BUN), Urea, Creatinina Sérica (CrS) junto con valores de Tasa de Filtrado Glomerular (TFG), ya que, con el consumo excesivo de proteínas, se genera una producción alta de Urea que se filtra por los riñones y mantiene los niveles sanguíneos entre 12.00 a 54.00 mg/dL. Esto permite monitorear si el aclaramiento de la sustancia es adecuado y no ocurren defectos en el filtrado glomerular que aumenten sus niveles (Adeyomoye et al, 2022). La relación BUN:Creatinina se usa para diferenciar causas de daño renal agudo; a nivel prerrenal por disminución de la perfusión renal o daños intrarrenales incidentes en la nefrona.…”

Section: Introductionunclassified

Identificación de Factores Asociados a la Ingesta Proteica Incidentes Sobre Función Renal en Deportistas de CrossFit®

González-González,

Rodriguez-Villa,

Fajardo Robledo

et al. 2023

ESJ

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Para aumentar la masa muscular, el CrossFit® ha sido relevante a la hora de ofrecer un ejercicio hipertrófico, aunque, el requerimiento proteico a consumir puede transformarse en excesivo. Las funciones renales activadas por la cantidad de metabolitos de degradación de proteínas se han asociado con procesos que desencadenan alteraciones renales. OBJETIVO: Identificar si el perfil de consumo proteico en deportistas de CrossFit® incide sobre la función renal. MATERIAL Y MÉTODO: En un período de cuatro meses, se registró el peso, altura, índice de masa corporal; dieta e información de suplementación proteica de 27 deportistas de CrossFit® voluntarios (23 hombres, 4 mujeres; edad promedio: 28.20 ± 3.60 años) en "Distrito Crossfit" (Jalisco, México). Se solicitaron estudios de Nitrógeno Ureico en Sangre, Urea y Creatinina Sérica, en "Salud Digna" (Jalisco, México), para determinar la tasa de filtración glomerular, con las fórmulas de Cockcroft-Gault, Modification of Diet in Renal Disease-4 y Mawer. Se compararon grupos de consumo alto versus normal por g/kg/d y mayor y menor consumo de 236.00 g/día, considerando la cantidad requerida para aumentar la masa muscular. RESULTADOS: Existieron disminuciones significativas (p<0.050) en la tasa de filtración glomerular con un alto consumo de 236.00 g/día y hubo un aumento significativo (p<0.050) de creatinina sérica en la suplementación durante más de un año, con una ingesta aumentada de 236.00 g/día, en comparación con aquellos con una ingesta adecuada sin suplementación. CONCLUSIÓN: El factor relevante para generar un efecto significativo en la filtración glomerular, es la cantidad y el tiempo de consumo de proteínas. To increase muscle mass, CrossFit® has been relevant in offering hypertrophic exercise, although the protein requirement to be consumed may become excessive. Renal functions activated by the amount of protein degradation metabolites have been associated with processes that trigger renal alterations. OBJECTIVE: To identify whether the protein intake profile in CrossFit® athletes affects renal function. MATERIALS AND METHODS: Over a period of four months, the weight, height, body mass index, diet, and protein supplementation information of 27 volunteer CrossFit® athletes (23 men, 4 women; average age: 28.20 ± 3.60 years) was recorded at "Distrito Crossfit" (Jalisco, México). Blood Urea Nitrogen, Urea, and Serum Creatinine studies were requested at "Salud Digna" (Jalisco, México) to determine glomerular filtration rate, with the Cockcroft-Gault, Modification of Diet in Renal Disease-4 and Mawer formulas. High versus normal intake groups were compared by g/kg/d and a higher and lower intake of 236.00 g/day, considering the amount required to increase muscle mass. RESULTS: There was a significant decrease (p<0.050) in the glomerular filtration rate with high a intake of 236.00 g/day and there was a significant increase (p<0.050) in serum creatinine on supplementation for more than one year with increased intake of 236.00 g/day compared to those with adequate intake without supplementation. CONCLUSION: The relevant factor to generate a significant effect on glomerular filtration is the amount and time of protein intake.

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The biological roles of urea: A review of preclinical studies

Cited by 7 publications

References 62 publications

Ecological and toxicological features of the effect of stable cesium on striated muscle tissue (myocardium and skeletal muscles) of mammals

Ecological and toxicological features of the effect of stable cesium on striated muscle tissue (myocardium and skeletal muscles) of mammals

1,4-Diurea- and 1,4-Dithiourea-Substituted Aromatic Derivatives Selectively Inhibit α-Synuclein Oligomer Formation In Vitro

Identificación de Factores Asociados a la Ingesta Proteica Incidentes Sobre Función Renal en Deportistas de CrossFit®

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