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1.
Biochem Pharmacol ; 194: 114804, 2021 12.
Article in English | MEDLINE | ID: mdl-34678223

ABSTRACT

During ischemic acute kidney injury (AKI), loss of cytoskeletal integrity and disruption of intercellular junctions are rapid events in response to ATP depletion. Angiotensin II type 2 receptor (AT2R) is overexpressed in injury situations and its stimulation by angiotensin II (AngII) is related to beneficial renal effects. Its role on ischemic AKI has not been deeply studied. The aim of the present study was to investigate whether pretreatment with the AT2R agonist, C21, prevents ischemic renal epithelial cell injury. Studies in a model of 40 min of renal ischemia followed by 24 h of reperfusion (IR) in rats demonstrated that C21 pretreatment attenuated renal dysfunction and induced better preservation of tubular architecture. In addition, we studied the expression of Rho GTPases, RhoA and Cdc42, since they are key proteins in the regulation of the actin cytoskeleton and the stability of epithelial intercellular junctions. IR downregulated RhoA and Cdc42 abundance in rat kidneys. C21 pretreatment prevented RhoA reduction and increased Cdc42 abundance compared to controls. We also used an in vitro model of ATP depletion in MDCK cells grown on filter support. Using immunofluorescence we observed that in MDCK cells, C21 pretreatment prevented the ATP depletion-induced reduction of actin in brush border microvilli and in stress fibers. Moreover, C21 prevented membrane E-cadherin reduction, and RhoA and Cdc42 downregulation. The present study describes for the first time a renoprotective effect of the AT2R agonist, C21, against AKI, and provides evidence supporting that stimulation of AT2R triggers cytoprotective mechanisms against an ischemic event.


Subject(s)
Acute Kidney Injury/prevention & control , Anti-Inflammatory Agents/therapeutic use , Imidazoles/therapeutic use , Kidney Tubules/drug effects , Receptor, Angiotensin, Type 2/agonists , Sulfonamides/therapeutic use , Thiophenes/therapeutic use , Urothelium/drug effects , Acute Kidney Injury/metabolism , Acute Kidney Injury/pathology , Animals , Anti-Inflammatory Agents/pharmacology , Dogs , Dose-Response Relationship, Drug , Imidazoles/pharmacology , Ischemia/drug therapy , Ischemia/metabolism , Ischemia/pathology , Kidney/drug effects , Kidney/metabolism , Kidney/pathology , Kidney Tubules/metabolism , Kidney Tubules/pathology , Madin Darby Canine Kidney Cells , Male , Rats , Rats, Wistar , Receptor, Angiotensin, Type 2/metabolism , Sulfonamides/pharmacology , Thiophenes/pharmacology , Urothelium/metabolism , Urothelium/pathology
2.
Rev. esp. nutr. comunitaria ; 16(3): 120-127, jul.-sept. 2010. tab, ilus
Article in Spanish | IBECS | ID: ibc-85241

ABSTRACT

Fundamento: El pescado de mar es fuente de AG omega-3 (AGO3). La ingesta de AGO3 ha mostrado disminuir la producción de derivados del ácido araquidónico con actividad inflamatoria, aumentar los valores de derivados del ácido eicosapentaenoico de menor actividad e inhibir linfocitos T helper-2 mediadores de reacciones inflamatorias alérgicas. Por otro lado, el pescado de mar es un importante alérgeno alimentario y también puede actuar como alimento liberador de histamina. El objetivo de este trabajo es evaluar la relación entre el consumo de pescado de mar y los síntomas de enfermedades alérgicas. Métodos: Este estudio transversal se realizó en 765 alumnos (el 83,4%, mujeres) elegidos al azar de la Universidad del Centro Educativo Latinoamericano, con edades entre 17 y 65 años, mediante cuestionarios validados para enfermedades alérgicas e ingesta de pescado de mar. Resultados: Quienes consumían pescado de mar una o más veces al mes, semanal o diario (46,7%), presentaron prevalencia de síntomas de asma del 8% en el último año, mientras que en los que nunca lo consumían o lo hacían menos frecuentemente fue del 12,9% (p < 0,05). Esto mismo ocurrió con síntomas de asma por ejercicio (el 7,9 frente al 12,2%; p < 0,05), tos seca nocturna no asociada a infecciones (el 13,3 frente al 19,6%; p < 0,05) y rinoconjuntivitis alérgica en el último año (el 20,8 frente al 27,5%; p < 0,05) y con síntomas de ambas enfermedades alérgicas respiratorias (el 4,2 frente al 8,7%; p < 0,005). Se mantuvo la significación estadística al estratificar por sexo, edad, obesidad, reflujo y hábito de fumar. También hubo mayor frecuencia de síntomas de urticaria en individuos que consumían pescado de mar más de dos veces a la semana (el 29,5 frente al 12,5%; p < 0,05). Conclusiones: Los resultados señalan que el consumo mensual de pescado de mar podría proteger, por su contenido de AGO3, contra enfermedades como asma y rinoconjuntivitis alérgica. Sin embargo, consumos elevados incrementarían la frecuencia de urticaria, probablemente en relación con fenómenos alérgicos o seudoalérgicos(AU)


Background: Sea fish (SF) is a natural source of omega-3 fatty acids (O3FA). Intake of O3FA reduces the production of arachidonic acid derivatives, which have antiinflammatory activity, and elevates levels of eicosapentaenoic acid derivatives, with lower activity. O3FA also inhibit T helper-2 lymphocytes, which mediate allergic inflammatory reactions. SF is a major food allergen and could also act as a histamine-releasing food. The objective of this study was to analyze the association between SF consumption and the presence of allergic symptoms. Methods: We conducted a cross-sectional study in 765 randomly selected students (83.4% women), aged 17-65 years old, attending the Universidad del Centro Educativo Latinoamericano. The students completed validated questionnaires on allergic diseases and the frequency of SF intake. Results: The prevalence of asthma symptoms in the previous 12 months was 8.0% among participants reporting SF consumption daily, weekly or once a month or more (46.7%) and was 12.9% in those reporting SF consumption less than once a month or never (p<0.05). Similar results were obtained when we evaluated exercise-induced asthma (7.9% vs 12.2%; p<0.05), nocturnal dry cough not associated with infections (13.3% vs 19.6%; p<0.05), allergic rhinoconjunctivitis in the last year (20.8% vs 27.5%; p<0.05) and symptoms of both allergic respiratory diseases (4.2% vs 8.7%; p<0.005). Statistical significance was maintained when stratification by sex, age, obesity, reflux and smoking habits was performed. In contrast, a higher frequency of urticaria symptoms was found in participants who reported SF consumption more than twice a week (29.5% vs 12.5%; p<0.05). Conclusions: These data suggest that SF consumption at least once a month could protect against diseases such as asthma and allergic rhinoconjunctivitis, due to the O3FA content of SF. However, high SF intake could increase the prevalence of urticaria, probably because of allergic or pseudoallergic phenomena(AU)


Subject(s)
Humans , Male , Female , Adolescent , Adult , Middle Aged , Food Hypersensitivity/epidemiology , Fish Products/adverse effects , Urticaria/complications , Urticaria/diagnosis , Gastroesophageal Reflux/complications , Gastroesophageal Reflux/diagnosis , Cross-Sectional Studies , Surveys and Questionnaires , 28599 , Confidence Intervals
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