LUZIA NAOKO SHINOHARA FURUKAWA
Projetos de Pesquisa
Unidades Organizacionais
Departamento de Clínica Médica, Faculdade de Medicina
LIM/16 - Laboratório de Fisiopatologia Renal, Hospital das Clínicas, Faculdade de Medicina
LIM/16 - Laboratório de Fisiopatologia Renal, Hospital das Clínicas, Faculdade de Medicina
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conferenceObject Chronic Kidney Disease-Associated Frailty is characterized by changes in Muscular Expression of RANKL and FNDC5, which are partially reverted after Parathyroidectomy(2023) DUQUE, Eduardo J.; CRISPILHO, Shirley; OLIVEIRA, Ivone B.; REIS, Luciene M. dos; FURUKAWA, Luzia; TAKAYAMA, Liliam; PEREIRA, Rosa M.; SHINJO, Samuel K.; AVESANI, Carla; JORGETTI, Vanda; ELIAS, Rosilene M.; MOYSES, Rosa M.- Advanced Glycation End Products and Bone Metabolism in Patients with Chronic Kidney Disease(2023) QUADROS, Kelcia R. S.; ROZA, Noemi A. V.; FRANCA, Renata A.; ESTEVES, Andre B. A.; BARRETO, Joaquim; DOMINGUEZ, Wagner V.; FURUKAWA, Luzia N. S.; CARAMORI, Jacqueline Teixeira; SPOSITO, Andrei C.; OLIVEIRA, Rodrigo Bueno deAdvanced glycation end products (AGEs) accumulation may be involved in the progression of CKD-bone disorders. We sought to determine the relationship between AGEs measured in the blood, skin, and bone with histomorphometry parameters, bone protein, gene expression, and serum biomarkers of bone metabolism in patients with CKD stages 3 to 5D patients. Serum levels of AGEs were estimated by pentosidine, glycated hemoglobin (A1c), and N-carboxymethyl lysine (CML). The accumulation of AGEs in the skin was estimated from skin autofluorescence (SAF). Bone AGEs accumulation and multiligand receptor for AGEs (RAGEs) expression were evaluated by immunohistochemistry; bone samples were used to evaluate protein and gene expression and histomorphometric analysis. Data are from 86 patients (age: 51 +/- 13 years; 60 [70%] on dialysis). Median serum levels of pentosidine, CML, A1c, and SAF were 71.6 pmol/mL, 15.2 ng/mL, 5.4%, and 3.05 arbitrary units, respectively. AGEs covered 3.92% of trabecular bone and 5.42% of the cortical bone surface, whereas RAGEs were expressed in 0.7% and 0.83% of trabecular and cortical bone surfaces, respectively. AGEs accumulation in bone was inversely related to serum receptor activator of NF-KB ligand/parathyroid hormone (PTH) ratio (R = -0.25; p = 0.03), and RAGE expression was negatively related to serum tartrate-resistant acid phosphatase-5b/PTH (R = -0.31; p = 0.01). Patients with higher AGEs accumulation presented decreased bone protein expression (sclerostin [1.96 (0.11-40.3) vs. 89.3 (2.88-401) ng/mg; p = 0.004]; Dickkopf-related protein 1 [0.064 (0.03-0.46) vs. 1.36 (0.39-5.87) ng/mg; p = 0.0001]; FGF-23 [1.07 (0.4-32.6) vs. 44.1 (6-162) ng/mg; p = 0.01]; and osteoprotegerin [0.16 (0.08-2.4) vs. 6.5 (1.1-23.7) ng/mg; p = 0.001]), upregulation of the p53 gene, and downregulation of Dickkopf-1 gene expression. Patients with high serum A1c levels presented greater cortical porosity and Mlt and reduced osteoblast surface/bone surface, eroded surface/bone surface, osteoclast surface/bone surface, mineral apposition rate, and adjusted area. Cortical thickness was negatively correlated with serum A1c (R = -0.28; p = 0.02) and pentosidine levels (R = -0.27; p = 0.02). AGEs accumulation in the bone of CKD patients was related to decreased bone protein expression, gene expression changes, and increased skeletal resistance to PTH; A1c and pentosidine levels were related to decreased cortical thickness; and A1c levels were related to increased cortical porosity and Mlt.
- N-Acetyl-l-Cysteine Ameliorations Renal Function Early After Renal Ischemia and Reperfusion; it is not Protective over a Long Term under a High-Sodium Diet in Rats(2023) PEREIRA, Rafael Canavel; ROMAO, Carolina Martinez; CORREA, Beatriz Santos Geoffroy; DOMINGUEZ, Wagner Vasques; FURUKAWA, Luzia Naoko ShinoharaObjective: To evaluate the early and late effects of N-acetyl-l-cysteine (NAC) treatment on renal ischemia and reperfusion (I/R) insult in adult Wistar rats influenced by chronic high sodium (HS) intake. Methods: Adult male Wistar rats (8 weeks of age) received an HS (8.0% NaCl) or normal sodium (NS; 1.3% NaCl) diet and NAC (600 mg/L) in drinking water or normal water. At 11 weeks of age, the rats underwent a renal I/R procedure. They followed for 10 weeks after I/R, at the 1st, 2nd, 4th, and 10th weeks, in which tail blood pressure (tBP) and renal function were evaluated. And renal renin gene expression was evaluated in the 10th week after I/R. Results: During the study, it was observed that the tBP remained consistently higher in the HS-I/R+water group compared to the NS-I/R+water group. However, in the early weeks following I/R (1st, 2nd, and 4th weeks), the tBP was lower in the HS-I/ R+NAC group than in the HS-I/R+water group. In the 10th week after I/R, the serum creatinine levels were higher in both the HS-I/R+NAC and NS-I/R+NAC groups compared to the HS-I/R+water and NS-I/R+water groups. Conversely, the creatinine clearance was higher in the HS-I/R+NAC group than in the HS-I/R+ group in the 2nd week following I/R. Additionally, the urinary protein levels were higher in the HS-I/R+NAC group than in the NS-I/R+NAC group in the 10th week after I/R. It was also observed that NAC treatment resulted in increased renal renin gene expression in the 10th week following I/R. Conclusions: After renal I/R in animals given HS, NAC treatment was initially effective in lowering blood pressure or increasing creatinine clearance. However, these positive effects did not persist over the long term, resulting in decreased kidney function and increased blood pressure. Furthermore, the renin-angiotensin-aldosterone system was increased by HS intake, and the benefits of the NS diet were less effective than those of the HS diet. Thus, NAC provides temporary protection only in the early stages following an insult.
- COVID-19: Understanding the impact of anti-hypertensive drugs and hydroxychloroquine on the ACE1 and ACE2 in lung and adipose tissue in SHR and WKY rats(2023) CORREA, Beatriz Santos Geoffroy; BARROS, Silvana de; VAZ, Julia Braga; PERES, Maria Angelica; UCHIYAMA, Mayara Klimuk; SILVA, Alexandre Alves da; FURUKAWA, Luzia Naoko ShinoharaHypertensive individuals taking anti-hypertensive drugs from renin-angiotensin system inhibitors may exhibit a more severe evolution of the disease when contracting the SARS-CoV-2 virus (COVID-19 disease) due to potential increases in ACE2 expression. The study investigated ACE1 and ACE2 axes and hydroxychloroquine in the lungs and adipose tissue of male and female normotensive Wistar Kyoto (WKY) and spontaneously hypertensive rats (SHRs). SHRs were treated with losartan (10 mg/kg/day) or captopril (10 mg/kg/day) for 14 days or 7 days with hydroxychloroquine (200 mg/kg/day) in drinking water. WKY rats were also treated for 7 days with hydroxychloroquine. Blood pressure (BP), protein, and mRNA expression of ACE1 and ACE2 were analyzed in serum, adipose, and lung tissues. Losartan and captopril reduced BP in both sexes in SHR, whereas hydroxychloroquine increased BP in WKY rats. Losartan reduced ACE2 in serum and lungs in both sexes and in adipose tissue of male SHRs. Captopril decreased ACE2 protein in the lung of females and in adipose tissue in both sexes of SHRs. Hydroxychloroquine decreased ACE1 and ACE2 proteins in the lungs in both sexes and adipose tissue in male SHRs. In female WKY rats, ACE2 protein was lower only in the lungs and adipose tissue. Losartan effectively inhibited ACE2 in male and captopril in female SHRs. Hydroxychloroquine inhibited ACE2 in male SHRs and female WKY rats. These results further our understanding of the ACE2 mechanism in patients under renin-angiotensin anti-hypertensive therapy and in many trials using hydroxychloroquine for COVID-19 treatment and potential sex differences in response to drug treatment.