Navegando por Palavras-chave "Acute renal injury"

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    Annexin A1 protein attenuates cyclosporine-induced renal hemodynamics changes and macrophage infiltration in rats
    (Springer, 2012-03-01) Araujo, Leandro Pires [UNIFESP]; Truzzi, Renata Ramos; Florido Mendes, Gloria Elisa; Mendes Luz, Marcus Alexandre; Burdmann, Emmanuel A.; Oliani, Sonia Maria [UNIFESP]; São Paulo State Univ UNESP; Universidade Federal de São Paulo (UNIFESP); Sao Jose do Rio Preto Med Sch; Universidade de São Paulo (USP)
    Cyclosporine (CsA) remains an important immunosuppressant for transplantation and for treatment of autoimmune diseases. the most troublesome side effect of CsA is renal injury. Acute CsA-induced nephrotoxicity is characterized by reduced renal blood flow (RBF) and glomerular filtration rate (GFR) due to afferent arteriole vasoconstriction. Annexin A1 (ANXA1) is a potent anti-inflammatory protein with protective effect in renal ischemia/reperfusion injury. Here we study the effects of ANXA1 treatment in an experimental model of acute CsA nephrotoxicity.Salt-depleted rats were randomized to treatment with VH (vehicles 1 mL/kg body weight/day), ANXA1 (Ac2-26 peptide 1 mg/kg body weight/day intraperitoneally), CsA (20 mg/kg body weight/day subcutaneously) and CsA + ANXA1 (combination) for seven days. We compared renal function and hemodynamics, renal histopathology, renal tissue macrophage infiltration and renal ANXA1 expression between the four groups.CsA significantly impaired GFR and RBF, caused tubular dilation and macrophage infiltration and increased ANXA1 renal tissue expression. Treatment with ANXA1 attenuated CSA-induced hemodynamic changes, tubular injury and macrophage infiltration.ANXA1 treatment attenuated renal hemodynamic injury and inflammation in an acute CsA nephrotoxicity model.
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    Avaliação da heme oxigenase 1 no pré-condicionamento nefrotóxico in vivo e in vitro
    (Universidade Federal de São Paulo (UNIFESP), 2018-01-29) Silva, Fernanda Duarte da [UNIFESP]; Borges, Fernanda Teixeira [UNIFESP]; Schor, Nestor [UNIFESP]; http://lattes.cnpq.br/8276708741672261; http://lattes.cnpq.br/4206613998602417; http://lattes.cnpq.br/9589233931342849
    Nephrotoxicity is one of the major side effects of aminoglycoside antibiotics such as Gentamicin (Genta). Preconditioning (PC) refers to the situation in which an organ or tissue subjected to an aggression acquires resistance or responds less intensely when a new aggression is repeated. The mechanism of CP is well studied, it is believed that mechanisms such as increased activity of antioxidant enzymes such as Hemeoxygenase 1 (HO1) may be involved. Objective: To study the participation of Heme oxygenase 1 (HO1) and the nephroprotective effect of PC induced by Genta in vivo and in vitro. Methods In vivo: Wistar rats were divided into Control (CTL), Genta treated animals for 10 consecutive days (IU), animals treated with Genta and Hemin for 10 consecutive days (IU + HEMIN), animals preconditioned with Genta ID) and animals preconditioned with Genta and treated concomitantly with Hemin (ID + HEMIN). Blood and urine samples were collected before and after treatment (groups IU and IU + HEMIN) and postCP (ID and ID + HEMIN groups) for analysis of creatinine, urea, sodium excretion fraction, urinary peroxides, lipid peroxidation, protein carbonylated, plasma antioxidant fraction, enzymatic activity (SOD and CAT). Animals were sacrificed and kidneys removed for immunohistochemistry for SOD and CAT. Methods In vitro: Human proximal tubule (HK2) cells were subdivided into control (CTL) groups, treated with Genta for 24h (IU), cells treated with Genta and the HO1 inducer for 24hs (IU + HEMIN). cells treated with Genta and the HO1 inhibitor for 24h concomitantly (IU + ZNPP), cells preconditioned with Genta and exposed to the antibiotic after 9 days (ID), Insulto double associated with the inducer of HO1 (ID + HEMIN ) and double insult associated with the HO1 inhibitor (ID + ZNPP). Necrosis and apoptosis were evaluated, respectively, by the Acridine Orange / Etho Bromide and Hoescht 33342 dyes. The expression of HO1 was performed by Western Blot. Results: Rats treated with Genta for 10 consecutive days (UI) presented an increase in plasma creatinine, urea, proteinuria, and sodium excretion fraction, characterizing the Nephrotoxic AKI model. The PC (ID) protected the animals from increasing these parameters. We observed increased urinary, lipid peroxides and carbonylated protein in the UI group in relation to the CTL and PC (ID) group. Conversely we observed an increase in the antioxidant fraction of the plasma, as well as an increase in the immunostaining for antioxidant enzymes (superoxide dismutase1 and catalase) in the PC group in relation to the other groups. Interestingly, the HO1 (Hemin) inducer potentiated these effects. In the main target of Genta, the proximal tubular cell, PC inhibited cell death by antibioticinduced necrosis and apoptosis, and Hemin potentiated the protective effect of CP on viability. Conclusion: PC protected the animals from GENT induced by GENT and this effect was mediated by the inhibition of oxidative stress, by direct action in the proximal tubular cell and induction of antioxidant enzymes, such as HO1, which may be a potential alternative in treatment nephrotoxic ARF by aminoglycosides.
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    Obesidade induzida após o desmame potencializa o efeito nefrotóxico da cisplatina
    (Universidade Federal de São Paulo (UNIFESP), 2016-10-31) Ribeiro, Rosemara Silva [UNIFESP]; Boim, Mirian Aparecida [UNIFESP]; http://lattes.cnpq.br/8916858915652849; http://lattes.cnpq.br/6160112679243206; Universidade Federal de São Paulo (UNIFESP)
    Overweight establishes a charge on the kidney resulting in increased glomerular filtration rate (GFR) and renal hypertrophy may accelerate the damage of renal function. The renal effects of obesity in adult individual are well explored, less is known on the impact of childhood obesity in the kidney in adult life, and if this event can exacerbate the renal response to an acute injury. The objectives of this study were: evaluate the impact of the obesity established in mice during childhood on renal function in adult life and evaluate if metabolic condition potentiate the nephrotoxic effects of cisplatin. C57BL/6 mice at 21 days age (postweaning) were divided into group control (CT), fed with standard diet, and high fat diet group (HF), fed with high fat diet. After 9 weeks the animals were divided into groups: CT, CT treated with cisplatin (CTCis), HF and HF treated with cisplatin (HFCis). Cisplatin was administered in single dose of 20 mg/kg (i.p.). After 72 hours the animals were anesthetized and blood and tissues (kidneys and visceral fat) were used for biochemical, molecular and histology analysis. The HF group exhibited higher body weight gain, increased visceral adiposity, hyperkalemia, sodium retention, glomerular hyperfiltration, proteinuria and intrarenal overexpression of the pro oxidant enzyme, gp91phox, indicating renal function responses to the obesity. Cisplatin induced AKI with reduced GFR in both groups, but the effect was exacerbated in obese animals with reduction of 92% versus 31% in the CTCis group, resulting in an expressive serum creatinine and urea accumulation. The HFCis group exhibited systemic and intrarenal inflammation significantly higher than the non obese animals. These results suggest that obese animals were more susceptible to the nephrotoxic effects induced by cisplatin resulting in greater severity of AKI.