CAMILLA FANELLI
Projetos de Pesquisa
Unidades Organizacionais
Departamento de Clínica Médica, Faculdade de Medicina
LIM/29 - Laboratório de Nefrologia Celular, Genética e Molecular, Hospital das Clínicas, Faculdade de Medicina
LIM/29 - Laboratório de Nefrologia Celular, Genética e Molecular, Hospital das Clínicas, Faculdade de Medicina
9 resultados
Resultados de Busca
Agora exibindo 1 - 9 de 9
- Effects of losartan, in monotherapy or in association with hydrochlorothiazide, in chronic nephropathy resulting from losartan treatment during lactation(2011) FANELLI, C.; FERNANDES, B. H. V.; MACHADO, F. G.; OKABE, C.; MALHEIROS, D. M. A. C.; FUJIHARA, C. K.; ZATZ, R.Fanelli C, Fernandes BH, Machado FG, Okabe C, Malheiros DM, Fujihara CK, Zatz R. Effects of losartan, in monotherapy or in association with hydrochlorothiazide, in chronic nephropathy resulting from losartan treatment during lactation. Am J Physiol Renal Physiol 301: F580-F587, 2011. First published June 8, 2011; doi:10.1152/ajprenal.00042.2011.-We recently standardized a model (L(Lact)) of severe chronic kidney disease based on impaired nephrogenesis by suppression of angiotensin II activity during lactation (Machado FG, Poppi EP, Fanelli C, Malheiros DM, Zatz R, Fujihara CK. Am J Physiol Renal Physiol 294: F1345-F1353, 2008). In this new study of the L(Lact) model, we sought to gain further insight into renal injury mechanisms associated with this model and to verify whether the renoprotection obtained with the association of the angiotensin II receptor blocker losartan (L) and hydrochlorothiazide (H), which arrested renal injury in the remnant kidney model, would provide similar renoprotection. Twenty Munich-Wistar dams, each nursing six pups, were divided into control, untreated, and L(Lact) groups, given losartan (L; 250 mg.kg(-1).day(-1)) until weaning. The male LLact offspring remained untreated until 7 mo of age, when renal functional and structural parameters were studied in 17 of them, used as pretreatment control (L(Lact)Pre), and followed no further. The remaining rats were then divided among groups L(Lact) + V, untreated; L(Lact) + L, given L (50 mg.kg(-1).day(-1)) now as a therapy; L(Lact) + H, given H (6 mg.kg(-1).day(-1)); and L(Lact) + LH, given L and H. All parameters were reassessed 3 mo later in these groups and in age-matched controls. At this time, L(Lact) rats exhibited hypertension, severe albuminuria, glomerular damage, marked interstitial expansion/inflammation, enhanced cell proliferation, myofibroblast infiltration, and creatinine retention. L monotherapy normalized albuminuria and prevented hypertension and the progression of renal injury, inflammation, and myofibroblast infiltration. In contrast to the remnant model, the LH combination promoted only slight additional renoprotection, perhaps because of a limited tendency to retain sodium in L(Lact) rats.
conferenceObject SUBCAPSULAR INJECTION OF EXTRACELLULAR VESICLES FROM MESENCHYMAL STEM CELLS, PROMOTED ADDITIONAL RENOPROTECTION IN AN EXPERIMENTAL MODEL OF CKD(2023) NODA, Paloma; ORNELLAS, Felipe; CELESTRINO, Giovanna; TELES, Flavio; NORONHA, Irene L.; FANELLI, CamillaconferenceObject RENAL SUBCAPSULAR ADMINISTRATION OF ADIPOSE DERIVED MESENCHYMAL STEM CELLS PREVENTED THE PROGRESSION OF RENAL DAMAGE IN AN EXPERIMENTAL MODEL OF CKD(2020) CLARO, Marina P.; PEREIRA, Krislley R.; SILVA, Everidiene K. V. B.; TELES, Flavio; BARBOSA, Paulyana F.; NORONHA, Irene L.; FANELLI, Camilla- An association of losartan-hydrochlorothiazide, but not losartan-furosemide, completely arrests progressive injury in the remnant kidney(2016) ARIAS, Simone Costa Alarcon; SOUZA, Renata Alves; MALHEIROS, Denise Maria Avancini Costa; FANELLI, Camilla; FUJIHARA, Clarice Kazue; ZATZ, RobertoWe have previously shown that an association of losartan and hydrochlorothiazide, initiated 1 mo after 5/6 nephrectomy (Nx), reversed hypertension and albuminuria and promoted lasting renoprotection. In this new study, we investigated whether equal or even better protection could be obtained by combining losartan and furosemide. Nx was performed in 58 Munich-Wistar rats. One month later, tail-cuff pressure and albuminuria were markedly elevated. At this time, Nx rats were distributed among the following four groups: untreated Nx rats, Nx rats that received losartan, Nx rats that received losartan + hydrochlorothiazide, and Nx rats that received losartan + furosemide. Seven months later, Nx rats exhibited high mortality, severe hypertension, albuminuria, glomerulosclerosis, and interstitial fibrosis. Losartan treatment limited mortality and attenuated the renal and hemodynamic abnormalities associated with Nx. As previously shown, the losartan + hydrochlorothiazide association normalized tail-cuff pressure and albumin, prevented renal injury, and reduced mortality to zero. The losartan + furosemide treatment failed to reduce tail-cuff pressure or albumin to normal and prevented renal injury less efficiently than the losartan and hydrochlorothiazide regimen. The reasons for the differing efficacies of the losartan + furosemide and losartan + hydrochlorothiazide schemes are unclear and may include beneficial nondiuretic actions of thiazides, such as vasorelaxation and antiproliferative activity. These results refute the established concept that thiazides and thiazide-like diuretics are ineffective at advanced chronic kidney disease stages. Rather, they suggest that, in view of their renoprotective action, these compounds may even be preferable to loop diuretics in the management of hypertension in advanced chronic kidney disease.
- Chronic exposure to hypoxia attenuates renal injury and innate immunity activation in the remnant kidney model(2019) REMPEL, Lisienny Campoli Tono; FAUSTINO, Viviane Dias; FORESTO-NETO, Orestes; FANELLI, Camilla; ARIAS, Simone Costa Alarcon; MOREIRA, Gizely Cristina da Silva; NASCIMENTO, Thalita Fabiana; AVILA, Victor Ferreira; MALHEIROS, Denise Maria Avancini Costa; CAMARA, Niels Olsen Saraiva; FUJIHARA, Clarice Kazue; ZATZ, RobertoHypoxia is thought to influence the pathogenesis of chronic kidney disease, but direct evidence that prolonged exposure to tissue hypoxia initiates or aggravates chronic kidney disease is lacking. We tested this hypothesis by chronically exposing normal rats and rats with 5/6 nephrectomy (Nx) to hypoxia. In addition, we investigated whether such effect of hypoxia would involve activation of innate immunity. Adult male Munich-Wistar rats underwent Nx (n = 54) or sham surgery (sham; n = 52). Twenty-six sham rats and 26 Nx rats remained in normoxia, whereas 26 sham rats and 28 Nx rats were kept in a normobaric hypoxia chamber (12% O-2) for 8 wk. Hypoxia was confirmed by immunohistochemistry for pimonidazole. Hypoxia was confined to the medullary area in sham + normoxia rats and spread to the cortical area in sham + hypoxia rats, without changing the peritubular capillary density. Exposure to hypoxia promoted no renal injury or elevation of the content of IL-1 beta or Toll-like receptor 4 in sham rats. In Nx, hypoxia also extended to the cortical area without ameliorating the peritubular capillary rarefaction but, unexpectedly, attenuated hypertension, inflammation, innate immunity activation, renal injury, and oxidative stress. The present study, in disagreement with current concepts. shows evidence that hypoxia exerts a renoprotective effect in the Nx model instead of acting as a factor of renal injury. The mechanisms for this unexpected beneficial effect are unclear and may involve NF-kappa B inhibition, amelioration of oxidative stress, and limitation of angiotensin II production by the renal tissue.
conferenceObject THE ASSOCIATION OF TAMOXIFEN TO THE CONSERVATIVE CKD TREATMENT PROMOTED ADDITIONAL ANTIFIBROTIC EFFECTS IN A MODEL OF HYPERTENSIVE NEPHROSCLEROSIS(2023) FANELLI, Camilla; FRANCINI, Ana Laura Rubio; NODA, Paloma; IANNUZZI, Leandro; CELESTRINO, Giovanna; ORNELLAS, Felipe; NORONHA, Irene L.- NF-kappa B activation mediates crystal translocation and interstitial inflammation in adenine overload nephropathy(2013) OKABE, Cristiene; BORGES, Raquel Lerner; ALMEIDA, Danilo Candido de; FANELLI, Camilla; BARLETTE, Grasiela Pedreira; MACHADO, Flavia Gomes; ARIAS, Simone Costa Alarcon; MALHEIROS, Denise Maria Avancini Costa; CAMARA, Niels Olsen Saraiva; ZATZ, Roberto; FUJIHARA, Clarice KazueAdenine overload promotes intratubular crystal precipitation and interstitial nephritis. We showed recently that these abnormalities are strongly attenuated in mice knockout for Toll-like receptors-2, -4, MyD88, ASC, or caspase-1. We now investigated whether NF-kappa B activation also plays a pathogenic role in this model. Adult male Munich-Wistar rats were distributed among three groups: C (n = 17), receiving standard chow; ADE (n = 17), given adenine in the chow at 0.7% for 1 wk and 0.5% for 2 wk; and ADE + pyrrolidine dithiocarbamate (PDTC; n = 14), receiving adenine as above and the NF-kappa B inhibitor PDTC (120 mg.kg(-1).day(-1) in the drinking water). After 3 wk, widespread crystal deposition was seen in tubular lumina and in the renal interstitium, along with granuloma formation, collagen accumulation, intense tubulointerstitial proliferation, and increased interstitial expression of inflammatory mediators. Part of the crystals were segregated from tubular lumina by a newly formed cell layer and, at more advanced stages, appeared to be extruded to the interstitium. p65 nuclear translocation and IKK-alpha increased abundance indicated activation of the NF-kappa B system. PDTC treatment prevented p65 migration and normalized IKK-alpha, limited crystal shift to the interstitium, and strongly attenuated interstitial fibrosis/inflammation. These findings indicate that the complex inflammatory phenomena associated with this model depend, at least in part, on NF-kappa B activation, and suggest that the NF-kappa B system may become a therapeutic target in the treatment of chronic kidney disease.
conferenceObject INHIBITION OF THE TLR4/NF-kappa B AXIS ATTENUATED GLOMERULAR INFLAMMATION AND SCLEROSIS IN LONG TERM EXPERIMENTAL DIABETIC KIDNEY DISEASE(2018) FORESTO-NETO, Orestes; ALBINO, Amanda; ARIAS, Simone; FAUSTINO, Viviane; AVILA, Victor; SENA, Claudia; FANELLI, Camilla; VIANA, Vivian; CENEDEZE, Marcos; MACHADO, Flavia; MALHEIROS, Denise; CAMARA, Niels; FUJIHARA, Clarice; ZATZ, RobertoconferenceObject RENAL SUBCAPSULAR ADIPOSE-DERIVED MESENCHYMAL STEM CELLS (ASC) ADMINISTRATION, ASSOCIATED TO LOSARTAN TREATMENT, PREVENTED THE PROGRESSION OF RENAL DAMAGE IN AN EXPERIMENTAL MODEL OF CHRONIC KIDNEY DISEASE (CKD)(2020) CLARO, Marina P.; PEREIRA, Krislley R.; SILVA, Everidiene K. V. B.; TELES, Flavio; BARBOSA, Paulyana F.; NORONHA, Irene L.; FANELLI, Camilla