title: 5-Lypoxygenase products are involved in renal tubulointerstitial injury induced by albumin overload in proximal tubules in mice.
abstract: The role of albumin overload in proximal tubules (PT) in the development of tubulointerstitial injury and, consequently, in the progression of renal disease has become more relevant in recent years. Despite the importance of leukotrienes (LTs) in renal disease, little is known about their role in tubulointerstitial injury. The aim of the present work was to investigate the possible role of LTs on tubulointerstitial injury induced by albumin overload. An animal model of tubulointerstitial injury challenged by bovine serum albumin was developed in SV129 mice (wild-type) and 5-lipoxygenase-deficient mice (5-LO(-/-)). The changes in glomerular morphology and nestin expression observed in wild-type mice subjected to kidney insult were also observed in 5-LO(-/-) mice. The levels of urinary protein observed in the 5-LO(-/-) mice subjected or not to kidney insult were lower than those observed in respective wild-type mice. Furthermore, the increase in lactate dehydrogenase activity, a marker of tubule damage, observed in wild-type mice subjected to kidney insult did not occur in 5-LO(-/-) mice. LTB4 and LTD4, 5-LO products, decreased the uptake of albumin in LLC-PK1 cells, a well-characterized porcine PT cell line. This effect correlated with activation of protein kinase C and inhibition of protein kinase B. The level of proinflammatory cytokines, tumor necrosis factor-α and interleukin (IL)-6, increased in mice subjected to kidney insult but this effect was not modified in 5-LO(-/-) mice. However, 5-LO(-/-) mice subjected to kidney insult presented lower macrophage infiltration and higher levels of IL-10 than wild-type mice. Our results reveal that LTs have an important role in tubulointerstitial disease induced by albumin overload.
authors.affiliation: Instituto de Biofísica Carlos Chagas Filho, Universidade Federal do Rio de Janeiro, CCS, Rio de Janeiro, Rio de Janeiro, Brazil; Instituto Federal de Educação, Ciência e Tecnologia, Rio de Janeiro, Rio de Janeiro, Brazil.
authors.forename: Sharon Schilling
authors.initials: SS
authors.lastname: Landgraf
authors.affiliation: Instituto de Biofísica Carlos Chagas Filho, Universidade Federal do Rio de Janeiro, CCS, Rio de Janeiro, Rio de Janeiro, Brazil.
authors.forename: Leandro Souza
authors.initials: LS
authors.lastname: Silva
authors.affiliation: Instituto de Biofísica Carlos Chagas Filho, Universidade Federal do Rio de Janeiro, CCS, Rio de Janeiro, Rio de Janeiro, Brazil.
authors.forename: Diogo Barros
authors.initials: DB
authors.lastname: Peruchetti
authors.affiliation: Instituto de Biofísica Carlos Chagas Filho, Universidade Federal do Rio de Janeiro, CCS, Rio de Janeiro, Rio de Janeiro, Brazil.
authors.forename: Gabriela Modenesi
authors.initials: GM
authors.lastname: Sirtoli
authors.affiliation: Instituto de Biofísica Carlos Chagas Filho, Universidade Federal do Rio de Janeiro, CCS, Rio de Janeiro, Rio de Janeiro, Brazil.
authors.forename: Felipe
authors.initials: F
authors.lastname: Moraes-Santos
authors.affiliation: Instituto de Biofísica Carlos Chagas Filho, Universidade Federal do Rio de Janeiro, CCS, Rio de Janeiro, Rio de Janeiro, Brazil.
authors.forename: Viviane Gomes
authors.initials: VG
authors.lastname: Portella
authors.affiliation: Instituto de Biofísica Carlos Chagas Filho, Universidade Federal do Rio de Janeiro, CCS, Rio de Janeiro, Rio de Janeiro, Brazil.
authors.forename: João Luiz
authors.initials: JL
authors.lastname: Silva-Filho
authors.affiliation: Instituto de Biofísica Carlos Chagas Filho, Universidade Federal do Rio de Janeiro, CCS, Rio de Janeiro, Rio de Janeiro, Brazil.
authors.forename: Carla Silva
authors.initials: CS
authors.lastname: Pinheiro
authors.affiliation: Instituto de Biofísica Carlos Chagas Filho, Universidade Federal do Rio de Janeiro, CCS, Rio de Janeiro, Rio de Janeiro, Brazil.
authors.forename: Thiago Pereira
authors.initials: TP
authors.lastname: Abreu
authors.affiliation: Instituto de Ciências Biomédicas, Universidade Federal do Rio de Janeiro, CCS, Rio de Janeiro, Rio de Janeiro, Brazil.
authors.forename: Christina Maeda
authors.initials: CM
authors.lastname: Takiya
authors.affiliation: Instituto de Ciências Biomédicas, Universidade Federal do Rio de Janeiro, CCS, Rio de Janeiro, Rio de Janeiro, Brazil.
authors.forename: Claudia Farias
authors.initials: CF
authors.lastname: Benjamin
authors.affiliation: Instituto de Biofísica Carlos Chagas Filho, Universidade Federal do Rio de Janeiro, CCS, Rio de Janeiro, Rio de Janeiro, Brazil; Departamento de Fisiologia e Biofísica, Instituto Nacional de Pesquisa Translacional em Saúde e Ambiente na Região Amazônica, CCS, Rio de Janeiro, Rio de Janeiro, Brazil.
authors.forename: Ana Acacia Sá
authors.initials: AA
authors.lastname: Pinheiro
authors.affiliation: Instituto de Biofísica Carlos Chagas Filho, Universidade Federal do Rio de Janeiro, CCS, Rio de Janeiro, Rio de Janeiro, Brazil.
authors.forename: Claudio
authors.initials: C
authors.lastname: Canetti
authors.affiliation: Instituto de Biofísica Carlos Chagas Filho, Universidade Federal do Rio de Janeiro, CCS, Rio de Janeiro, Rio de Janeiro, Brazil; Instituto Nacional de Ciência e Tecnologia em Biologia e Bioimagem, CCS, Rio de Janeiro, Rio de Janeiro, Brazil.
authors.forename: Celso
authors.initials: C
authors.lastname: Caruso-Neves
mesh_terms: D000818:Animals; D001094:Arachidonate 5-Lipoxygenase / Q000235:genetics / Q000378:metabolism*; D002417:Cattle; D002460:Cell Line; D004195:Disease Models, Animal; D017353:Gene Deletion; D007674:Kidney Diseases / Q000209:etiology* / Q000235:genetics / Q000378:metabolism* / Q000473:pathology; D007678:Kidney Glomerulus / Q000378:metabolism / Q000473:pathology; D007687:Kidney Tubules, Proximal / Q000378:metabolism / Q000473:pathology*; D008297:Male; D051379:Mice; D011507:Proteinuria / Q000150:complications* / Q000235:genetics / Q000378:metabolism*; D012709:Serum Albumin / Q000378:metabolism*; D013552:Swine
chemical_list: D012709:Serum Albumin; D001094:Arachidonate 5-Lipoxygenase