title: Oxidative stress and modification of renal vascular permeability are associated with acute kidney injury during P. berghei ANKA infection.
abstract: Malaria associated-acute kidney injury (AKI) is associated with 45% of mortality in adult patients hospitalized with severe form of the disease. However, the causes that lead to a framework of malaria-associated AKI are still poorly characterized. Some clinical studies speculate that oxidative stress products, a characteristic of Plasmodium infection, as well as proinflammatory response induced by the parasite are involved in its pathophysiology. Therefore, we aimed to investigate the development of malaria-associated AKI during infection by P. berghei ANKA, with special attention to the role played by the inflammatory response and the involvement of oxidative stress. For that, we took advantage of an experimental model of severe malaria that showed significant changes in the renal pathophysiology to investigate the role of malaria infection in the renal microvascular permeability and tissue injury. Therefore, BALB/c mice were infected with P. berghei ANKA. To assess renal function, creatinine, blood urea nitrogen, and ratio of proteinuria and creatininuria were evaluated. The products of oxidative stress, as well as cytokine profile were quantified in plasma and renal tissue. The change of renal microvascular permeability, tissue hypoxia and cellular apoptosis were also evaluated. Parasite infection resulted in renal dysfunction. Furthermore, we observed increased expression of adhesion molecule, proinflammatory cytokines and products of oxidative stress, associated with a decrease mRNA expression of HO-1 in kidney tissue of infected mice. The measurement of lipoprotein oxidizability also showed a significant increase in plasma of infected animals. Together, our findings support the idea that products of oxidative stress, as well as the immune response against the parasite are crucial to changes in kidney architecture and microvascular endothelial permeability of BALB/c mice infected with P. berghei ANKA.
authors.affiliation: Disciplina de Nefrologia, Departamento de Medicina, Universidade Federal de São Paulo, São Paulo, Brazil.
authors.forename: Rosa Maria
authors.initials: RM
authors.lastname: Elias
authors.forename: Matheus
authors.initials: M
authors.lastname: Correa-Costa
authors.forename: Claudiene Rodrigues
authors.initials: CR
authors.lastname: Barreto
authors.forename: Reinaldo Correia
authors.initials: RC
authors.lastname: Silva
authors.forename: Caroline Y
authors.initials: CY
authors.lastname: Hayashida
authors.forename: Angela
authors.initials: A
authors.lastname: Castoldi
authors.forename: Giselle Martins
authors.initials: GM
authors.lastname: Gonçalves
authors.forename: Tarcio Teodoro
authors.initials: TT
authors.lastname: Braga
authors.forename: Renato
authors.initials: R
authors.lastname: Barboza
authors.forename: Francisco José
authors.initials: FJ
authors.lastname: Rios
authors.forename: Alexandre Castro
authors.initials: AC
authors.lastname: Keller
authors.forename: Marcos Antonio
authors.initials: MA
authors.lastname: Cenedeze
authors.forename: Meire Ioshie
authors.initials: MI
authors.lastname: Hyane
authors.forename: Maria Regina
authors.initials: MR
authors.lastname: D'Império-Lima
authors.forename: Antônio Martins
authors.initials: AM
authors.lastname: Figueiredo-Neto
authors.forename: Marlene Antônia
authors.initials: MA
authors.lastname: Reis
authors.forename: Cláudio Romero Farias
authors.initials: CR
authors.lastname: Marinho
authors.forename: Alvaro
authors.initials: A
authors.lastname: Pacheco-Silva
authors.forename: Niels Olsen Saraiva
authors.initials: NO
authors.lastname: Câmara
mesh_terms: D058186:Acute Kidney Injury / Q000150:complications* / Q000378:metabolism* / Q000473:pathology; D000818:Animals; D017209:Apoptosis; D002199:Capillary Permeability; D002448:Cell Adhesion; D015687:Cell Hypoxia; D042783:Endothelial Cells / Q000469:parasitology / Q000473:pathology; D004912:Erythrocytes / Q000469:parasitology / Q000473:pathology; D006418:Heme / Q000378:metabolism; D007249:Inflammation / Q000150:complications; D007668:Kidney / Q000098:blood supply / Q000378:metabolism* / Q000469:parasitology / Q000473:pathology; D008288:Malaria / Q000150:complications*; D051379:Mice; D008807:Mice, Inbred BALB C; D018384:Oxidative Stress; D010962:Plasmodium berghei / Q000472:pathogenicity*; D017382:Reactive Oxygen Species / Q000378:metabolism
chemical_list: D017382:Reactive Oxygen Species; D006418:Heme