Precocious obesity predisposes the development of more severe cisplatin-induced acute kidney injury in young adult mice

Precocious obesity predisposes the development of more severe cisplatin-induced acute kidney injury in young adult mice

Author Ribeiro, Rosemara Silva Autor UNIFESP Google Scholar
Passos, Clévia dos Santos Autor UNIFESP Google Scholar
Novaes, Antonio da Silva Autor UNIFESP Google Scholar
Maquigussa, Edgar Autor UNIFESP Google Scholar
Gloria, Maria Aparecida da Autor UNIFESP Google Scholar
Visona, Iria Autor UNIFESP Google Scholar
Ykuta, Olinda Autor UNIFESP Google Scholar
Oyama, Lila Missae Autor UNIFESP Google Scholar
Boim, Mirian Aparecida Autor UNIFESP Google Scholar
Abstract Obesity and its consequences can damage the kidney over time. However, less is known about the impact of developing overweight/obesity during childhood on the kidney in adulthood and the renal impact of a superimposed acute kidney injury (AKI). This study evaluated the effect of obesity induced by a high-fat diet initiated soon after weaning on the adult life of mice and their response to superimposed nephrotoxic effects of cisplatin. C57BL/6 post weaning mice (3 weeks old) were divided into a control group (CT, n = 12) and a high-fat diet group (HF, n = 12). After 9 weeks, animals were further divided into the following groups: CT, CT treated with a single dose of cisplatin (CTCis, 20 mg/kg, i.p.), HF and HF treated with cisplatin (HFCis). The HF group exhibited higher body weight gain compatible with a moderate obesity. Obese mice presented increased visceral adiposity, hyperkalemia, sodium retention, glomerular hyperfiltration and proteinuria, without any significant changes in blood pressure and glycemia. AKI induced by cisplatin was exacerbated in obese animals with a 92% reduction in the GFR versus a 31% decrease in the CTCis group

this sharp decline resulted in severely elevated serum creatinine and urea levels. Acute tubular necrosis induced by cisplatin was worsened in obese mice. The HFCis group exhibited robust systemic and intrarenal inflammation that was significantly higher than that in the CTCis group

the HFCis group also showed a higher degree of renal oxidative stress. In conclusion, the moderate degree of obesity induced shortly after weaning resulted in mild early renal alterations, however, obese young animals were prone to develop a much more severe AKI induced by cisplatin.
xmlui.dri2xhtml.METS-1.0.item-coverage San Francisco
Language English
Sponsor Conselho Nacional de Desenvolvimento Científico e Tecnológico (CNPq)
Fundação de Amparo à Pesquisa do Estado de São Paulo (FAPESP)
Coordenação de Aperfeiçoamento de Pessoal de Nível Superior (CAPES)
Fundação Oswaldo Ramos
Grant number CNPq: 470662/2013-1
Date 2017
Published in Plos One. San Francisco, v. 12, n. 3, p. -, 2017.
ISSN 1932-6203 (Sherpa/Romeo, impact factor)
Publisher Public Library Science
Extent -
Origin https://dx.doi.org/10.1371/journal.pone.0174721
Access rights Open access Open Access
Type Article
Web of Science ID WOS:000399174800078
URI https://repositorio.unifesp.br/handle/11600/54906

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