Physical Exercise Exacerbates Acute Kidney Injury Induced by LPS via Toll-Like Receptor 4

Author(s)

Rodrigues Hungaro, Talita Guerreiro ^[1] ; Freitas-Lima, Leandro Ceotto ^[2] ; Gregnani, Marcos Fernandes ^[2] ; Perilhao, Mauro Sergio ^[1] ; Alves-Silva, Thais ^[2] ; Arruda, Adriano Cleis ^[1] ; Barrera-Chimal, Jonatan ^{[3, 4]} ; Estrela, Gabriel Rufino ^[5] ; Carvalho Araujo, Ronaldo ^{[2, 1]}

Affiliation

^[1] Univ Fed Sao Paulo, Dept Biofis, Lab Genet & Metab Exercicio, Programa Nefrol, Sao Paulo - Brazil

^[2] Univ Fed Sao Paulo, Dept Biofis, Lab Genet & Metab Exercicio, Programa Biol Mol, Sao Paulo - Brazil

^[3] Univ Nacl Autonoma Mexico, Inst Invest Biomed, Mexico City, DF - Mexico

^[4] Inst Nacl Cardiol Ignacio Chavez, Unidad Invest UNAM INC, Mexico City, DF - Mexico

^[5] Univ Fed Sao Paulo, Dept Oncol Clin & Expt, Disciplina Hematol & Hematoterapia, Sao Paulo - Brazil

• Document type: Journal article
• Source: FRONTIERS IN PHYSIOLOGY; v. 11, JUL 17 2020.
• Web of Science Citations: 0

Abstract

Introduction:Lipopolysaccharide (LPS) is a systemic response-triggering endotoxin, which has the kidney as one of its first targets, thus causing acute injuries to this organ. Physical exercise is capable of promoting physiological alterations and modulating inflammatory responses in the infectious process through multiple parameters, including the toll-like receptor (TLR)-4 pathway, which is the main LPS signaling in sepsis. Additionally, previous studies have shown that physical exercise can be both a protector factor and an aggravating factor for some kidney diseases. This study aims at analyzing whether physical exercise before the induction of LPS endotoxemia can protect kidneys from acute kidney injury. Methods:C57BL/6J male mice, 12 weeks old, were distributed into four groups: (1) sedentary (control,N= 7); (2) sedentary + LPS (N= 7); (3) trained (N= 7); and (4) trained + LPS (N= 7). In the training groups, the animals exercised 5x/week in a treadmill, 60 min/day, for 4 weeks (60% of max. velocity). Sepsis was induced in the training group by the application of a single dose of LPS (5 mg/kg i.p.). Sedentary animals received LPS on the same day, and the non-LPS groups received a saline solution instead. All animals were euthanized 24 h after the administration of LPS or saline. Results:The groups receiving LPS presented a significant increase in serum urea (p< 0.0001) and creatinine (p< 0.001) concentration and renal gene expression of inflammatory markers, such as tumor necrosis factor alpha and interleukin-6, as well as TLRs. In addition, LPS promoted a decrease in reduced glutathione. Compared to the sedentary + LPS group, trained + LPS showed overexpression of a gene related to kidney injury (NGAL,p< 0.01) and the protein levels of LPS receptor TLR-4 (p< 0.01). Trained + LPS animals showed an expansion of the tubulointerstitial space in the kidney (p< 0.05) and a decrease in the gene expression of hepatic AOAH (p< 0.01), an enzyme involved in LPS clearance. Conclusion:In contrast to our hypothesis, training was unable to mitigate the renal inflammatory response caused by LPS. On the contrary, it seems to enhance injury by accentuating endotoxin-induced TLR-4 signaling. This effect could be partly due to the modulation of a hepatic enzyme that detoxifies LPS. (AU)

• FAPESP's process: 15/20082-7 - Kallikrein kinin system in physical exercise and metabolism
• Grantee: Ronaldo de Carvalho Araújo
• Support Opportunities: Research Projects - Thematic Grants