Neutrophil Depletion Attenuates Acute Renal Injury After Exhaustive Exercise in Mice

Prolonged intense exercise induces acute renal injury; however, the precise mechanism remains unclear. We investigated the effects of neutrophil depletion in male C57BL/6J mice. Male C57BL/6J mice were divided into four groups: sedentary with control antibody; sedentary with antineutrophil antibody; exhaustive exercise with control antibody; and exhaustive exercise with antineutrophil antibody. Antineutrophil (1A8) or control antibody was administered i.p. to the mice before they ran on a treadmill. Plasma levels of creatinine and blood urea nitrogen (BUN) were measured. Renal histology was assessed 24 h after exhaustive exercise, and the concentration of kidney injury molecule (KIM)-1 was measured using an enzyme-linked immunosorbent assay. The expression levels of inflammatory cytokines were measured using qRT-PCR. Furthermore, NADPH oxidase activity and the hydrogen peroxide concentration in the kidney were measured. Immediately after exhaustive exercise, plasma BUN was significantly increased, but creatinine was not. The increase in BUN after exercise was suppressed by 1A8 treatment. The pathological changes manifested as congested and swollen glomeruli and nuclear infiltration after exhaustive exercise. These changes were suppressed by treatment with the 1A8 antibodies. The KIM-1 concentration increased after exhaustive exercise but was reduced by the 1A8 antibodies. Treatment with the 1A8 antibody also decreased exhaustive exercise-induced inflammation and reactive oxygen species levels in the kidney. These results suggest that neutrophils contribute to exercise-induced acute renal injury by regulating inflammation and oxidative stress.