Differential time responses in inflammatory and oxidative stress markers after a marathon: An observational study

ABSTRACT

Acute and adaptive changes in systemic markers of oxidatively generated nucleic acid modifications (i.e., 8-oxo-7,8-dihydro-2ʹ-deoxyguanosine (8-oxodG) and 8-oxo-7,8-dihydroguanosine (8-oxoGuo)) as well as inflammatory cytokines (i.e., C-reactive protein, interleukin-6, interleukin-10, and tumour necrosis factor alpha), a liver hormone (i.e., fibroblast growth factor 21 (FGF21)), and bone metabolism markers (sclerostin, osteocalcin, C-terminal telopeptide, and N-terminal propeptide of type 1 procollagen) were investigated following a marathon in 20 study participants. Immediate changes were observed in inflammatory cytokines, FGF21, and bone metabolism markers following the marathon. In contrast, no immediate changes in urinary excretion of 8-oxodG and 8-oxoGuo were evident. Four days after the marathon, decreased urinary excretion of 8-oxodG (-2.9 (95% CI -4.8;-1.1) nmol/24 h, P < 0.01) and 8-oxoGuo (-5.8 (95% CI -10.3;-1.3) nmol/24 h, P = 0.02) was observed. The excretion rate of 8-oxodG remained decreased 7 days after the marathon compared to baseline (-2.3 (95%CI -4.3;-0.4) nmol/24 h, P = 0.02), whereas the excretion rate of 8-oxoGuo was normalized. In conclusion marathon participation immediately induced a considerable inflammatory response, but did not increase excretion rates of oxidatively generated nucleic acid modifications. In fact, a delayed decrease in oxidatively generated nucleic acid modifications was observed suggesting adaptive antioxidative effects following exercise.

Abbreviations

8-oxodG: 8-oxo-7,8-dihydro-2ʹ-deoxyguanosine; 8-oxoGuo: 8-oxo-7,8-dihydroguanosine; CI: confidence interval; CTX: C-terminal telopeptide of type 1 collagen; DXA: dual-energy X-ray absorptiometry; ELISA: enzyme-linked immunosorbent assay; FGF21: Fibroblast growth factor 21; h: hour; hsCRP: high sensitivity C-reactive protein; IL: interleukin; IQR: interquartile range; MS: mass spectrometry: P1NP: N-terminal propeptide of type 1 procollagen; TNFα: tumour necrosis factor alpha; UPLC: ultra-performance liquid chromatography

Graphical abstract

KEYWORDS:

• Bone metabolism
• exercise
• fibroblast growth factor 21
• inflammation
• oxidative stress

Acknowledgments

We thank senior laboratorian technician Lis Kjær Hansen, laboratory technicians Stine W. Frederiksen and Agnethe Mehlsen for their tremendous help during this study. We thank chemist Trine Henriksen and laboratory technician Katja R. Christensen for conducting the urine analysis of 8-oxodG, 8-oxoGuo, and creatinine. We are grateful to Mathias Ried-Larsen and Cecilie Fau Brinkløv for helping with the accelerometer measurement although the data were not used in the current paper. We thank Sparta Atletik & Motion for providing a location and facility at the finish area of Copenhagen Marathon 2018, ‘A.P. Møller Fonden - Fonden for Lægevidenskabens Fremme’ for providing funding for this study and Centre of Active Research for letting us use their equipment at study visit 5, and www.smart.servier.com for providing an image for the graphical abstract. ML has received a research grant from the Danish Diabetes Academy supported by the Novo Nordisk Foundation. At last, but foremost, we thank the participants for making this study possible.

Disclosure statement

All authors declare no conflict of interest in relation to this study.

Supplementary material

Supplementary data for this article can be accessed here

Additional information

Funding

This work was supported by the A.P. Møller Fonden - Fonden til Lægevidenskabens Fremme (17-L-0305); Danish Diabetes Academy supported by Novo Nordisk Foundation.