Protective Effects of Sulforaphane on Exercise-Induced Organ Damage via Inducing Antioxidant Defense Responses

Abstract

Regular exercise is beneficial to maintain a healthy lifestyle, but the beneficial effects are lost in the case of acute exhaustive exercise; this causes significant inflammation, oxidative stress along with organ damage. Recently, sulforaphane (SFN), an indirect antioxidant, has drawn special attention for its potential protective effect against inflammation and oxidative stress. However, no studies have been performed regarding acute exhaustive exercise-induced organ damage in association with SFN administration. Therefore, the aim of this study was to investigate the effects of SFN on acute exhaustive exercise-induced organ damage and the mechanisms involved. To perform the study, we divided mice into four groups: Control, SFN, exercise, and SFN plus exercise. The SFN group was administered orally (50 mg/kg body wt) 2 h before the running test. We measured plasma levels of alanine aminotransferase (ALT), aspartate aminotransferase (AST), and lactate dehydrogenase (LDH), and acute exhaustive exercise significantly increased these biomarkers. In addition, the mRNA expression of pro-inflammatory cytokines, IL-6, IL-1β, and TNF-α, were significantly increased in the liver of exercise group. However, the SFN plus exercise group showed a significant reduction in the expression of cytokines and blood biomarkers of tissue damage or cell death. Furthermore, we measured mRNA expression of Nrf2, heme oxygenase (HO)-1, and antioxidant defense enzymes expression, i.e., superoxide dismutase (SOD1), catalase (CAT), and glutathione peroxidase (GPx1) in the liver. The expression of all these biomarkers was significantly upregulated in the SFN plus exercise group. Collectively, SFN may protect the liver from exhaustive exercise-induced inflammation via inducing antioxidant defense response through the activation of Nrf2/HO-1 signal transduction pathway.

Keywords: Nrf2; antioxidant; antioxidant enzymes; cytokines; exercise; inflammation; oxidative stress; sulforaphane.

Figure 1

Experimental design and exhaustive exercise protocol.

Figure 2

Plasma enzyme level comparison between the sedentary (Sed) and exercise (Ex) groups, with (sulforaphane; SFN) or without (control; Con) supplement. Figure 2 (A–C) represent aspartate aminotransferase (AST); alanine aminotransferase (ALT) and lactate dehydrogenase (LDH) levels in plasma. ### p < 0.001, ## p < 0.01, # p < 0.05 as compared to the sedentary control. *** p < 0.001, * p < 0.05. Interaction of SFN and Ex written as “Interaction”. Data are presented as mean ± SE.

Figure 3

Interleukin-6 (IL-6) mRNA (A), Tumor necrosis factor-α (TNF-α) mRNA (B), and Interleukin-1β (IL-1β) mRNA (C) expression in the comparison between the sedentary (Sed) and exercise (Ex) groups, with (sulforaphane; SFN) or without (control; Con) supplement. ### p < 0.001, ## p < 0.01, # p < 0.05 as compared to the sedentary control. ** p < 0.01, * p < 0.05. Interaction of SFN and Ex written as “Interaction”. Data are presented as mean ± SE.

Figure 4

Superoxide dismutase 1 (SOD1) mRNA (A), Catalase (CAT) mRNA (B), and Glutathione peroxidase 1 (GPx1) mRNA (C) expression in the liver in the comparison between the sedentary (Sed) and exercise (Ex) groups, with (sulforaphane; SFN) or without (control; Con) supplement. ### p < 0.001, # p < 0.05 as compared to the sedentary control. ** p < 0.01, * p < 0.05. Interaction of SFN and Ex written as “Interaction”. Data are presented as mean ± SE.

Figure 5

Nuclear factor E2 factor-related factor (Nrf2) mRNA (A) and Heme oxygenase 1 (HO-1) mRNA (B) expression in the liver in the comparison between the sedentary (Sed) and exercise (Ex) groups, with (sulforaphane; SFN) or without (control; Con) supplement. ### p < 0.001 as compared to the sedentary control. *** p < 0.001, * p < 0.05. Interaction of SFN and Ex written as “Interaction”. Data are presented as mean ± SE.