Sulforaphane Inhibits Exhaustive Exercise-Induced Liver Injury and Transcriptome-Based Mechanism Analysis

Abstract

Exhaustive exercise (EE) induces liver injury and has recently gained much attention. Sulforaphane (SFN) can protect the liver from inflammation and oxidative stress. However, the effects of SFN on EE-induced liver injury and its underlying mechanisms are still unclear. C57BL/6J mice swimming to exhaustion for seven days were used to simulate the liver injury caused by EE. Different doses of SFN (10, 30, 90 mg/kg body weight) were gavage-fed one week before and during the exercise. SFN intervention significantly reduced the EE-induced lactate dehydrogenase (LDH), creatine kinase (CK), alanine aminotransferase (ALT), and aspartate aminotransferase (AST) in the serum, as well as attenuating liver tissue morphological abnormality, oxidative stress injury, and inflammation. Liver transcriptomic analysis showed that the differentially expressed genes altered by SFN intervention in the exercise model were mainly enriched in glucose and lipid metabolism pathways. The most altered gene by SFN intervention screened by RNA-seq and validated by qRT-PCR is Ppp1r3g, a gene involved in regulating hepatic glycogenesis, which may play a vital role in the protective effects of SFN in EE-induced liver damage. SFN can protect the liver from EE-induced damage, and glucose and lipid metabolism may be involved in the mechanism of the protective effects.

The Immunomodulatory Effects of Sulforaphane in Exercise-Induced Inflammation and Oxidative Stress: A Prospective Nutraceutical

“…Further, SFN contributed effectively in a muscular dystrophy x-linked (mdx) knock-out model; oral administration of SFN (2 mg/kg/day) for eight weeks, followed by an acute exercise protocol, protected dystrophic muscles from oxidative damage in mdx mice and improved the muscle function, ROS level, and inflammation and reduced immune cell infiltration [40]. Yang et al conducted a study and reported that SFN protected the liver from exhaustive exerciseinduced excessive ROS production [41]. We also reported that a single dose of SFN ad-ministration may protect the liver from exhaustive exercise-induced oxidative stress and inflammation [35].…”

“…At the same time, SFN increases the transcriptional activation of these essential genes' expression by restoring the Keap1/Nrf2/ARE pathway [38]. Besides improving endurance capacity, SFN preintervention protects from exhaustive exercise-induced liver damage [41]. Yang et al conducted an animal study with a mild and high dose of SFN and executed exhaustive exercise for seven consecutive days along with SFN treatment and reported that an SFN intervention improved the adequacy of antioxidative stress and reduced inflammation in the liver and therefore diminished liver damage and ameliorated exercise endurance [41].…”