Sulforaphane treatment prevents acute exhaustive exercise induced muscle damage in rats.

Acute, exhaustive exercises lead to a burst of reactive oxygen species (ROS) generation that increases the GSSG/GSH ratio in plasma (1), and causes structural damage to muscle cells as evidenced by an increase in plasma activity of cytosolic enzymes such as lactate dehydrogenase (LDH) and creatine kinase. Acute exhaustive exercise can be considered an interesting model of oxidative stress and muscle damage. To prevent and counteract ROS generation and oxidative stress during exercise, many studies have been focused on the use of natural compounds with ROS scavenging properties acting as direct antioxidants, but the overall results are still inconclusive. In this study we have investigated the possibility to counteract exhaustive exercise induced oxidative stress and muscle damage in rats by treating animals with sulforaphane (SF). SF is a naturally occurring isothiocyanate present in the human diet and originating from the ingestion of Cruciferous vegetables. SF is known to induce phase 2 enzymes with antioxidant properties in many tissues, but no data are still available on skeletal muscle tissues. In our study male Wistar rats (age 4 months, weight 230±20g) were treated every 24 hours with SF (25 mg/kg bw i.p.) for three days before undergoing an acute exhaustive exercise protocol. The exercise protocol consisted in running on a treadmill at 24 m/min and 7% gradient. Exhaustion was defined as the point at which the animals failed to get off the shock grid and thus had to be manually repositioned to the front of the treadmill on three consecutive occasions. Animals were sacrificed and LDH activity was determined on plasma samples. The activities of phase 2 enzymes such as NAD(P)H:quinone oxidoreductase (NQO1), glutathione-S-transferase (GST), glutathione reductase (GR), glutathione peroxidase (GPx), thioredoxin reductase (TR) and superoxide dismutase (SOD) and catalase (CAT) were evaluated in homogenates from freshly excised vastus lateralis skeletal muscle. SF treatment significantly induced the activity of NQO1, GST and GR in skeletal muscle tissues, with no effect on GPx, TR, SOD and CAT activities. Upregulation of phase 2 enzymes correlated with a decrease in oxidative damage in muscles, as evidenced by a significant decrease in LDH release in plasma after SF treatment. Our data, for the first time, demonstrate that SF could play a critical role in the modulation of muscle redox environment leading to the prevention of exhaustive exercise induced muscle damage. These results suggest that SF could become an interesting natural compound in the development of a dietary intervention that promotes oxidant scavenging through phase 2 protein induction and in the development of new dietary supplements for physical active people. Research supported by Fondazione del Monte di BO e RA. 1. Sastre J et al. Am J Physiol. 1992;263:R992-995.