The Effects of Sulforaphane Treatment in an in vivo Model of PAD

Peripheral artery disease (PAD) is a disorder caused by atherosclerosis in the peripheral arteries, especially the legs, which affects mobility and quality of life as the disease progresses. The blockage in the arteries leads to cycles of ischemia and reperfusion, damaging the surrounding skeletal muscle tissue. This damage primarily results from mitochondrial dysfunction caused by the cyclic changes in oxygen concentration. As most treatments for severe PAD require invasive surgery, in this study we sought to determine if the phytochemical sulforaphane could be used as a noninvasive method to address mitochondrial dysfunction in an in vivo murine model of PAD. Sulforaphane was administered in animal drinking water via two different treatment protocols. One group received sulforaphane supplementation for 7 days pre and post hind limb ligation, whereas the other treatment group only received sulforaphane for the 7 days following surgical ligation. Control mice received normal drinking water. The sulforaphane-treated groups experienced better post-surgical recovery as measured by critical limb use and percent body weight change. The soleus muscle was extracted from all animals 7 days following hindlimb ligation, and muscle mitochondrial function (oxygen consumption and reactive oxygen species (ROS) production) was assessed using fluoro respirometry. Although muscle from sulforaphane-treated mice showed an increase in oxygen consumption when compared to control animals, ROS production was also increased. The increase in ROS production was unexpected considering previous research suggests sulforaphane acts to reduce ROS production. However, there was much inter-individual variability noted in the data of the current study. Although there are some promising results for sulforaphane as a potential treatment for PAD, there is a clear need for further study. In the future, it will be important to increase the number of mice per experimental group to decrease standard deviation as well as refine our data normalization protocols associated with the experiments.