Therapeutic Potential of GYY4137 in Reducing Oxidative

The pathophysiology of decompression sickness (DCS) is not fully understood. Apart from 13 bubble formation, endothelial dysfunction and reactive oxygen species (ROS) production, 14 participate in DCS. We aimed to evaluate the redox profile (redox potential, adenosine 15 deaminase activity (ADA), and xanthine oxidase activity (XO)) and the effects of GYY4137, an 16 H2S donor with antiradical properties, on the mortality of mice exposed to experimental DCS. 17 Sixty Mice were injected intraperitoneally with either GYY4137 or vehicle, then subjected to 18 high pressure in a hyperbaric chamber, followed by a quick decompression. GYY4137 increased 19 survival with a median lethal dose (LD50) of 120 m compared with those injected with vehicle (< 20 100 m; p = 0.038) but did not affect ADA or XO activities. The redox potential (RP: mV) was 21 lower in the GYY4137 group (116[78-189]) than that in the vehicle group: 150[88-226],p = 0.04. 22 Experimental decompression sickness itself is associated with an increase in redox potential. We 23 concluded that GYY4137 protects mice while reducing potential redox and ROS production. Our 24 results seem to indicate that the reduction of the redox potential induced by the administration 25 of thiol donor could reduce morbidity and mortality during DCS.