Photoisomerization Neutralizes Vasoconstrictive Activity of a Heme Degradation Product

ACS Omega. 2020 Aug 20;5(34):21401-21411. doi: 10.1021/acsomega.0c01698. eCollection 2020 Sep 1.


Delayed cerebral ischemia (DCI) caused by cerebral vasospasm is the leading determinant of poor outcome and mortality in subarachnoid hemorrhage (SAH) patients, but current treatment options lack effective prevention and therapy. Two substance families of heme degradation products (HDPs), bilirubin oxidation end products (BOXes) and propentdyopents (PDPs), are elicitors of pathologic cerebral hypoperfusion after SAH. Z-configured HDPs can be photoconverted into the corresponding E-isomers. We hypothesize that photoconversion is a detoxification mechanism to prevent and treat DCI. We irradiated purified Z-BOXes and Z-PDPs with UV/Vis light and documented the Z-E photoconversion. E-BOX A slowly reisomerizes to the thermodynamically favored Z-configuration in protein-containing media. In contrast to vasoconstrictive Z-BOX A, E-BOX A does not cause vasoconstriction in cerebral arterioles in vitro and in vivo in wild-type mice. Our results enable a critical assessment of light-induced intrathecal photoconversion and suggest the use of phototherapy to prevent and cure HDP-mediated cerebral vasospasms.