Effects of apple polyphenols on oxidative stress and cerebral vasospasm after subarachnoid hemorrhage in a rabbit double hemorrhage model

Abstract

Subarachnoid hemorrhage (SAH) is almost always caused by ruptured cerebral aneurysms, and the most serious complication after SAH is cerebral vasospasm. Oxidative stress due to free radicals released from subarachnoid hemorrhage clots causes cerebral vasospasm, as proven by animal experiments. Apple polyphenols have already been demonstrated to strongly suppress oxidized low-density lipoprotein (ox-LDL) and lectin-like oxidized LDL receptor-1 (LOX-1) derived from reactive oxygen species (ROS), and to improve cerebral vasospasm. However, it is unclear how apple polyphenol acts downstream of ROS. The purpose of this study is to reveal a more detailed mechanism of functioning for apple polyphenols in suppressing oxidative stress and cerebral vasospasm. Using the double-hemorrhage rabbit subarachnoid hemorrhage (SAH) model, we investigated the effect of apple polyphenols by measuring the basilar artery diameter, endothelial NO synthase (eNOS) expression, diacron reactive oxygen metabolites (d-ROM), biological antioxidant potential (BAP), and malondialdehyde (MDA). The mean diameter of the basilar artery in the apple polyphenol treatment group was significantly larger than in the SAH group (p < 0.01). The expression of endothelial nitric oxide synthase (eNOS), evaluated by immunohisto-chemistry in the apple polyphenol treatment group, was higher than in the SAH group (p < 0.05). The BAP test in the apple polyphenol treatment group showed a significant difference, while there was no significant difference in the values of d-ROM and MDA. The results of the present study revealed that apple polyphenol significantly improved cerebral vasospasm and eNOS. In spite of a significant increase in antioxidant power expressed by increased BAP, oxidative stress measured by the d-ROM value was not significantly suppressed. Either the number of experimental animals was not sufficient to reach statistical significance, or the eNOS increase due to apple polyphenols and suppression of vasospasm are attributable to pathways other than lipid oxidation detected by MDA.