Abstract
The goal of this study was to elucidate the mechanisms of protection of Sodium (±)-5-bromo-2-(α-hydroxypentyl) benzoate (trade name: Brozopine, BZP) against cerebral ischemia in vivo and in vitro. To explore the protective effect of BZP on focal cerebral ischemia-reperfusion injury, we evaluated the effects of various doses of BZP on neurobehavioral score, cerebral infarction volume, cerebral swelling in MCAO rats (ischemia for 2 h, reperfusion for 24 h). In addition, the effects of various doses of BZP on OGD/R-induced-PC12 cells injury (hypoglycemic medium containing 30 mmol Na2S2O4 for 2 h, reoxygenation for 24 h) were evaluated. Four in vivo and in vitro groups were evaluated to characterize targets of BZP: Control group, Model group, BZP group (10 mg/kg)/BZP group (30 μmol/L), C8E4 group (10 mg/kg)/C8E4 group (30 μmol/L). An ELISA kit was used to determine the levels of 15-HETE (a 15-LOX-2 metabolite) in vivo and in vitro. Rat nuclear factor κB subunit p65 (NF-κB p65), tumor necrosis factor (TNF-α), interleukin-6 (IL-6), and intercellular adhesion molecule-1 (ICAM-1) were also quantified in vivo and in vitro. The results showed that BZP improved focal cerebral ischemia-reperfusion injury in rats and PC12 cells treated with Na2S2O4 in dose/concentration-dependent manners through inhibition of production of 15-HETE and expression of NF-κB, IL-6, TNF-α, and ICAM-1. In conclusion, BZP exerted protective effects against cerebral ischemia via inhibition of 15-LOX-2 activity.
Highlights
Cerebral ischemia is a leading cause of death and long-term disability (Hayashi et al, 2015; Benjamin et al, 2018; Pandian et al, 2018), and is the most common neurological disease in the world (Roger et al, 2012)
Tetraethylene glycol monooctyl ether (C8E4) was used as a positive control to further characterize the effects of Sodium-5-bromo-2-(a-hydroxypentyl) benzoate (BZP) on focal cerebral ischemiareperfusion injury and PC12 cell hypoxic injury induced by Sodium hyposulfite (Na2S2O4)
BZP treatment improved the survival rate and morphology of hypoxic PC12 cells. These results indicated that BZP exerted protective effects against focal cerebral ischemia-reperfusion injury and PC12 cell hypoxic injury induced by Na2S2O4
Summary
Cerebral ischemia is a leading cause of death and long-term disability (Hayashi et al, 2015; Benjamin et al, 2018; Pandian et al, 2018), and is the most common neurological disease in the world (Roger et al, 2012). Neuroinflammation and oxidative stress are the main pathological mechanisms of cerebral ischemia-reperfusion, and can lead to neurological dysfunction and brain injury (Zhang et al, 2017). Antiinflammatory or antioxidant drugs could be used for treatment of cerebral ischemia-reperfusion injury. Lipoxygenases (LOX) are non-heme iron enzymes that can oxygenate unsaturated fatty acids such as arachidonic acid (AA) to produce bioactive metabolites. The levels of free fatty acids (including AA) increase following cerebral ischemia. Increased free AA could result in production of leukotrienes, hydroxy eicosatetraenoic acids, and other bioactive substances produced by 15-LOX. These molecules contribute to pathophysiological processes such as oxidative stress and inflammation after stroke, and can contribute to apoptosis. Better understanding of the role 15-LOX after stroke could elucidate novel therapeutic strategies for clinical treatment
Sign-in/Register to view highlights & summary Talk to us
Join us for a 30 min session where you can share your feedback and ask us any queries you have
Schedule a callDisclaimer: All third-party content on this website/platform is and will remain the property of their respective owners and is provided on "as is" basis without any warranties, express or implied. Use of third-party content does not indicate any affiliation, sponsorship with or endorsement by them. Any references to third-party content is to identify the corresponding services and shall be considered fair use under The CopyrightLaw.
