Delayed administration of zingerone mitigates the behavioral and histological alteration via repression of oxidative stress and intrinsic programmed cell death in focal transient ischemic rats

作者：Vaibhav Kumar; Shrivastava Pallavi; Tabassum Rizwana; Khan Andleeb; Javed Hayate; Ahmed Md Ejaz; Islam Farah; Safhi Mohammed M; Islam Fakhrul

来源：Pharmacology Biochemistry and Behavior, 2013, 113: 53-62.

DOI：10.1016/j.pbb.2013.10.008

• Apaf-1
• Bax
• Bcl-2
• Behavior
• Caspase
• Ischemia-reperfusion

The neuronal mitochondria succumb to ischemia-reperfusion injury and release huge amount of reactive oxygen species and ultimately lead the neurons to intrinsic pathway of programmed cell death (iPCD). The present study was undertaken to elucidate the ischemia-reperfusion-induced oxidative stress and molecular events in iPCD 24h post ischemia-reperfusion injury and plausible mitigation by zingerone, a potent antioxidant of ginger rhizome. The right middle cerebral artery was occluded for 2 h followed by reperfusion for 22 hours. A maximum infarct volume (43.29%) and mitochondrial injury (56.99%) was observed in middle cerebral artery occlusion (MCAO) group. However, zingerone administration (50 and 100 mg/kg b.wt. orally twice) at 5 h and 12 h from initiation of MCAO showed a significant reduction in infarct volume and mitochondrial injury (p < 0.001). Zingerone, treatment significantly improved behavioral outputs (p < 0.05) and histological architecture (p < 0.001) by reducing lipid peroxidation (p < 0.01), augmenting the reduced glutathione content (p < 0.01) and restoring Na+-K+ ATPase and superoxide dismutase activities (p < 0.01) in MCAO brain. Zingerone successfully reduced the caspase-3 and -9 activities in MCAO group (p < 0.05) and succeeded in lowering the expressions of proapoptotic proteins -Apaf-1 and Bax (p < 0.001). The present study suggests that zingerone is a potent antioxidant that salvaged the ischemic penumbral zone neurons by inhibiting iPCD and oxidative stress.

• 出版日期2013-11-15