Rhein protects against cerebral ischemic-/reperfusion-induced oxidative stress and apoptosis in rats

Abstract

The present study aimed to investigate the protective effects of rhein on cerebral ischemic/reperfusion (I/R) injury in rats. The present study focused on the effect of rhein on oxidative stress and apoptotic factors, which are considered to serve an important role in the onset of I/R injury. Sprague-D awley rats were subjected to middle cerebral artery occlusion. Neurological functional scores (NFSs) were evaluated according to the Zea Longa's score criteria and the area of brain infarct was determined by triphenyltetrazolium chloride staining. The morphology of the nerve cells in the cortex was observed following hematoxylin and eosin staining. In addition, levels of oxidative stress were assessed by measuring the levels of superoxide dismutase (SOD), glutathione-peroxidase (GSH-Px), catalase (CAT) and malondialdehyde (MDA). Levels of B-cell lymphoma-2 (Bcl-2), apoptosis regulator Bax (BAX), caspase-9, caspase-3 and cleaved caspase-3 expression were analyzed using western blot analysis. Levels of caspase-9 and caspase-3 mRNA expression were obtained using reverse transcription-quantitative polymerase chain reaction. The results revealed that treatment with 50 or 100 mg/kg rhein significantly improved the NFS and markedly attenuated the area of infarction. Rhein also significantly reduced the content of MDA and significantly increased SOD, GSH-Px and CAT activity. Western blot analysis indicated that rhein significantly decreased the expression of BAX and enhanced the expression of Bcl-2. Compared with the I/R group, levels of caspase-9, caspase-3 and cleaved caspase-3 protein expression were significantly decreased in the rhein treatment groups. Additionally, rhein treatment significantly reduced levels of caspase-9 and caspase-3 mRNA expression. These results suggest that rhein exhibits protective effects during cerebral I/R injury and its underlying mechanism of action may involve the inhibition of oxidative stress and apoptosis.