Melatonin activates the Nrf2-ARE pathway when it protects against early brain injury in a subarachnoid hemorrhage model
| Autor: | Chengjie Meng, Xue-Bo Sun, Gang Chen, Guo-Qing Zhu, Hui-Xiang Liu, Xu-Ming Shen, Chao Ma, Zhong Wang, Zhang Shu, Wei-Chun He, Jian Zhang, Lei Huo |
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| Rok vydání: | 2012 |
| Předmět: |
Antioxidant
Subarachnoid hemorrhage business.industry medicine.medical_treatment Glutathione Pharmacology medicine.disease medicine.disease_cause nervous system diseases Melatonin chemistry.chemical_compound Endocrinology chemistry Apoptosis Anesthesia medicine cardiovascular diseases NAD+ kinase business Heme Oxidative stress medicine.drug |
| Zdroj: | Journal of Pineal Research. 53:129-137 |
| ISSN: | 0742-3098 |
| DOI: | 10.1111/j.1600-079x.2012.00978.x |
| Popis: | Melatonin has beneficial effects against early brain injury (EBI) by modulating cerebral oxidative stress after experimental subarachnoid hemorrhage (SAH); however, few investigations relate to the precise underlying molecular mechanisms. To date, the relation between melatonin and nuclear factor erythroid 2-related factor 2 and antioxidant responsive element (Nrf2-ARE) pathway has not been studied in SAH models. This study was undertaken to evaluate the influence of melatonin on Nrf2-ARE pathway in rats after SAH. Adult male SD rats were divided into four groups: (i) control group (n = 18); (ii) SAH group (n = 18); (iii) SAH + vehicle group (n = 18); and (iv) SAH + melatonin group (n = 18). The rat SAH model was induced by injection of 0.3 mL fresh arterial, nonheparinized blood into the prechiasmatic cistern in 20 s. In SAH + melatonin group, melatonin was administered i.p. at 150 mg/kg at 2 and 24 hr after the induction of SAH. Brain samples were extracted at 48 hr after SAH. Treatment with melatonin markedly increased the expressions of Nrf2-ARE pathway-related agents, such as Nrf2, heme oxygenase-1, NAD(P)H:quinone oxidoreductase 1, and glutathione S-transferase α-1. Administration of melatonin following SAH significantly ameliorated EBI, including brain edema, blood–brain barrier (BBB) impairment, cortical apoptosis, and neurological deficits. In conclusion, post-SAH melatonin administration may attenuate EBI in this SAH model, possibly through activating Nrf2-ARE pathway and modulating cerebral oxidative stress by inducing antioxidant and detoxifying enzymes. |
| Databáze: | OpenAIRE |
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