Effects of astaxanthin on oxidative stress and inflammatory reaction in rats with traumatic brain injury based on Nrf2/HO-1 signaling pathway
- VernacularTitle:基于Nrf2/HO-1信号通路探讨虾青素对创伤性脑损伤模型大鼠氧化应激和炎症反应的影响
- Author:
Yuguang YI
1
;
Changping LIU
1
;
Jiajia HE
1
Author Information
1. Dept. of Neurosurgery,Pingxiang Second People’s Hospital,Jiangxi Pingxiang 337000,China
- Publication Type:Journal Article
- Keywords:
astaxanthin;
traumatic brain injury;
oxidative stress;
inflammatory reaction;
Nrf2/HO-1 signaling pathway
- From:
China Pharmacy
2023;34(20):2490-2496
- CountryChina
- Language:Chinese
-
Abstract:
OBJECTIVE To investigate the effects of astaxanthin on oxidative stress and inflammatory reaction in rats with traumatic brain injury (TBI). METHODS Male SD rats were randomly divided into sham operation group, model group, astaxanthin low-dose group (20 mg/kg), astaxanthin high-dose group (40 mg/kg), astaxanthin+ML385 group [astaxanthin 40 mg/kg+ nuclear factor-erythroid 2-related factor 2 (Nrf2) inhibitor ML385 30 mg/kg], with 14 rats in each group. Except for the sham operation group, TBI model was induced by the modified Feeney free-fall impact method in other groups. The rats in each drug group were given the corresponding drug intragastrically or intraperitoneally, and the rats in the sham operation group and model group were intragastrically given a constant volume of normal saline. The neurological function of rats in each group was scored on the 1st, 3rd and 7th day after drug intervention; on the 7th day of drug intervention, the changes of cerebral histomorphology and inflammatory infiltration score were observed in each group, and the ultrastructure of nerve cells in brain tissue was also observed. The contents of oxidative stress indexes [superoxide dismutase (SOD), catalase (CAT), glutathione peroxidase (GSH-Px), malondialdehyde (MDA), nitric oxide (NO)] and inflammatory reaction indexes [tumor necrosis factor-α, interleukin-1β (IL-1β), IL-6, inducible nitric oxide synthase] as well as protein and mRNA expressions of Nrf2, heme oxygenase-1 (HO-1) and NAD(P)H: quinone oxidoreductase 1 (NQO1) were detected in cerebral tissue. RESULTS Compared with the sham operation group, the brain edema of rats in the model group was obvious, accompanied by a large number of inflammatory cells infiltrated, the shape of organelles was damaged and their number was reduced, and the ultrastructure of nerve cells was seriously damaged. The neurological function score, the contents of SOD, CAT, GSH-Px and NO and the relative expression levels of Nrf2, HO-1 and NQO1 protein and mRNA in brain tissue were significantly decreased, while the inflammatory infiltration scores, the contents of MDA and inflammatory reaction indexes were significantly increased (P<0.05). Compared with the model group, low-dose and high-dose astaxanthin could significantly improve the pathological status of brain tissue and nerve cells and neurological function scores (except for the first day of drug intervention in the astaxanthin low-dose group), increase the contents of SOD, CAT, GSH-Px and NO and the relative expression levels of Nrf2, HO-1, NQO1 protein and mRNA in brain tissue in a dose-dependent manner, and reduce inflammatory infiltration scores, the contents of MDA and inflammatory reaction indexes (P<0.05). ML385 could significantly inhibit the above effects of astaxanthin (P<0.05). CONCLUSIONS Astaxanthin may reduce the oxidative stress of TBI model rats, alleviate the neurological damage and reduce the level of inflammation reaction by activating the Nrf2/HO-1 signaling pathway.