Astaxanthin activates nuclear factor erythroid-related factor 2 and the antioxidant responsive element (Nrf2-ARE) pathway in the brain after subarachnoid hemorrhage in rats and attenuates early brain injury.

Qi Wu,Xiang-Sheng Zhang,Han-Dong Wang,Meng-Liang Zhou,Wei Li,Xin Zhang,Xiao-Liang Wang,Qing Yu

doi:10.3390/md12126125

Abstract

Astaxanthin (ATX) has been proven to ameliorate early brain injury (EBI) after experimental subarachnoid hemorrhage (SAH) by modulating cerebral oxidative stress. This study was performed to assess the effect of ATX on the Nrf2-ARE pathway and to explore the underlying molecular mechanisms of antioxidant properties of ATX in EBI after SAH. A total of 96 male SD rats were randomly divided into four groups. Autologous blood was injected into the prechiasmatic cistern of the rat to induce an experimental SAH model. Rats in each group were sacrificed at 24 h after SAH. Expressions of Nrf2 and heme oxygenase-1 (HO-1) were measured by Western blot and immunohistochemistry analysis. The mRNA levels of HO-1, NAD (P) H: quinone oxidoreductase 1 (NQO-1), and glutathione S-transferase-α1 (GST-α1) were determined by real-time polymerase chain reaction (PCR). It was observed that administration of ATX post-SAH could up-regulate the cortical expression of these agents, mediated in the Nrf2-ARE pathway at both pretranscriptional and posttranscriptional levels. Meanwhile, oxidative damage was reduced. Furthermore, ATX treatment significantly attenuated brain edema, blood–brain barrier (BBB) disruption, cellular apoptosis, and neurological dysfunction in SAH models. This study demonstrated that ATX treatment alleviated EBI in SAH model, possibly through activating the Nrf2-ARE pathway by inducing antioxidant and detoxifying enzymes.

Highlights

Astaxanthin (ATX) is a carotenoid widely found in algae and aquatic animals, which has powerful antioxidant activity [1]
The Nrf2-ARE pathway has been proven to play a beneficial role in early brain injury (EBI) after subarachnoid hemorrhage (SAH), possibly through inducing antioxidant and detoxifying enzymes to reduce cerebral oxidative stress [10]
An independent investigator blinded to the experimental groups and carried out a battery of tests looking at appetite, activity, and neurological deficits [12] before the rats were sacrificed

Summary

Introduction

Astaxanthin (ATX) is a carotenoid widely found in algae and aquatic animals, which has powerful antioxidant activity [1]. Previous studies have revealed that ATX, with its antioxidative property, is beneficial as a therapeutic agent for various diseases both in vivo and in vitro without any side effects or toxicity [2,3,4]. Our earlier research has demonstrated that ATX administration after subarachnoid hemorrhage (SAH) can up-regulate the cortical endogenous antioxidant agents and prevent oxidative damage in experimental SAH models, alleviating early brain injury (EBI) [5], which is considered the most common cause of disability and death in SAH patients [6]. The Nrf2-ARE pathway has been proven to play a beneficial role in EBI after SAH, possibly through inducing antioxidant and detoxifying enzymes to reduce cerebral oxidative stress [10]

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