Astaxanthin ameliorates oxidative stress and neuronal apoptosis after traumatic brain injury in mice. - GreenMedInfo Summary
Astaxanthin ameliorates oxidative stress and neuronal apoptosis via SIRT1/Nrf2/Prx2/ASK1/P38 after traumatic brain injury in mice.
Br J Pharmacol. 2020 Dec 16. Epub 2020 Dec 16. PMID: 33326114
Xiang-Sheng Zhang
BACKGROUND AND PURPOSE: Oxidative stress and neuronal apoptosis play key roles in the development of traumatic brain injury (TBI). Here we investigated the protective effects of astaxanthin (ATX) against TBI and tried to discover its underlying mechanisms of action.
EXPERIMENTAL APPROACH: A weight-drop model of TBI in vivo and hydrogen peroxide exposure in vitro model was established respectively. Brain edema, behavior tests, western blot, biochemical analysis, lesion volume, histopathological study, and cell viability were performed.
KEY RESULTS: ATX significantly reduced oxidative insults on day 1, 3, and 7 after TBI. Neuronal apoptosis was also ameliorated on day 3 after ATX administration. Additionally, ATX improved neurological functions up to 3 weeks after TBI. Mechanically, ATX treatment dramatically enhanced the expression of peroxiredoxin 2 (Prx2), nuclear factor-erythroid 2-related factor 2 (Nrf2), and sirtuin 1 (SIRT1), while it downregulated the phosphorylation of apoptosis signal-regulating kinase 1 (ASK1) and p38. Inhibition of Prx2 by small interfering ribonucleic acid injection reversed the beneficial effects of ATX against TBI. Additionally, Nrf2 knockout abated the neuroprotective effects of ATX in TBI. In contrast, over-expression of Prx2 in Nrf2 knockout mice attenuated the secondary brain injury after TBI. Moreover, inhibiting SIRT1 by EX527 dramatically abrogated the neuroprotective effects of ATX, and suppressed SIRT1/Nrf2/Prx2/ASK1/p38 pathway both in vivo and in vitro.
CONCLUSION AND IMPLICATIONS: ATX improved the neurologic functions and protected the brain from injury after TBI, primarily by reducing oxidative stress and neuronal death via SIRT1/Nrf2/Prx2/ASK1/p38 signaling pathway. ATX might be a new candidate to ameliorate TBI.