Astaxanthin alleviates spinal cord ischemia-reperfusion injury via activation of PI3K/Akt/GSK-3β pathway in rats
Abstract Background Ischemia-reperfusion injury of the spinal cord (SCII) often leads to unalterable neurological deficits, which may be associated with apoptosis induced by oxidative stress and inflammation. Astaxanthin (AST) is a strong antioxidant and anti-inflammatory agent with multitarget neur...
| Main Authors: | , , , , , , , |
|---|---|
| Format: | Article |
| Language: | English |
| Published: |
BMC
2020-07-01
|
| Series: | Journal of Orthopaedic Surgery and Research |
| Subjects: | |
| Online Access: | http://link.springer.com/article/10.1186/s13018-020-01790-8 |
| _version_ | 1828284400493658112 |
|---|---|
| author | Jian Fu Haibin Sun Haofei Wei Mingjie Dong Yongzhe Zhang Wei Xu Yanwei Fang Jianhui Zhao |
| author_facet | Jian Fu Haibin Sun Haofei Wei Mingjie Dong Yongzhe Zhang Wei Xu Yanwei Fang Jianhui Zhao |
| author_sort | Jian Fu |
| collection | DOAJ |
| description | Abstract Background Ischemia-reperfusion injury of the spinal cord (SCII) often leads to unalterable neurological deficits, which may be associated with apoptosis induced by oxidative stress and inflammation. Astaxanthin (AST) is a strong antioxidant and anti-inflammatory agent with multitarget neuroprotective effects. This study aimed to investigate the potential therapeutic effects of AST for SCII and the molecular mechanism. Methods Rat models of SCII with abdominal aortic occlusion for 40 min were carried out to investigate the effects of AST on the recovery of SCII. Tarlov’s scores were used to assess the neuronal function; HE and TUNEL staining were used to observe the pathological morphology of lesions. Neuron oxidative stress and inflammation were measured using commercial detection kits. Flow cytometry was conducted to assess the mitochondrial swelling degree. Besides, Western blot assay was used to detect the expression of PI3K/Akt/GSK-3β pathway-related proteins, as well as NOX2 and NLRP3 proteins. Results The results demonstrated that AST pretreatment promoted the hind limb motor function recovery and alleviated the pathological damage induced by SCII. Moreover, AST significantly enhanced the antioxidative stress response and attenuated mitochondrial swelling. However, AST pretreatment hardly inhibited the levels of proinflammatory cytokines after SCII. Most importantly, AST activated p-Akt and p-GSK-3β expression levels. Meanwhile, cotreatment with LY294002 (a PI3K inhibitor) was found to abolish the above protective effects observed with the AST pretreatment. Conclusion Overall, these results suggest that AST pretreatment not only mitigates pathological tissue damage but also effectively improves neural functional recovery following SCII, primarily by alleviating oxidative stress but not inhibiting inflammation. A possible underlying molecular mechanism of AST may be mainly attributed to the activation of PI3K/Akt/GSK-3β pathway. |
| first_indexed | 2024-04-13T09:01:12Z |
| format | Article |
| id | doaj.art-7de18f9c8c964252b0eb7eb94ecbb1a3 |
| institution | Directory Open Access Journal |
| issn | 1749-799X |
| language | English |
| last_indexed | 2024-04-13T09:01:12Z |
| publishDate | 2020-07-01 |
| publisher | BMC |
| record_format | Article |
| series | Journal of Orthopaedic Surgery and Research |
| spelling | doaj.art-7de18f9c8c964252b0eb7eb94ecbb1a32022-12-22T02:53:09ZengBMCJournal of Orthopaedic Surgery and Research1749-799X2020-07-0115111110.1186/s13018-020-01790-8Astaxanthin alleviates spinal cord ischemia-reperfusion injury via activation of PI3K/Akt/GSK-3β pathway in ratsJian Fu0Haibin Sun1Haofei Wei2Mingjie Dong3Yongzhe Zhang4Wei Xu5Yanwei Fang6Jianhui Zhao7Department of Emergency Surgery, The Second Hospital of Hebei Medical UniversityDepartment of Emergency Surgery, The Second Hospital of Hebei Medical UniversityDepartment of Emergency Surgery, The Second Hospital of Hebei Medical UniversityDepartment of Emergency Surgery, The Second Hospital of Hebei Medical UniversityDepartment of Emergency Surgery, The Second Hospital of Hebei Medical UniversityDepartment of Emergency Surgery, The Second Hospital of Hebei Medical UniversityDepartment of Emergency Surgery, The Second Hospital of Hebei Medical UniversityDepartment of Emergency Surgery, The Second Hospital of Hebei Medical UniversityAbstract Background Ischemia-reperfusion injury of the spinal cord (SCII) often leads to unalterable neurological deficits, which may be associated with apoptosis induced by oxidative stress and inflammation. Astaxanthin (AST) is a strong antioxidant and anti-inflammatory agent with multitarget neuroprotective effects. This study aimed to investigate the potential therapeutic effects of AST for SCII and the molecular mechanism. Methods Rat models of SCII with abdominal aortic occlusion for 40 min were carried out to investigate the effects of AST on the recovery of SCII. Tarlov’s scores were used to assess the neuronal function; HE and TUNEL staining were used to observe the pathological morphology of lesions. Neuron oxidative stress and inflammation were measured using commercial detection kits. Flow cytometry was conducted to assess the mitochondrial swelling degree. Besides, Western blot assay was used to detect the expression of PI3K/Akt/GSK-3β pathway-related proteins, as well as NOX2 and NLRP3 proteins. Results The results demonstrated that AST pretreatment promoted the hind limb motor function recovery and alleviated the pathological damage induced by SCII. Moreover, AST significantly enhanced the antioxidative stress response and attenuated mitochondrial swelling. However, AST pretreatment hardly inhibited the levels of proinflammatory cytokines after SCII. Most importantly, AST activated p-Akt and p-GSK-3β expression levels. Meanwhile, cotreatment with LY294002 (a PI3K inhibitor) was found to abolish the above protective effects observed with the AST pretreatment. Conclusion Overall, these results suggest that AST pretreatment not only mitigates pathological tissue damage but also effectively improves neural functional recovery following SCII, primarily by alleviating oxidative stress but not inhibiting inflammation. A possible underlying molecular mechanism of AST may be mainly attributed to the activation of PI3K/Akt/GSK-3β pathway.http://link.springer.com/article/10.1186/s13018-020-01790-8Spinal cord ischemia-reperfusion injuryAstaxanthinOxidative stressInflammationApoptosisMitochondria swelling |
| spellingShingle | Jian Fu Haibin Sun Haofei Wei Mingjie Dong Yongzhe Zhang Wei Xu Yanwei Fang Jianhui Zhao Astaxanthin alleviates spinal cord ischemia-reperfusion injury via activation of PI3K/Akt/GSK-3β pathway in rats Journal of Orthopaedic Surgery and Research Spinal cord ischemia-reperfusion injury Astaxanthin Oxidative stress Inflammation Apoptosis Mitochondria swelling |
| title | Astaxanthin alleviates spinal cord ischemia-reperfusion injury via activation of PI3K/Akt/GSK-3β pathway in rats |
| title_full | Astaxanthin alleviates spinal cord ischemia-reperfusion injury via activation of PI3K/Akt/GSK-3β pathway in rats |
| title_fullStr | Astaxanthin alleviates spinal cord ischemia-reperfusion injury via activation of PI3K/Akt/GSK-3β pathway in rats |
| title_full_unstemmed | Astaxanthin alleviates spinal cord ischemia-reperfusion injury via activation of PI3K/Akt/GSK-3β pathway in rats |
| title_short | Astaxanthin alleviates spinal cord ischemia-reperfusion injury via activation of PI3K/Akt/GSK-3β pathway in rats |
| title_sort | astaxanthin alleviates spinal cord ischemia reperfusion injury via activation of pi3k akt gsk 3β pathway in rats |
| topic | Spinal cord ischemia-reperfusion injury Astaxanthin Oxidative stress Inflammation Apoptosis Mitochondria swelling |
| url | http://link.springer.com/article/10.1186/s13018-020-01790-8 |
| work_keys_str_mv | AT jianfu astaxanthinalleviatesspinalcordischemiareperfusioninjuryviaactivationofpi3kaktgsk3bpathwayinrats AT haibinsun astaxanthinalleviatesspinalcordischemiareperfusioninjuryviaactivationofpi3kaktgsk3bpathwayinrats AT haofeiwei astaxanthinalleviatesspinalcordischemiareperfusioninjuryviaactivationofpi3kaktgsk3bpathwayinrats AT mingjiedong astaxanthinalleviatesspinalcordischemiareperfusioninjuryviaactivationofpi3kaktgsk3bpathwayinrats AT yongzhezhang astaxanthinalleviatesspinalcordischemiareperfusioninjuryviaactivationofpi3kaktgsk3bpathwayinrats AT weixu astaxanthinalleviatesspinalcordischemiareperfusioninjuryviaactivationofpi3kaktgsk3bpathwayinrats AT yanweifang astaxanthinalleviatesspinalcordischemiareperfusioninjuryviaactivationofpi3kaktgsk3bpathwayinrats AT jianhuizhao astaxanthinalleviatesspinalcordischemiareperfusioninjuryviaactivationofpi3kaktgsk3bpathwayinrats |