L-3-n-butylphthalide alleviates intermittent alcohol exposure-induced hypothalamic cell apoptosis via inhibiting the IRE1α-ASK1-JNK pathway in adolescent rats
Exposure to alcohol can induce different degrees of damage to various tissues and organs, and brain is the most vulnerable part affected by alcohol. However, there is no detailed report on whether intermittent alcohol exposure can result in pathological changes in the hypothalamus of adolescent rats...
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Elsevier
2025-01-01
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| Series: | Current Research in Toxicology |
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| Online Access: | http://www.sciencedirect.com/science/article/pii/S2666027X24000641 |
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| author | Shanyong Yi Lai Wei Bin Zhao Zhijun Yao Bin Yang |
| author_facet | Shanyong Yi Lai Wei Bin Zhao Zhijun Yao Bin Yang |
| author_sort | Shanyong Yi |
| collection | DOAJ |
| description | Exposure to alcohol can induce different degrees of damage to various tissues and organs, and brain is the most vulnerable part affected by alcohol. However, there is no detailed report on whether intermittent alcohol exposure can result in pathological changes in the hypothalamus of adolescent rats and the detailed mechanism. This study investigated pathological changes in the hypothalamus, probed the levels of inflammatory factors, and detected the expression of proteins related to endoplasmic reticulum stress (ERS) to determine whether ERS is involved in the injury process of the hypothalamus and the protective mechanism of L-3-n-butylphthalide (L-NBP). The results showed that intermittent alcohol exposure induced hypothalamic nerve injury, including cell apoptosis, increased the levels of inflammatory factors, and upregulated the expression of glucose-regulated protein 78 (GRP78), p-Inositol Requiring Enzyme 1α (p-IRE1α), apoptosis signal-regulating kinase 1 (ASK1), and p-c-Jun N-terminal kinase (p-JNK)). Tauroursodeoxycholic acid (TUDCA), an ERS inhibitor, significantly reduced the pathological damage described above. The increases in the levels of inflammatory factors, pathological injury, and increased levels of proteins associated with the IRE1α-ASK1-JNK pathway were alleviated by L-NBP. The present study indicated that intermittent alcohol exposure could lead to hypothalamic cell apoptosis in adolescent rats and L-NBP could alleviate the above injury by inhibiting the IRE1α-ASK1-JNK pathway.Abbreviations: Ang-2, Angiopoietin-2; ASK1, Apoptosis signal-regulating kinase 1; ER, Endoplasmic reticulum; ERS, Endoplasmic reticulum stress; ELISA, Enzyme-linked immunosorbent assay; GFAP, Glial fibrillary acidic protein; GRP78, Glucose-regulated protein 78; IBA1, Ionized calcium binding adapter molecule 1; i.p., Intraperitoneal; IRE1α, Inositol Requiring Enzyme 1α; JNK, c-Jun N-terminal kinase; L-NBP, L-3-n-butylphthalide; PND, Postnatal day; PVDF, Polyvinylidene difluoride; SDS-PAGE, Sodium dodecyl sulfate–polyacrylamide gel electrophoresis; TRAF2, TNF-receptor associated factor 2; TUDCA, Tauroursodeoxycholic acid; VEGF, Vascular endothelial growth factor. |
| format | Article |
| id | doaj-art-941ca86cfbc941638c8c251449a625ab |
| institution | Kabale University |
| issn | 2666-027X |
| language | English |
| publishDate | 2025-01-01 |
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| series | Current Research in Toxicology |
| spelling | doaj-art-941ca86cfbc941638c8c251449a625ab2024-12-28T05:22:48ZengElsevierCurrent Research in Toxicology2666-027X2025-01-018100211L-3-n-butylphthalide alleviates intermittent alcohol exposure-induced hypothalamic cell apoptosis via inhibiting the IRE1α-ASK1-JNK pathway in adolescent ratsShanyong Yi0Lai Wei1Bin Zhao2Zhijun Yao3Bin Yang4Xinxiang Key Laboratory of Forensic Toxicology, School of Forensic Medicine, Xinxiang Medical University, Xinxiang 453002, Henan, China; Corresponding authors.Xinxiang Key Laboratory of Forensic Toxicology, School of Forensic Medicine, Xinxiang Medical University, Xinxiang 453002, Henan, ChinaXinxiang Key Laboratory of Forensic Toxicology, School of Forensic Medicine, Xinxiang Medical University, Xinxiang 453002, Henan, ChinaXinxiang Key Laboratory of Forensic Toxicology, School of Forensic Medicine, Xinxiang Medical University, Xinxiang 453002, Henan, ChinaHenan Key Laboratory of Biological Psychiatry (Xinxiang Medical University), The Second Affiliated Hospital of Xinxiang Medical University (Henan Mental Hospital), Xinxiang 453002, Henan, China; Corresponding authors.Exposure to alcohol can induce different degrees of damage to various tissues and organs, and brain is the most vulnerable part affected by alcohol. However, there is no detailed report on whether intermittent alcohol exposure can result in pathological changes in the hypothalamus of adolescent rats and the detailed mechanism. This study investigated pathological changes in the hypothalamus, probed the levels of inflammatory factors, and detected the expression of proteins related to endoplasmic reticulum stress (ERS) to determine whether ERS is involved in the injury process of the hypothalamus and the protective mechanism of L-3-n-butylphthalide (L-NBP). The results showed that intermittent alcohol exposure induced hypothalamic nerve injury, including cell apoptosis, increased the levels of inflammatory factors, and upregulated the expression of glucose-regulated protein 78 (GRP78), p-Inositol Requiring Enzyme 1α (p-IRE1α), apoptosis signal-regulating kinase 1 (ASK1), and p-c-Jun N-terminal kinase (p-JNK)). Tauroursodeoxycholic acid (TUDCA), an ERS inhibitor, significantly reduced the pathological damage described above. The increases in the levels of inflammatory factors, pathological injury, and increased levels of proteins associated with the IRE1α-ASK1-JNK pathway were alleviated by L-NBP. The present study indicated that intermittent alcohol exposure could lead to hypothalamic cell apoptosis in adolescent rats and L-NBP could alleviate the above injury by inhibiting the IRE1α-ASK1-JNK pathway.Abbreviations: Ang-2, Angiopoietin-2; ASK1, Apoptosis signal-regulating kinase 1; ER, Endoplasmic reticulum; ERS, Endoplasmic reticulum stress; ELISA, Enzyme-linked immunosorbent assay; GFAP, Glial fibrillary acidic protein; GRP78, Glucose-regulated protein 78; IBA1, Ionized calcium binding adapter molecule 1; i.p., Intraperitoneal; IRE1α, Inositol Requiring Enzyme 1α; JNK, c-Jun N-terminal kinase; L-NBP, L-3-n-butylphthalide; PND, Postnatal day; PVDF, Polyvinylidene difluoride; SDS-PAGE, Sodium dodecyl sulfate–polyacrylamide gel electrophoresis; TRAF2, TNF-receptor associated factor 2; TUDCA, Tauroursodeoxycholic acid; VEGF, Vascular endothelial growth factor.http://www.sciencedirect.com/science/article/pii/S2666027X24000641L-3-n-butylphthalide (L-NBP)IRE1α-ASK1-JNK pathwayIntermittent alcohol exposureAdolescent ratsApoptosis |
| spellingShingle | Shanyong Yi Lai Wei Bin Zhao Zhijun Yao Bin Yang L-3-n-butylphthalide alleviates intermittent alcohol exposure-induced hypothalamic cell apoptosis via inhibiting the IRE1α-ASK1-JNK pathway in adolescent rats Current Research in Toxicology L-3-n-butylphthalide (L-NBP) IRE1α-ASK1-JNK pathway Intermittent alcohol exposure Adolescent rats Apoptosis |
| title | L-3-n-butylphthalide alleviates intermittent alcohol exposure-induced hypothalamic cell apoptosis via inhibiting the IRE1α-ASK1-JNK pathway in adolescent rats |
| title_full | L-3-n-butylphthalide alleviates intermittent alcohol exposure-induced hypothalamic cell apoptosis via inhibiting the IRE1α-ASK1-JNK pathway in adolescent rats |
| title_fullStr | L-3-n-butylphthalide alleviates intermittent alcohol exposure-induced hypothalamic cell apoptosis via inhibiting the IRE1α-ASK1-JNK pathway in adolescent rats |
| title_full_unstemmed | L-3-n-butylphthalide alleviates intermittent alcohol exposure-induced hypothalamic cell apoptosis via inhibiting the IRE1α-ASK1-JNK pathway in adolescent rats |
| title_short | L-3-n-butylphthalide alleviates intermittent alcohol exposure-induced hypothalamic cell apoptosis via inhibiting the IRE1α-ASK1-JNK pathway in adolescent rats |
| title_sort | l 3 n butylphthalide alleviates intermittent alcohol exposure induced hypothalamic cell apoptosis via inhibiting the ire1α ask1 jnk pathway in adolescent rats |
| topic | L-3-n-butylphthalide (L-NBP) IRE1α-ASK1-JNK pathway Intermittent alcohol exposure Adolescent rats Apoptosis |
| url | http://www.sciencedirect.com/science/article/pii/S2666027X24000641 |
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