Salvianolic acid B inhibits ototoxic drug–induced ototoxicity by suppression of the mitochondrial apoptosis pathway
Salvianolic acid B inhibits ototoxic drug–induced ototoxicity by suppression of the mitochondrial apoptosis pathway
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DOI：
10.1111/jcmm.15345
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发表时间：
2020-04
影响因子：
5.3
通讯作者：
Zhiwei Zheng;Yunfeng Wang;Huiqian Yu;Wen Li;Jingfang Wu;Chengfu Cai;Yingzi He
中科院分区：
文献类型：
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作者：
Zhiwei Zheng;Yunfeng Wang;Huiqian Yu;Wen Li;Jingfang Wu;Chengfu Cai;Yingzi He
已经声称，丹参素酸B（Sal B），一种天然生物活性抗氧化剂，在各种类型的细胞中发挥保护作用。本研究旨在评价Sal B在培养的HEI-OC 1细胞系和转基因斑马鱼（Brn 3C：EGFP）中的抗氧化和抗凋亡作用。CCK-8试验、Annexin V凋亡检测试剂盒、TUNEL和caspase-3/7染色分别检查了凋亡和细胞活力。通过CellROX和MitoSOX Red染色评价活性氧（ROS）水平。JC-1染色法检测线粒体膜电位（Δ Km）。Western blotting检测Bax和Bcl-2的表达。通过免疫荧光染色确定p-PI 3 K和p-Akt的表达模式。我们发现，Sal B可保护HEI-OC 1细胞免受新霉素和顺铂诱导的凋亡特征，增强细胞活力，并伴有caspase-3活性降低。补充实验确定，Sal B在新霉素和顺铂损伤的HEI-OC 1细胞中减少ROS产生（增加Δ Δ Km），促进Bcl-2表达并下调Bax表达，以及激活PI 3 K/AKT信号通路。此外，Sal B显著降低TUNEL信号，并保护转基因斑马鱼免受新霉素和顺铂诱导的神经肥大HC损失。这些结果揭示了Sal B作为耳保护剂对抗耳毒性药物诱导的HC凋亡的新作用，提供了治疗听力损失的潜在用途。
It has been claimed that salvianolic acid B (Sal B), a natural bioactive antioxidant, exerts protective effects in various types of cells. This study aims to evaluate the antioxidant and anti‐apoptosis effects of Sal B in a cultured HEI‐OC1 cell line and in transgenic zebrafish (Brn3C: EGFP). A CCK‐8 assay, Annexin V Apoptosis Detection Kit, TUNEL and caspase‐3/7 staining, respectively, examined apoptosis and cell viability. The levels of reactive oxygen species (ROS) were evaluated by CellROX and MitoSOX Red staining. JC‐1 staining was employed to detect the mitochondrial membrane potential (ΔΨm). Western blotting was used to assess expressions of Bax and Bcl‐2. The expression pattern of p‐PI3K and p‐Akt was determined by immunofluorescent staining. We found that Sal B protected against neomycin‐ and cisplatin‐induced apoptotic features, enhanced cell viability and accompanied with decreased caspase‐3 activity in the HEI‐OC1 cells. Supplementary experiments determined that Sal B reduced ROS production (increased ΔΨm), promoted Bcl‐2 expression and down‐regulated the expression of Bax, as well as activated PI3K/AKT signalling pathways in neomycin‐ and cisplatin‐injured HEI‐OC1 cells. Moreover, Sal B markedly decreased the TUNEL signal and protected against neomycin‐ and cisplatin‐induced neuromast HC loss in the transgenic zebrafish. These results unravel a novel role for Sal B as an otoprotective agent against ototoxic drug–induced HC apoptosis, offering a potential use in the treatment of hearing loss.