School of Pharmaceutical Science, Shanxi Medical University, No. 56, Xinjian Nan Road, Taiyuan 030001, Shanxi, PR China.
School of Pharmaceutical Science, Shanxi Medical University, No. 56, Xinjian Nan Road, Taiyuan 030001, Shanxi, PR China.
Carbohydr Polym. 2016 Oct 20;151:996-1005. doi: 10.1016/j.carbpol.2016.06.053. Epub 2016 Jun 15.
Dibutyltin (DBT) which was widely used as biocide and plastic stabilizer has been described as a potent neurotoxicant. Chitosan (CS), a natural nontoxic biopolymer, possesses a variety of biological activities including antibacterial, antifungal, free radical scavenging and neuroprotective activities. The present study was undertaken to investigate the protective effects of CS against DBT-induced apoptosis in rat pheochromocytoma (PC12) cells and the underlying mechanisms in vitro. Our results demonstrated that pretreatment with CS significantly increased the cell viability and decreased lactate dehydrogenase (LDH) release induced by DBT in a dose-dependent manner. Meanwhile, DBT-induced cell apoptosis, mitochondrial membrane potential (MMP) disruption, and generation of intracellular reactive oxygen species (ROS) were attenuated by CS. Real-time PCR assay showed that DBT markedly enhanced the mRNA levels of Bax, Bad, cytochrome-c and Apaf-1, reduced the Bcl-2 and Bcl-xL mRNA levels, while these genes expression alteration could be partially reversed by CS treatment. Furthermore, CS also inhibited the DBT-inducted activation of caspase-9, and -3 at mRNA and protein expression levels. Taken together, these results suggested that CS could protect the PC12 cells from apoptosis induced by DBT through inhibition of the mitochondria-dependent pathway.
二丁基锡（DBT）作为一种广泛使用的生物杀灭剂和塑料稳定剂，已被描述为一种有效的神经毒性物质。壳聚糖（CS），一种天然无毒的生物聚合物，具有多种生物学活性，包括抗菌、抗真菌、清除自由基和神经保护活性。本研究旨在探讨 CS 对 DBT 诱导的大鼠嗜铬细胞瘤（PC12）细胞凋亡的保护作用及其在体外的潜在机制。我们的结果表明，CS 预处理可显著增加 DBT 诱导的细胞活力，并呈剂量依赖性降低乳酸脱氢酶（LDH）释放。同时，CS 减弱了 DBT 诱导的细胞凋亡、线粒体膜电位（MMP）破坏和细胞内活性氧（ROS）的产生。实时 PCR 分析显示，DBT 显著增强了 Bax、Bad、细胞色素 c 和 Apaf-1 的 mRNA 水平，降低了 Bcl-2 和 Bcl-xL 的 mRNA 水平，而 CS 处理可部分逆转这些基因的表达改变。此外，CS 还抑制了 DBT 诱导的 caspase-9 和 caspase-3 在 mRNA 和蛋白表达水平的激活。综上所述，这些结果表明 CS 可通过抑制线粒体依赖性途径来保护 PC12 细胞免受 DBT 诱导的凋亡。
