title: Chitosan attenuates dibutyltin-induced apoptosis in PC12 cells through inhibition of the mitochondria-dependent pathway.
abstract: 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.
authors.affiliation: School of Pharmaceutical Science, Shanxi Medical University, No. 56, Xinjian Nan Road, Taiyuan 030001, Shanxi, PR China.
authors.forename: Xiaorui
authors.initials: X
authors.lastname: Wang
authors.affiliation: School of Pharmaceutical Science, Shanxi Medical University, No. 56, Xinjian Nan Road, Taiyuan 030001, Shanxi, PR China.
authors.forename: Junqiu
authors.initials: J
authors.lastname: Miao
authors.affiliation: School of Pharmaceutical Science, Shanxi Medical University, No. 56, Xinjian Nan Road, Taiyuan 030001, Shanxi, PR China.
authors.forename: Chaoqun
authors.initials: C
authors.lastname: Yan
authors.affiliation: School of Pharmaceutical Science, Shanxi Medical University, No. 56, Xinjian Nan Road, Taiyuan 030001, Shanxi, PR China.
authors.forename: Rui
authors.initials: R
authors.lastname: Ge
authors.affiliation: School of Pharmaceutical Science, Shanxi Medical University, No. 56, Xinjian Nan Road, Taiyuan 030001, Shanxi, PR China. Electronic address: ltaigang@163.com.
authors.forename: Taigang
authors.initials: T
authors.lastname: Liang
authors.affiliation: School of Pharmaceutical Science, Shanxi Medical University, No. 56, Xinjian Nan Road, Taiyuan 030001, Shanxi, PR China.
authors.forename: Enli
authors.initials: E
authors.lastname: Liu
authors.affiliation: School of Pharmaceutical Science, Shanxi Medical University, No. 56, Xinjian Nan Road, Taiyuan 030001, Shanxi, PR China. Electronic address: sxyxlqs@163.com.
authors.forename: Qingshan
authors.initials: Q
authors.lastname: Li
mesh_terms: D000818:Animals; D017209:Apoptosis / Q000187:drug effects*; D048271:Chitosan / Q000494:pharmacology*; D019610:Cytoprotection / Q000187:drug effects; D005786:Gene Expression Regulation / Q000187:drug effects; D053078:Membrane Potential, Mitochondrial / Q000187:drug effects; D008928:Mitochondria / Q000187:drug effects*; D009498:Neurotoxins / Q000633:toxicity*; D009947:Organotin Compounds / Q000633:toxicity*; D016716:PC12 Cells; D051381:Rats; D017382:Reactive Oxygen Species / Q000378:metabolism
chemical_list: D009498:Neurotoxins; D009947:Organotin Compounds; D017382:Reactive Oxygen Species; C056189:di-n-butyltin; D048271:Chitosan
keywords: Apoptosis; Chitosan; Dibutyltin; Mitochondria-dependent pathway; PC12 cells