title: Alpha-lipoic acid protects against cadmium-induced hepatotoxicity via calcium signalling and gap junctional intercellular communication in rat hepatocytes.
abstract: This study investigated the protective effect of alpha-lipoic acid (LA) on cadmium (Cd)-induced hepatotoxicity in BRL 3A rat liver cells. We demonstrated that LA ameliorated Cd-induced cellular injury in cell viability and nuclear fragmentation in BRL 3A cells. Furthermore, LA markedly ameliorated Cd-induced gap junctional intercellular communication (GJIC) inhibition and Cx43 mRNA expression decrease, as well as disassembly of gap junctions. The gap junction blocker carbenoxolone disodium (CBX) as well as LA protected healthy cells from Cd-exposed cells in Transwell co-culture system. LA also protected BRL 3A cells against Cd-induced elevation of the intracellular concentration of free calcium ([Ca(2+)]i). Pretreatment with a chelater of intracellular Ca(2+) BAPTA-AM or chelater of extracellular Ca(2+) EGTA attenuated Cd-induced cytotoxicity and GJIC inhibition. CBX exacerbated the decrease in cell viability and further elevated the increase in [Ca(2+)]i induced by Cd, whereas BAPTA-AM partly attenuated these phenomena, while EGTA had little effects. These results suggested that Cd-induced hepatotoxicity via GJIC inhibition and [Ca(2+)]i elevation, which originates mainly from intracellular stores. GJIC inhibition has dual effects: (i) it restricts release of Ca(2+) from the cell, which exacerbates the [Ca(2+)]i elevation and cytotoxicity induced by Cd; and (ii) it protects healthy cells from their dangerous neighbors by blocking intercellular communication. Above all, our results indicated that LA partly prevented Cd-induced cytotoxicity via GJIC and calcium signaling in BRL 3A rat liver cells.
authors.affiliation: College of Veterinary Medicine, Yangzhou University, and Jiangsu Co-innovation Center for Prevention and Control of Important Animal Infectious Diseases and Zoonoses, China.
authors.forename: Hui
authors.initials: H
authors.lastname: Zou
authors.forename: Xuezhong
authors.initials: X
authors.lastname: Liu
authors.forename: Tao
authors.initials: T
authors.lastname: Han
authors.forename: Di
authors.initials: D
authors.lastname: Hu
authors.forename: Yan
authors.initials: Y
authors.lastname: Yuan
authors.forename: Jianhong
authors.initials: J
authors.lastname: Gu
authors.forename: Jianchun
authors.initials: J
authors.lastname: Bian
authors.forename: Zongping
authors.initials: Z
authors.lastname: Liu
mesh_terms: D000818:Animals; D002104:Cadmium / Q000633:toxicity*; D002118:Calcium / Q000378:metabolism; D020013:Calcium Signaling / Q000187:drug effects*; D002450:Cell Communication / Q000187:drug effects*; D002470:Cell Survival / Q000187:drug effects; D002478:Cells, Cultured; D017629:Gap Junctions / Q000187:drug effects* / Q000502:physiology; D022781:Hepatocytes / Q000187:drug effects* / Q000502:physiology; D051381:Rats; D008063:Thioctic Acid / Q000494:pharmacology*
chemical_list: D002104:Cadmium; D008063:Thioctic Acid; D002118:Calcium