title: Atorvastatin protected from paraquat-induced cytotoxicity in alveolar macrophages via down-regulation of TLR-4.
abstract: The current study designed to clarify the mechanism of paraquat-induced cytotoxicity and protective effects of Atorvastatin on freshly isolated alveolar macrophages (AMs). AMs were collected via bronchoalveolar lavage and exposed to various concentrations of paraquat in the presence and absence of atorvastatin for 24h. Cell viability, myeloperoxidase activity; nitric oxide generation and total antioxidant capacity were assessed. Expression of TLR-4 at mRNA and protein levels were studied by using PCR and western blot methods Atorvastatin enhanced the paraquat-reduced cell viability and reduced the paraquat-induced myeloperoxidase activity and nitric oxide production. Moreover, atorvastatin down-regulated by 60% the paraquat up-regulated expression of TLR-4 at protein and mRNA level. Our results suggest that, AMs in vitro model could be a novel cytological tool for studies on paraquat poisoning and therapy regimens. Additionally, atorvastatin cytoprotective effects on paraquat-induced cytotoxicity partly attribute to its anti-myeloperoxidase, antioxidant properties, which might be regulated via TLR-4 expression.
authors.affiliation: Department of Pharmacology & Toxicology, Faculty of Veterinary Medicine, Urmia University, Urmia, Iran.
authors.forename: Nazli
authors.initials: N
authors.lastname: Alizadeh-Tabrizi
authors.affiliation: Department of Pharmacology & Toxicology, Faculty of Veterinary Medicine, Urmia University, Urmia, Iran; Department of Pharmacology and Toxicology, Faculty of Pharmacy, Urmia Medical University of Sciences, Urmia, Iran. Electronic address: hassanmalekinejad@yahoo.com.
authors.forename: Hassan
authors.initials: H
authors.lastname: Malekinejad
authors.affiliation: Faculty of Science, Institute for Pharmaceutical Sciences, Utrecht University, Utrecht, The Netherlands.
authors.forename: Soheil
authors.initials: S
authors.lastname: Varasteh
authors.affiliation: Department of Pharmacology & Toxicology, Faculty of Veterinary Medicine, Urmia University, Urmia, Iran.
authors.forename: Hadi
authors.initials: H
authors.lastname: Cheraghi
mesh_terms: D000818:Animals; D000893:Anti-Inflammatory Agents / Q000494:pharmacology*; D000975:Antioxidants / Q000494:pharmacology*; D000069059:Atorvastatin / Q000494:pharmacology*; D002470:Cell Survival / Q000187:drug effects; D002478:Cells, Cultured; D015536:Down-Regulation; D006540:Herbicides / Q000633:toxicity*; D019161:Hydroxymethylglutaryl-CoA Reductase Inhibitors / Q000494:pharmacology; D016676:Macrophages, Alveolar / Q000187:drug effects* / Q000378:metabolism; D008297:Male; D009569:Nitric Oxide / Q000378:metabolism; D010269:Paraquat / Q000633:toxicity*; D009195:Peroxidase / Q000378:metabolism; D051381:Rats; D051197:Toll-Like Receptor 4 / Q000235:genetics / Q000378:metabolism
chemical_list: D000893:Anti-Inflammatory Agents; D000975:Antioxidants; D006540:Herbicides; D019161:Hydroxymethylglutaryl-CoA Reductase Inhibitors; C495347:Tlr4 protein, rat; D051197:Toll-Like Receptor 4; D009569:Nitric Oxide; D000069059:Atorvastatin; D009195:Peroxidase; D010269:Paraquat
keywords: Alveolar macrophages; Atorvastatin; Cytotoxicity; Paraquat; Toll like receptor-4