title: Low-dose ribavirin treatments attenuate neuroinflammatory activation of BV-2 Cells by interfering with inducible nitric oxide synthase.
abstract: Microglia play a key role in defending central nervous system from various internal and external threats. However, their excessive and/or chronic activation is associated with deleterious effects in a variety of neurodegenerative diseases. Previously, we have shown that ribavirin when applied in clinically relevant dosage (10 μM) modulates activated microglia in complex fashion inducing both anti- and proinflammatory effects, simultaneously causing cytotoxicity. Here, we examined potential of low-dose ribavirin (0.1 and 1 μM) to modulate activated BV-2 microglia. Morphological and functional activation of BV-2 cells was achieved with lipopolysaccharide (LPS) stimulation. Our results demonstrated that low-dose ribavirin did not induce cell death, while 10 μM ribavirin promoted LPS induced apoptosis. We determined that 1 μM ribavirin was equally efficient in deactivation of LPS induced morphological changes as 10 μM ribavirin treatment. Ribavirin showed halfway success in reducing markers of functional activation of microglia. Namely, none of the doses had effect on LPS triggered production of proinflammatory cytokine tumor necrosis factor alpha. On the other hand, low-dose ribavirin proved its effectiveness in reduction of another inflammatory mediator, nitric oxide, by inhibiting inducible form of nitric oxide synthase. Our results imply that low-dose ribavirin may alleviate nitrosative stress during neuroinflammation.
authors.affiliation: Department of Neurobiology, Institute for Biological Research "Sinisa Stankovic", University of Belgrade, Boulevard Despot Stefan 142, Belgrade 11060, Serbia.
authors.forename: Iva
authors.initials: I
authors.lastname: Bozic
authors.affiliation: Department of Neurobiology, Institute for Biological Research "Sinisa Stankovic", University of Belgrade, Boulevard Despot Stefan 142, Belgrade 11060, Serbia.
authors.forename: Danijela
authors.initials: D
authors.lastname: Savic
authors.affiliation: Department of Neurobiology, Institute for Biological Research "Sinisa Stankovic", University of Belgrade, Boulevard Despot Stefan 142, Belgrade 11060, Serbia.
authors.forename: Marija
authors.initials: M
authors.lastname: Jovanovic
authors.affiliation: Department of Neurobiology, Institute for Biological Research "Sinisa Stankovic", University of Belgrade, Boulevard Despot Stefan 142, Belgrade 11060, Serbia.
authors.forename: Ivana
authors.initials: I
authors.lastname: Bjelobaba
authors.affiliation: Institute of Physiology and Biochemistry, Faculty of Biology, University of Belgrade, Studentski Trg 3, Belgrade 11001, Serbia.
authors.forename: Danijela
authors.initials: D
authors.lastname: Laketa
authors.affiliation: Institute of Physiology and Biochemistry, Faculty of Biology, University of Belgrade, Studentski Trg 3, Belgrade 11001, Serbia.
authors.forename: Nadezda
authors.initials: N
authors.lastname: Nedeljkovic
authors.affiliation: Department of Neurobiology, Institute for Biological Research "Sinisa Stankovic", University of Belgrade, Boulevard Despot Stefan 142, Belgrade 11060, Serbia.
authors.forename: Mirjana
authors.initials: M
authors.lastname: Stojiljkovic
authors.affiliation: Department of Neurobiology, Institute for Biological Research "Sinisa Stankovic", University of Belgrade, Boulevard Despot Stefan 142, Belgrade 11060, Serbia.
authors.forename: Sanja
authors.initials: S
authors.lastname: Pekovic
authors.affiliation: Department of Neurobiology, Institute for Biological Research "Sinisa Stankovic", University of Belgrade, Boulevard Despot Stefan 142, Belgrade 11060, Serbia.
authors.forename: Irena
authors.initials: I
authors.lastname: Lavrnja
mesh_terms: D000818:Animals; D017304:Annexin A5 / Q000378:metabolism; D048430:Cell Shape / Q000187:drug effects; D002470:Cell Survival / Q000187:drug effects; D003599:Cytoskeleton / Q000187:drug effects / Q000378:metabolism; D004305:Dose-Response Relationship, Drug; D005434:Flow Cytometry; D007249:Inflammation / Q000473:pathology*; D008070:Lipopolysaccharides; D051379:Mice; D017628:Microglia / Q000187:drug effects / Q000201:enzymology* / Q000473:pathology*; D009569:Nitric Oxide / Q000378:metabolism; D052247:Nitric Oxide Synthase Type II / Q000378:metabolism*; D011419:Propidium / Q000378:metabolism; D012254:Ribavirin / Q000494:pharmacology*; D014409:Tumor Necrosis Factor-alpha / Q000096:biosynthesis
chemical_list: D017304:Annexin A5; D008070:Lipopolysaccharides; D014409:Tumor Necrosis Factor-alpha; D009569:Nitric Oxide; D011419:Propidium; D012254:Ribavirin; D052247:Nitric Oxide Synthase Type II