title: Mechanisms of beauvericin toxicity and antioxidant cellular defense.
abstract: Beauvericin (BEA) is a secondary metabolite produced by many species of fungus Fusarium. This study determines the injury (cell viability, cell proliferation, mitochondrial membrane potential, cell death and DNA damage) and the intracellular defense mechanisms (catalase and superoxide dismutase) in Chinese Hamster ovary (CHO-K1) cells after BEA exposure. The results obtained in this study demonstrated that BEA induces cytotoxicity in a dose- and time-dependent manner in CHO-K1 cells. Moreover, disruption in mitochondrial enzymatic activity and cell proliferation has been observed after BEA exposure, which can lead or be consequence of cell death. BEA inhibits cell proliferation by arresting cells in G0/G1 and increasing apoptosis. Moreover, at higher exposure times, BEA induces differentiation of CHO-K1 cells through G2/M arrest, preventing that cells entry into mitosis. DNA strand breaks were observed at 1 μM after 24h of exposure. On the other hand, the SOD and CAT activities were increased after BEA exposure and as a defense system they could contribute to eliminate damage produced by BEA and oxidants products generated in CHO-K1 cells.
authors.affiliation: Laboratory of Toxicology, Faculty of Pharmacy, University of Valencia, Av. Vicent Andres Estelles s/n, 46100 Burjassot, Valencia, Spain. Electronic address: beatriz.mallebrera@uv.es.
authors.forename: Beatriz
authors.initials: B
authors.lastname: Mallebrera
authors.affiliation: Laboratory of Toxicology, Faculty of Pharmacy, University of Valencia, Av. Vicent Andres Estelles s/n, 46100 Burjassot, Valencia, Spain.
authors.forename: Ana
authors.initials: A
authors.lastname: Juan-Garcia
authors.affiliation: Laboratory of Toxicology, Faculty of Pharmacy, University of Valencia, Av. Vicent Andres Estelles s/n, 46100 Burjassot, Valencia, Spain.
authors.forename: Guillermina
authors.initials: G
authors.lastname: Font
authors.affiliation: Laboratory of Toxicology, Faculty of Pharmacy, University of Valencia, Av. Vicent Andres Estelles s/n, 46100 Burjassot, Valencia, Spain.
authors.forename: Maria-Jose
authors.initials: MJ
authors.lastname: Ruiz
mesh_terms: D000818:Animals; D000975:Antioxidants / Q000378:metabolism*; D017209:Apoptosis / Q000187:drug effects; D016466:CHO Cells; D002374:Catalase / Q000378:metabolism*; D049109:Cell Proliferation / Q000187:drug effects; D002470:Cell Survival / Q000187:drug effects; D003412:Cricetulus; D004249:DNA Damage / Q000187:drug effects; D047630:Depsipeptides / Q000633:toxicity*; D053078:Membrane Potential, Mitochondrial / Q000187:drug effects; D013482:Superoxide Dismutase / Q000378:metabolism*
chemical_list: D000975:Antioxidants; D047630:Depsipeptides; C004456:beauvericin; D002374:Catalase; D013482:Superoxide Dismutase
keywords: Beauvericin; Cell death; Cytotoxicity; DNA damage; Defense mechanisms; Mitochondrial membrane potential