title: Contribution of nano-copper particles to in vivo liver dysfunction and cellular damage: role of IκBα/NF-κB, MAPKs and mitochondrial signal.
abstract: The present study investigated the oxidative stress responsive cell signaling in nano-copper-induced hepatic dysfunction and cell death. Exposure to nano-copper (18 nm) dose-dependently (200-600 mg/kg bw) reduced the hepatic index, caused oxidative stress and led to hepatic dysfunction. Nano-copper burden also increased the transcriptional activity of NF-κB, up-regulated the expression of phosphorylated p38, ERK1/2 and caused the reciprocal regulation of Bcl-2 family proteins, disruption of mitochondrial membrane potential, release of cytochrome C, formation of apoptosome and activation of caspase 3. DAPI staining, immunofluorescence study, FACS analysis and histological findings also support this observation. Soluble copper (Cu(+2), 110 mg/kg bw)-exposed animals were used as a positive control. Different doses of particulate and soluble forms were used in the study because of different LD(50) values. The results suggest that nano-copper induces hepatic dysfunction and cell death via the oxidative stress-dependent signaling cascades and mitochondrial event.
authors.affiliation: Division of Molecular Medicine, Bose Institute, Calcutta, West Bengal, India.
authors.forename: Prasenjit
authors.initials: P
authors.lastname: Manna
authors.forename: Manoranjan
authors.initials: M
authors.lastname: Ghosh
authors.forename: Jyotirmoy
authors.initials: J
authors.lastname: Ghosh
authors.forename: Joydeep
authors.initials: J
authors.lastname: Das
authors.forename: Parames C
authors.initials: PC
authors.lastname: Sil
mesh_terms: D000818:Animals; D056486:Chemical and Drug Induced Liver Injury / Q000209:etiology* / Q000378:metabolism / Q000473:pathology; D003300:Copper / Q000633:toxicity; D019327:Copper Sulfate / Q000633:toxicity*; D004305:Dose-Response Relationship, Drug; D022781:Hepatocytes / Q000187:drug effects / Q000378:metabolism; D020672:I-kappa B Proteins / Q000378:metabolism*; D008297:Male; D053768:Metal Nanoparticles / Q000633:toxicity*; D051379:Mice; D008928:Mitochondria / Q000187:drug effects* / Q000378:metabolism; D020928:Mitogen-Activated Protein Kinases / Q000378:metabolism*; D016328:NF-kappa B / Q000378:metabolism*; D018384:Oxidative Stress / Q000187:drug effects; D015398:Signal Transduction / Q000187:drug effects; D018675:Toxicity Tests
chemical_list: D020672:I-kappa B Proteins; D016328:NF-kappa B; D003300:Copper; D020928:Mitogen-Activated Protein Kinases; D019327:Copper Sulfate; C029892:cupric chloride