title: Prophylactic Chronic Zinc Administration Increases Neuroinflammation in a Hypoxia-Ischemia Model.
abstract: Acute and subacute administration of zinc exert neuroprotective effects in hypoxia-ischemia animal models; yet the effect of chronic administration of zinc still remains unknown. We addressed this issue by injecting zinc at a tolerable dose (0.5 mg/kg weight, i.p.) for 14 days before common carotid artery occlusion (CCAO) in a rat. After CCAO, the level of zinc was measured by atomic absorption spectrophotometry, nitrites were determined by Griess method, lipoperoxidation was measured by Gerard-Monnier assay, and mRNA expression of 84 genes coding for cytokines, chemokines, and their receptors was measured by qRT-PCR, whereas nitrotyrosine, chemokines, and their receptors were assessed by ELISA and histopathological changes in the temporoparietal cortex-hippocampus at different time points. Long-term memory was evaluated using Morris water maze. Following CCAO, a significant increase in nitrosative stress, inflammatory chemokines/receptors, and cell death was observed after 8 h, and a 2.5-fold increase in zinc levels was detected after 7 days. Although CXCL12 and FGF2 protein levels were significantly increased, the long-term memory was impaired 12 days after reperfusion in the Zn+CCAO group. Our data suggest that the chronic administration of zinc at tolerable doses causes nitrosative stress, toxic zinc accumulation, and neuroinflammation, which might account for the neuronal death and cerebral dysfunction after CCAO.
authors.affiliation: Facultad de Ciencias Químicas, Benemérita Universidad Autonoma de Puebla, 14 Sur y Avenida San Claudio, 72570 Puebla, PUE, Mexico.
authors.forename: Constantino
authors.initials: C
authors.lastname: Tomas-Sanchez
authors.affiliation: Facultad de Ciencias Químicas, Benemérita Universidad Autonoma de Puebla, 14 Sur y Avenida San Claudio, 72570 Puebla, PUE, Mexico.
authors.forename: Victor Manuel
authors.initials: VM
authors.lastname: Blanco-Alvarez
authors.affiliation: Laboratorio de Medicina Genómica, Hospital Regional 1° de Octubre, ISSSTE, Avenida Instituto Politécnico Nacional, No. 1669, 07760 Ciudad de México, Mexico.
authors.forename: Juan Antonio
authors.initials: JA
authors.lastname: Gonzalez-Barrios
authors.affiliation: Departamento de Fisiología, Biofísica y Neurociencias, Centro de Investigación y de Estudios Avanzados del Instituto Politécnico Nacional, Apartado Postal 14-740, 07000 Ciudad de México, Mexico.
authors.forename: Daniel
authors.initials: D
authors.lastname: Martinez-Fong
authors.affiliation: Facultad de Ciencias Químicas, Benemérita Universidad Autonoma de Puebla, 14 Sur y Avenida San Claudio, 72570 Puebla, PUE, Mexico.
authors.forename: Guadalupe
authors.initials: G
authors.lastname: Garcia-Robles
authors.affiliation: Departamento de Fisiología, Biofísica y Neurociencias, Centro de Investigación y de Estudios Avanzados del Instituto Politécnico Nacional, Apartado Postal 14-740, 07000 Ciudad de México, Mexico.
authors.forename: Guadalupe
authors.initials: G
authors.lastname: Soto-Rodriguez
authors.affiliation: Facultad de Ciencias Químicas, Benemérita Universidad Autonoma de Puebla, 14 Sur y Avenida San Claudio, 72570 Puebla, PUE, Mexico.
authors.forename: Eduardo
authors.identifier: 0000-0003-0377-0943
authors.initials: E
authors.lastname: Brambila
authors.affiliation: Facultad de Ciencias Químicas, Benemérita Universidad Autonoma de Puebla, 14 Sur y Avenida San Claudio, 72570 Puebla, PUE, Mexico.
authors.forename: Maricela
authors.initials: M
authors.lastname: Torres-Soto
authors.affiliation: Facultad de Ciencias Químicas, Benemérita Universidad Autonoma de Puebla, 14 Sur y Avenida San Claudio, 72570 Puebla, PUE, Mexico.
authors.forename: Alejandro
authors.initials: A
authors.lastname: Gonzalez-Vazquez
authors.affiliation: Facultad de Ciencias Químicas, Benemérita Universidad Autonoma de Puebla, 14 Sur y Avenida San Claudio, 72570 Puebla, PUE, Mexico.
authors.forename: Ana Karina
authors.initials: AK
authors.lastname: Aguilar-Peralta
authors.affiliation: Facultad de Ciencias Químicas, Benemérita Universidad Autonoma de Puebla, 14 Sur y Avenida San Claudio, 72570 Puebla, PUE, Mexico.
authors.forename: José-Luis
authors.initials: JL
authors.lastname: Garate-Morales
authors.affiliation: Facultad de Ciencias Químicas, Benemérita Universidad Autonoma de Puebla, 14 Sur y Avenida San Claudio, 72570 Puebla, PUE, Mexico.
authors.forename: Luis-Angel
authors.initials: LA
authors.lastname: Aguilar-Carrasco
authors.affiliation: Facultad de Ciencias Químicas, Benemérita Universidad Autonoma de Puebla, 14 Sur y Avenida San Claudio, 72570 Puebla, PUE, Mexico.
authors.forename: Daniel I
authors.initials: DI
authors.lastname: Limón
authors.affiliation: Facultad de Medicina, Benemérita Universidad Autonoma de Puebla, 13 Sur 3101, 72420 Puebla, PUE, Mexico.
authors.forename: Jorge
authors.initials: J
authors.lastname: Cebada
authors.affiliation: Facultad de Ciencias Químicas, Benemérita Universidad Autonoma de Puebla, 14 Sur y Avenida San Claudio, 72570 Puebla, PUE, Mexico.
authors.forename: Bertha Alicia
authors.identifier: 0000-0002-8041-9404
authors.initials: BA
authors.lastname: Leon-Chavez
mesh_terms: D000818:Animals; D018925:Chemokines / Q000235:genetics / Q000378:metabolism; D002712:Chlorides / Q000008:administration & dosage* / Q000378:metabolism / Q000633:toxicity*; D004195:Disease Models, Animal; D004334:Drug Administration Schedule; D016222:Fibroblast Growth Factor 2 / Q000097:blood; D006624:Hippocampus / Q000187:drug effects / Q000503:physiopathology; D020925:Hypoxia-Ischemia, Brain / Q000188:drug therapy / Q000276:immunology / Q000503:physiopathology*; D008297:Male; D018782:Maze Learning / Q000187:drug effects; D008568:Memory / Q000187:drug effects; D015213:Neuroimmunomodulation / Q000187:drug effects*; D009474:Neurons / Q000378:metabolism; D018696:Neuroprotective Agents / Q000008:administration & dosage* / Q000378:metabolism / Q000633:toxicity; D009573:Nitrites / Q000378:metabolism; D051381:Rats; D017208:Rats, Wistar; D019707:Receptors, Chemokine / Q000235:genetics / Q000378:metabolism; D017967:Zinc Compounds / Q000008:administration & dosage* / Q000378:metabolism / Q000633:toxicity*
chemical_list: D018925:Chemokines; D002712:Chlorides; D018696:Neuroprotective Agents; D009573:Nitrites; D019707:Receptors, Chemokine; D017967:Zinc Compounds; D016222:Fibroblast Growth Factor 2; C016837:zinc chloride