title: Zinc and magnesium ions synergistically inhibit superoxide generation by cultured human neutrophils--a promising candidate formulation for amnioinfusion fluid.
abstract: Oligohydramnios is often caused by the premature rupturing of membranes and subsequent intrauterine infections, such as chorioamnionitis, in which event oxidative stress is hypothesized to be closely associated with the damage to the fetal organs. The clinical efficiency of amnioinfusion using warmed saline in cases of premature rupture of membranes is still controversial, especially concerning the prognosis for the fetus. In the present study, we found that human amniotic fluid per se suppresses the release of superoxide from cultured human neutrophils, suggesting an acute or chronic shortage of amniotic fluid in cases of premature rupture of membranes can affect the shielding of intrauterine organs from oxidative stress. The aim of this study was to propose a formula of zinc and magnesium ions in saline for amnioinfusion, by assessing antioxidative activities. A combination of 5 microM zinc and 5mM magnesium in saline synergistically inhibited superoxide production by cultured human neutrophils, equivalent to human amniotic fluid. The intraperitoneal administration of this formula significantly improved the survival rate in a rat model of peritonitis compared to the saline control (46.7% vs. 10%). The combination of these metals with saline may thus be a promising formula for an amnioinfusion fluid with the capacity to protect fetal organs from oxidative stress.
authors.affiliation: Department of Obstetrics and Gynecology, Hamamatsu University School of Medicine, 1-20-1 Handayama, Higashi-ku, Hamamatsu 431-3192, Japan.
authors.forename: Toshiyuki
authors.initials: T
authors.lastname: Uchida
authors.forename: Hiroaki
authors.initials: H
authors.lastname: Itoh
authors.forename: Yuki
authors.initials: Y
authors.lastname: Nakamura
authors.forename: Yukiko
authors.initials: Y
authors.lastname: Kobayashi
authors.forename: Kyuya
authors.initials: K
authors.lastname: Hirai
authors.forename: Kazunao
authors.initials: K
authors.lastname: Suzuki
authors.forename: Kazuhiro
authors.initials: K
authors.lastname: Sugihara
authors.forename: Naohiro
authors.initials: N
authors.lastname: Kanayama
authors.forename: Mitsuo
authors.initials: M
authors.lastname: Hiramatsu
mesh_terms: D000650:Amnion / Q000254:growth & development / Q000293:injuries / Q000473:pathology; D000653:Amniotic Fluid / Q000737:chemistry / Q000502:physiology; D000818:Animals; D002478:Cells, Cultured; D002626:Chemistry, Pharmaceutical; D004195:Disease Models, Animal; D015536:Down-Regulation; D004357:Drug Synergism; D006801:Humans; D008070:Lipopolysaccharides / Q000008:administration & dosage; D008274:Magnesium / Q000008:administration & dosage / Q000494:pharmacology*; D008297:Male; D009504:Neutrophils / Q000187:drug effects* / Q000378:metabolism / Q000473:pathology; D018384:Oxidative Stress / Q000187:drug effects; D010538:Peritonitis / Q000139:chemically induced / Q000188:drug therapy / Q000276:immunology* / Q000473:pathology; D051381:Rats; D013481:Superoxides / Q000378:metabolism*; D015032:Zinc / Q000008:administration & dosage / Q000494:pharmacology*
chemical_list: D008070:Lipopolysaccharides; D013481:Superoxides; D008274:Magnesium; D015032:Zinc