title: Melatonin reduces lead levels in blood, brain and bone and increases lead excretion in rats subjected to subacute lead treatment.
abstract: Melatonin, a hormone known for its effects on free radical scavenging and antioxidant activity, can reduce lead toxicity in vivo and in vitro.We examined the effects of melatonin on lead bio-distribution. Rats were intraperitoneally injected with lead acetate (10, 15 or 20mg/kg/day) with or without melatonin (10mg/kg/day) daily for 10 days. In rats intoxicated with the highest lead doses, those treated with melatonin had lower lead levels in blood and higher levels in urine and feces than those treated with lead alone, suggesting that melatonin increases lead excretion. To explore the mechanism underlying this effect, we first assessed whether lead/melatonin complexes were formed directly. Electronic density functional (DFT) calculations showed that a lead/melatonin complex is energetically feasible; however, UV spectroscopy and NMR analysis showed no evidence of such complexes. Next, we examined the liver mRNA levels of metallothioneins (MT) 1 and 2. Melatonin cotreatment increased the MT2 mRNA expression in the liver of rats that received the highest doses of lead. The potential effects of MTs on the tissue distribution and excretion of lead are not well understood. This is the first report to suggest that melatonin directly affects lead levels in organisms exposed to subacute lead intoxication.
authors.affiliation: Universidad de Guanajuato, Departamento de Farmacia, México.
authors.forename: Everardo
authors.initials: E
authors.lastname: Hernández-Plata
authors.affiliation: Universidad de Guanajuato, Departamento de Farmacia, México.
authors.forename: Fátima
authors.initials: F
authors.lastname: Quiroz-Compeán
authors.affiliation: Universidad de Guanajuato, Departamento de Farmacia, México.
authors.forename: Gonzalo
authors.initials: G
authors.lastname: Ramírez-Garcia
authors.affiliation: Universidad de Guanajuato, Departamento de Química, México.
authors.forename: Eunice Yáñez
authors.initials: EY
authors.lastname: Barrientos
authors.affiliation: Universidad de Guanajuato, Departamento de Farmacia, México.
authors.forename: Nadia M
authors.initials: NM
authors.lastname: Rodríguez-Morales
authors.affiliation: Universidad de Guanajuato, y Departamento de Biología, México.
authors.forename: Alberto
authors.initials: A
authors.lastname: Flores
authors.affiliation: Universidad de Guanajuato, Departamento de Química, México.
authors.forename: Katarzina
authors.initials: K
authors.lastname: Wrobel
authors.affiliation: Universidad de Guanajuato, Departamento de Química, México.
authors.forename: Kazimierz
authors.initials: K
authors.lastname: Wrobel
authors.affiliation: Instituto de Neurobiología UNAM, Campus Juriquilla, Querétaro, México.
authors.forename: Isabel
authors.initials: I
authors.lastname: Méndez
authors.affiliation: Instituto de Neurobiología UNAM, Campus Juriquilla, Querétaro, México.
authors.forename: Mauricio
authors.initials: M
authors.lastname: Díaz-Muñoz
authors.affiliation: Universidad de Guanajuato, Departamento de Farmacia, México.
authors.forename: Juvencio
authors.initials: J
authors.lastname: Robles
authors.affiliation: Universidad de Guanajuato, Departamento de Farmacia, México. Electronic address: alfarom@ugto.mx.
authors.forename: Minerva
authors.initials: M
authors.lastname: Martínez-Alfaro
mesh_terms: D000818:Animals; D001842:Bone and Bones / Q000187:drug effects / Q000378:metabolism*; D001921:Brain / Q000187:drug effects / Q000378:metabolism*; D016166:Free Radical Scavengers / Q000494:pharmacology*; D007668:Kidney / Q000187:drug effects / Q000378:metabolism; D007854:Lead / Q000097:blood / Q000378:metabolism* / Q000652:urine; D008099:Liver / Q000187:drug effects / Q000378:metabolism; D008297:Male; D008550:Melatonin / Q000494:pharmacology*; D008668:Metallothionein / Q000378:metabolism; D051381:Rats; D017208:Rats, Wistar; D014018:Tissue Distribution
chemical_list: D016166:Free Radical Scavengers; D007854:Lead; D008668:Metallothionein; D008550:Melatonin
keywords: Lead acetate; Melatonin; Metallothioneins; Reduction