title: Hepatic and intestine alterations in mice after prolonged exposure to low oral doses of Microcystin-LR.
abstract: Oral intake of Microcystin-LR (MC-LR) is the principal route of exposure to this toxin, with prolonged exposure leading to liver damage of unspecific symptomatology. The aim of the present paper was therefore to investigate the liver and intestine damage generated by prolonged oral exposure to low MC-LR doses (50 and 100 μg MC-LR/kg body weight, administrated every 48 h during a month) in a murine model. We found alterations in TBARS, SOD activity and glutathione content in liver and intestine of mice exposed to both doses of MC-LR. Furthermore, the presence of MC-LR was detected in both organs. We also found hepatic steatosis (3.6 ± 0.6% and 15.3 ± 1.6%) and a decrease in intraepithelial lymphocytes (28.7 ± 5.0% and 44.2 ± 8.7%) in intestine of 50- and 100-μg MC-LR/kg treated animals, respectively. This result could have important implications for mucosal immunity, since intraepithelial lymphocytes are the principal effectors of this system. Our results indicate that prolonged oral exposure at 50 μg MC-LR/kg every 48 h generates significant damage not only in liver but also in intestine. This finding calls for a re-appraisal of the currently accepted NOAEL (No Observed Adverse Effect Level), 40 μg MC-LR/kg body weight, used to derive the guideline value for MC-LR in drinking water.
authors.affiliation: Área de Toxicología, Facultad de Ciencias Exactas, Universidad Nacional de La Plata (UNLP-CONICET), La Plata, Argentina. Electronic address: danielasedan@yahoo.com.ar.
authors.forename: Daniela
authors.initials: D
authors.lastname: Sedan
authors.affiliation: Cátedra de Patología B, Facultad de Ciencias Médicas, Universidad Nacional de La Plata, La Plata, Argentina. Electronic address: martinlaguens@hotmail.com.
authors.forename: Martín
authors.initials: M
authors.lastname: Laguens
authors.affiliation: Área de Toxicología, Facultad de Ciencias Exactas, Universidad Nacional de La Plata (UNLP-CONICET), La Plata, Argentina. Electronic address: guido17lb@gmail.com.
authors.forename: Guido
authors.initials: G
authors.lastname: Copparoni
authors.affiliation: Área de Toxicología, Facultad de Ciencias Exactas, Universidad Nacional de La Plata (UNLP-CONICET), La Plata, Argentina. Electronic address: joam7914@gmail.com.
authors.forename: Jorge Oswaldo
authors.initials: JO
authors.lastname: Aranda
authors.affiliation: Área de Toxicología, Facultad de Ciencias Exactas, Universidad Nacional de La Plata (UNLP-CONICET), La Plata, Argentina; Centro de Investigación y Desarrollo en Criotecnología de Alimentos (CIDCA-CONICET), La Plata, Argentina. Electronic address: leda@biol.unlp.edu.ar.
authors.forename: Leda
authors.initials: L
authors.lastname: Giannuzzi
authors.affiliation: INIBIOLP (Instituto de Investigaciones Bioquímicas de La Plata), Cátedra de Bioquímica y Biología Molecular, Facultad de Ciencias Médicas, Universidad Nacional de La Plata, La Plata, Argentina. Electronic address: contactocarlos@hotmail.com.
authors.forename: Carlos Alberto
authors.initials: CA
authors.lastname: Marra
authors.affiliation: Área de Toxicología, Facultad de Ciencias Exactas, Universidad Nacional de La Plata (UNLP-CONICET), La Plata, Argentina. Electronic address: dandrinolo@yahoo.com.
authors.forename: Darío
authors.initials: D
authors.lastname: Andrinolo
mesh_terms: D000284:Administration, Oral; D000818:Animals; D015415:Biomarkers / Q000378:metabolism; D004305:Dose-Response Relationship, Drug; D005234:Fatty Liver / Q000139:chemically induced / Q000473:pathology; D005978:Glutathione / Q000378:metabolism; D007422:Intestines / Q000187:drug effects* / Q000473:pathology; D015227:Lipid Peroxidation / Q000187:drug effects; D008099:Liver / Q000187:drug effects* / Q000473:pathology; D008214:Lymphocytes / Q000187:drug effects / Q000378:metabolism; D008297:Male; D008315:Malondialdehyde / Q000378:metabolism; D008387:Marine Toxins; D051379:Mice; D052998:Microcystins / Q000633:toxicity*; D019055:No-Observed-Adverse-Effect Level; D018384:Oxidative Stress / Q000187:drug effects; D017392:Thiobarbituric Acid Reactive Substances / Q000378:metabolism
chemical_list: D015415:Biomarkers; D008387:Marine Toxins; D052998:Microcystins; D017392:Thiobarbituric Acid Reactive Substances; D008315:Malondialdehyde; C057862:cyanoginosin LR; D005978:Glutathione
keywords: Intraepithelial lymphocytes; Microcystin-LR; Oral exposure; Prolonged intoxication