title: Preclinical assessment of β-d-mannuronic acid (M2000) as a non-steroidal anti-inflammatory drug.
abstract: BACKGROUND
  β-d-Mannuronic acid (M2000) has shown its therapeutic effects with the greatest tolerability and efficacy in various experimental models such as experimental autoimmune encephalomyelitis (EAE), adjuvant induced arthritis (AIA), nephrotic syndrome, and acute glomerulonephritis. Despite pharmacological effects of β-D-mannuronic acid, there have been no systematic toxicological studies on its safety so far.
  
  
  OBJECTIVE
  The study was designed to determine the acute and subchronic toxicity of β-D-mannuronic acid, an anti-inflammatory agent, in healthy male NMRI mice and Wistar rats, respectively.
  
  
  METHODS
  For the acute toxicity study, the animals received orally five different single doses of β-D-mannuronic acid and were kept under observation for 14 d. In the subchronic study, 24 Wistar male rats were divided into four groups and were treated orally (gavage) once daily with test substance preparation at dose levels of 0, 50, 250, and 1250 mg/kg body weight for at least 63 consecutive days (9 weeks). Mortality, clinical signs, body weight changes, hematological and biochemical parameters, gross findings, organ weights, and histopathological determinations were monitored during the study.
  
  
  RESULTS
  The results of acute toxicity indicated that the LD50 of β-D-mannuronic acid is 4.6 g/kg. We found no mortality and no abnormality in clinical signs, body weight, relative organ weights, or necropsy in any of the animals in the subchronic study. Additionally, the results showed no significant difference in hematological, biochemical, and histopathological parameters in rats.
  
  
  CONCLUSIONS
  Our results suggest that β-D-mannuronic acid is relatively safe when administered orally in animals.
authors.affiliation: a Department of Immunology , School of Public Health, Tehran University of Medical Sciences , Tehran , Iran .
authors.forename: Mohammad Javad
authors.initials: MJ
authors.lastname: Fattahi
authors.affiliation: b Department of Toxicology and Pharmacology , Faculty of Pharmacy and Pharmaceutical Sciences Research Center, Tehran University of Medical Sciences , Tehran , Iran .
authors.forename: Mohammad
authors.initials: M
authors.lastname: Abdollahi
authors.affiliation: c Research Center for Immunodeficiencies, Children's Medical Center, Tehran University of Medical Sciences , Tehran , Iran .
authors.forename: Asghar
authors.initials: A
authors.lastname: Agha Mohammadi
authors.affiliation: d Center for Air Pollution Research (CAPR), Institute for Environmental Research (IER), Tehran University of Medical Sciences , Tehran , Iran .
authors.forename: Noushin
authors.initials: N
authors.lastname: Rastkari
authors.affiliation: b Department of Toxicology and Pharmacology , Faculty of Pharmacy and Pharmaceutical Sciences Research Center, Tehran University of Medical Sciences , Tehran , Iran .
authors.forename: Reza
authors.initials: R
authors.lastname: Khorasani
authors.affiliation: a Department of Immunology , School of Public Health, Tehran University of Medical Sciences , Tehran , Iran .
authors.forename: Hossein
authors.initials: H
authors.lastname: Ahmadi
authors.affiliation: a Department of Immunology , School of Public Health, Tehran University of Medical Sciences , Tehran , Iran .
authors.forename: Farzaneh
authors.initials: F
authors.lastname: Tofighi Zavareh
authors.affiliation: e Department of Anatomy and Pathology , Faculty of Medicine, Shahed University , Tehran , Iran , and.
authors.forename: Reza
authors.initials: R
authors.lastname: Sedaghat
authors.affiliation: f Department of Cellular and Molecular Biology , Kish International Campus, University of Tehran , Tehran , Iran.
authors.forename: Nakisa
authors.initials: N
authors.lastname: Tabrizian
authors.affiliation: a Department of Immunology , School of Public Health, Tehran University of Medical Sciences , Tehran , Iran .
authors.forename: Abbas
authors.initials: A
authors.lastname: Mirshafiey
mesh_terms: D000818:Animals; D000894:Anti-Inflammatory Agents, Non-Steroidal / Q000633:toxicity*; D004305:Dose-Response Relationship, Drug; D004353:Drug Evaluation, Preclinical / Q000379:methods; D006603:Hexuronic Acids / Q000633:toxicity*; D008297:Male; D051379:Mice; D051381:Rats; D017208:Rats, Wistar; D023382:Toxicity Tests, Acute / Q000379:methods*; D059550:Toxicity Tests, Subchronic / Q000379:methods*
chemical_list: D000894:Anti-Inflammatory Agents, Non-Steroidal; D006603:Hexuronic Acids; C008324:mannuronic acid
keywords: Acute toxicity; M2000; non-steroidal anti-inflammatory drugs; subchronic toxicity; β-D-mannuronic acid