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Preclinical Assessment of Β - D -Mannuronic Acid (M2000) As a Non-Steroidal Anti-Inflammatory Drug Publisher Pubmed



Fattahi MJ1 ; Abdollahi M2 ; Agha Mohammadi A3 ; Rastkari N4 ; Khorasani R2 ; Ahmadi H1 ; Tofighi Zavareh F1 ; Sedaghat R5 ; Tabrizian N6 ; Mirshafiey A1
Authors
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Authors Affiliations
  1. 1. Department of Immunology, School of Public Health, Tehran University of Medical Sciences, Tehran, Iran
  2. 2. Department of Toxicology and Pharmacology, Faculty of Pharmacy and Pharmaceutical Sciences Research Center, Tehran University of Medical Sciences, Tehran, Iran
  3. 3. Research Center for Immunodeficiencies, Childrens Medical Center, Tehran University of Medical Sciences, Tehran, Iran
  4. 4. Center for Air Pollution Research (CAPR), Institute for Environmental Research (IER), Tehran University of Medical Sciences, Tehran, Iran
  5. 5. Department of Anatomy and Pathology, Faculty of Medicine, Shahed University, Tehran, Iran
  6. 6. Department of Cellular and Molecular Biology, Kish International Campus, University of Tehran, Tehran, Iran

Source: Immunopharmacology and Immunotoxicology Published:2015


Abstract

Context: 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.Materials and 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. © 2015 Taylor & Francis.
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