Preclinical assessment of β-D-mannuronic acid (M2000) as a non-steroidal anti-inflammatory drug

Context: -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 -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 -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 -D-mannuronic acid and were kept under observation for 14d. 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 1250mg/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 -D-mannuronic acid is 4.6g/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 -D-mannuronic acid is relatively safe when administered orally in animals.