Preclinical and pharmacotoxicology evaluation of α-l-guluronic acid (G2013) as a non-steroidal anti-inflammatory drug with immunomodulatory property.
BACKGROUND
Therapeutic effects of α-l-guluronic acid with the greatest tolerability and efficacy (G2013) have been shown in experimental model of multiple sclerosis and other in vitro and in vivo examinations regarding α-l-guluronic acid; there are no toxicological researches on its safety although the pharmacological impacts have been recorded.


OBJECTIVE
This study was designed to determine the acute and sub chronic toxicity of α-l-guluronic acid in healthy male and female BALB/c mice.


METHODS
For the acute toxicity study, the animals orally received five different single doses of α-l-guluronic acid and were kept under observation for 14 d. In the sub-chronic study, 24 male and female BALB/c mice were divided into four groups and treated daily with test substance preparation at dose levels of 0, 50, 250, and 1250 mg/kg body weight for at least 90 consecutive days. The mortality, body weight changes, clinical signs, hematological and biochemical parameters, gross findings, histopathological, and organs weight determinants were monitored during this study.


RESULTS
The results of acute toxicity indicated that the LD50 of α-l-guluronic acid is 4.8 g/kg. We found no mortality or abnormality in clinical signs, body weight, relative organs weight, 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 α-l-guluronic acid has high safety when administered orally in animals.
a Department of Immunology, School of Public Health , Tehran University of Medical Science , Tehran , Iran.
Sepideh
S
Nazeri
a Department of Immunology, School of Public Health , Tehran University of Medical Science , Tehran , Iran.
Shahin
S
Khadem Azarian
a Department of Immunology, School of Public Health , Tehran University of Medical Science , Tehran , Iran.|b Shiraz Institute for Cancer Research, School of Medicine , Shiraz University of Medical Science , Shiraz , Iran.
Mohammad Javad
MJ
Fattahi
c Department of Anatomy and Pathology, Faculty of medicine , Shahed University , Tehran , Iran.
Reza
R
Sedaghat
a Department of Immunology, School of Public Health , Tehran University of Medical Science , Tehran , Iran.
Farzaneh
F
Tofighi Zavareh
a Department of Immunology, School of Public Health , Tehran University of Medical Science , Tehran , Iran.
Zahra
Z
Aghazadeh
d Department of Toxicology, School of Pharmacy , Tehran University of Medical Science , Tehran , Iran.|e Toxicology and Diseases Group, Pharmaceutical Sciences Research Group , Tehran University of Medical Science , Tehran , Iran.
Mohammad
M
Abdollahi
a Department of Immunology, School of Public Health , Tehran University of Medical Science , Tehran , Iran.
Abbas
A
Mirshafiey
D000818:Animals; D000893:Anti-Inflammatory Agents / Q000009:adverse effects / Q000493:pharmacokinetics / Q000494:pharmacology; D004195:Disease Models, Animal; D004353:Drug Evaluation, Preclinical; D005260:Female; D020723:Glucuronic Acid / Q000009:adverse effects / Q000276:immunology / Q000493:pharmacokinetics / Q000494:pharmacology; D006603:Hexuronic Acids; D007155:Immunologic Factors / Q000009:adverse effects / Q000276:immunology / Q000493:pharmacokinetics / Q000494:pharmacology; D008297:Male; D051379:Mice; D008807:Mice, Inbred BALB C; D009103:Multiple Sclerosis / Q000188:drug therapy* / Q000276:immunology / Q000473:pathology; D051381:Rats; D014574:Uronic Acids / Q000009:adverse effects / Q000276:immunology / Q000493:pharmacokinetics / Q000494:pharmacology
D000893:Anti-Inflammatory Agents; D006603:Hexuronic Acids; D007155:Immunologic Factors; D014574:Uronic Acids; C007896:guluronic acid; D020723:Glucuronic Acid
acute; anti-inflammatory; immunomodulatory; subchronic; α-l-Guluronic acid