title: Toxicological evaluation of RGTA OTR4120, a heparan sulfate mimetic.
abstract: Heparan sulfate mimetic polymers promotes tissue repair when injected locally in doses of 1-2mg/kg by various routes. These biopolymers, have been extensively studied for their diverse biological activities. However, there is no detailed report investigating the toxicity of OTR4120. In this study, the acute and subchronic (30 days) toxicity of varying levels of OTR4120 was investigated in mice after intraperitoneal administration. The results showed that no significant toxicological changes were observed when 50mg/kg body weight per day OTR4120 was administered to mice. But when the dose was increased to 60 and 70 mg/kg body weight per day, the clotting time was significantly prolonged. Alanine aminotransferase (ALT), aspartate aminotransferase (AST) and alkaline phosphatase (ALP) activities were reduced female and male at dose 70 mg/kg body weight per day. These blood biochemistry data suggest that OTR4120 have a hepatoprotective effect. Based on these results, it can be concluded that the no adverse effect level of OTR4120 is 50 mg/kg body weight per day.
authors.affiliation: Laboratoire CRRET/CNRS UMR 7149, Université Paris 12 val de Marne, PRES Paris Est, 61, Avenue du Général de Gaulle 94010, Créteil Cedex, France. charef@univ-paris12.fr
authors.forename: Said
authors.initials: S
authors.lastname: Charef
authors.forename: Michel
authors.initials: M
authors.lastname: Tulliez
authors.forename: Liliane
authors.initials: L
authors.lastname: Esmilaire
authors.forename: José
authors.initials: J
authors.lastname: Courty
authors.forename: Dulce
authors.initials: D
authors.lastname: Papy-Garcia
mesh_terms: D000818:Animals; D032701:Biomimetics; D001772:Blood Cell Count; D001777:Blood Coagulation / Q000187:drug effects; D001835:Body Weight / Q000187:drug effects; D004305:Dose-Response Relationship, Drug; D004798:Enzymes / Q000097:blood; D005260:Female; D006025:Glycosaminoglycans / Q000138:chemical synthesis / Q000737:chemistry / Q000633:toxicity*; D006497:Heparan Sulfate / Q000737:chemistry*; D007274:Injections, Intraperitoneal; D008297:Male; D051379:Mice; D009929:Organ Size / Q000187:drug effects
chemical_list: D004798:Enzymes; D006025:Glycosaminoglycans; D006497:Heparan Sulfate; C533322:OTR4120