title: Evidence for oral agmatine sulfate safety--a 95-day high dosage pilot study with rats.
abstract: Agmatine, decarboxylated arginine, exerts beneficial effects in various experimental disease models. Clinical trials indicate the safety and effectiveness of short-term (up to 21 days) high dose regimens of oral agmatine sulfate, but longer term studies are lacking. This pilot study undertook to assess the safety of a longer term high dosage oral agmatine sulfate in laboratory rats. Adult Wistar rats consumed 5.3 g/l agmatine sulfate in their drinking water for 95 days, a regimen estimated to result in a daily dosage of absorbed agmatine of about 100mg/kg. Animals' body weight, water consumption and blood pressure were periodically measured, and general cage behavior, fur appearance, urination and feces appearance monitored. These parameters were also determined at 20 days after treatment cessation (day 115). On days 95 and 115, animals were euthanized for gross necropsy assessment. Agmatine-treated rats showed slight, but significant reductions in body weight and blood pressure, and reduced water consumption during treatment, which recovered completely within 20 days after treatment cessation. Otherwise, no abnormal behaviors or organ pathologies were observed. These findings are first to suggest apparent safety of sub-chronic high dosage dietary agmatine sulfate in laboratory rats, thus lending further support to the therapeutic applications of agmatine.
authors.affiliation: Department of Physiology and Pharmacology, Sackler Faculty of Medicine, Tel Aviv University, Tel Aviv, Israel; Laboratory of Neuroscience, Research and Development, Assaf Harofeh Medical Center, Zrifin, Israel. Electronic address: gmgilad@gmail.com.
authors.forename: Gad M
authors.initials: GM
authors.lastname: Gilad
authors.forename: Varda H
authors.initials: VH
authors.lastname: Gilad
mesh_terms: D000284:Administration, Oral; D000376:Agmatine / Q000008:administration & dosage / Q000009:adverse effects* / Q000031:analogs & derivatives*; D000818:Animals; D001522:Behavior, Animal / Q000187:drug effects; D001794:Blood Pressure / Q000187:drug effects; D001835:Body Weight / Q000187:drug effects; D004305:Dose-Response Relationship, Drug; D004326:Drinking / Q000187:drug effects; D005260:Female; D008297:Male; D010865:Pilot Projects; D051381:Rats; D017208:Rats, Wistar; D059550:Toxicity Tests, Subchronic
chemical_list: D000376:Agmatine
keywords: AGE; Agmatine treatment; Blood pressure; Dietary ingredients; GABA; GI; MMPs; NO; Neuroprotection; SBP; Wistar rats; advanced glycation end product; gastrointestinal; matrix metalloproteases; nitric oxide; systolic blood pressure; γ-aminobutyric acid