title: Metanx alleviates multiple manifestations of peripheral neuropathy and increases intraepidermal nerve fiber density in Zucker diabetic fatty rats.
abstract: Metanx is a product containing L-methylfolate, pyridoxal 5'-phosphate, and methylcobalamin for management of endothelial dysfunction. Metanx ingredients counteract endothelial nitric oxide synthase uncoupling and oxidative stress in vascular endothelium and peripheral nerve. This study evaluates Metanx on diabetic peripheral neuropathy in ZDF rats, a model of type 2 diabetes. Metanx was administered to 15-week-old ZDF and ZDF lean rats at either 4.87 mg ⋅ kg(-1) ⋅ day(-1) (a body weight-based equivalent of human dose) or 24.35 mg ⋅ kg(-1) ⋅ day(-1) by oral gavage two times a day for 4 weeks. Both doses alleviated hind limb digital sensory, but not sciatic motor, nerve conduction slowing and thermal and mechanical hypoalgesia in the absence of any reduction of hyperglycemia. Low-dose Metanx increased intraepidermal nerve fiber density but did not prevent morphometric changes in distal tibial nerve myelinated fibers. Metanx treatment counteracted endothelial nitric oxide synthase uncoupling, inducible nitric oxide synthase upregulation, and methylglyoxal-derived advanced glycation end product, nitrotyrosine, and nitrite/nitrate accumulation in the peripheral nerve. In conclusion, Metanx, at a body weight-based equivalent of human dose, increased intraepidermal nerve fiber density and improved multiple parameters of peripheral nerve function in ZDF rats. Clinical studies are needed to determine if Metanx finds use in management of diabetic peripheral neuropathy.
authors: Pennington Biomedical Research Center, Louisiana State University System, Baton Rouge, Louisiana, USA.
authors: Hanna
authors: H
authors: Shevalye
authors: Pierre
authors: P
authors: Watcho
authors: Roman
authors: R
authors: Stavniichuk
authors: Elena
authors: E
authors: Dyukova
authors: Sergey
authors: S
authors: Lupachyk
authors: Irina G
authors: IG
authors: Obrosova
mesh_terms: D000818:Animals; D003924:Diabetes Mellitus, Type 2 / Q000188:drug therapy* / Q000503:physiopathology; D003929:Diabetic Neuropathies / Q000188:drug therapy*; D004195:Disease Models, Animal; D005492:Folic Acid / Q000031:analogs & derivatives* / Q000627:therapeutic use; D006930:Hyperalgesia / Q000188:drug therapy; D008297:Male; D009412:Nerve Fibers / Q000187:drug effects*; D009431:Neural Conduction / Q000187:drug effects / Q000502:physiology; D052247:Nitric Oxide Synthase Type II / Q000378:metabolism; D052250:Nitric Oxide Synthase Type III / Q000378:metabolism; D011732:Pyridoxal Phosphate / Q000627:therapeutic use*; D051381:Rats; D011924:Rats, Zucker; D012584:Sciatic Nerve / Q000187:drug effects / Q000503:physiopathology; D013979:Tibial Nerve / Q000187:drug effects / Q000503:physiopathology; D014443:Tyrosine / Q000031:analogs & derivatives / Q000378:metabolism; D014805:Vitamin B 12 / Q000031:analogs & derivatives* / Q000627:therapeutic use
chemical_list: C575384:metanx; C002744:3-nitrotyrosine; D014443:Tyrosine; D011732:Pyridoxal Phosphate; D005492:Folic Acid; D052247:Nitric Oxide Synthase Type II; D052250:Nitric Oxide Synthase Type III; C496318:Nos2 protein, rat; C496316:Nos3 protein, rat; D014805:Vitamin B 12