Metanx Alleviates Multiple Manifestations of Peripheral Neuropathy and Increases Intraepidermal Nerve Fiber Density in Zucker Diabetic Fatty Rats

Pennington Biomedical Research Center, Louisiana State University System, Baton Rouge, Louisiana, USA.
Diabetes (Impact Factor: 8.1). 06/2012; 61(8):2126-33. DOI: 10.2337/db11-1524
Source: PubMed


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.

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Available from: Sergey Lupachyk
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    • "Uncoupling of eNOS is the underlying mechanism of endothelial dysfunction associated with cardiovascular conditions such as hypertension, stroke, and heart failure [21,22]. Recently, eNOS uncoupling was shown to participate in endothelial dysfunction in diabetic mice [23] and to mediate peripheral neuropathy in diabetic rats [24]. In Zucker diabetic fatty rats, endothelial dysfunction and decreased NO availability were attributed to dissociation of eNOS from HSP90, an effect elicited by increased calpain activity [25]. "
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    • "Tactile responses were evaluated by quantifying the withdrawal threshold of the hindpaw in response to stimulation with flexible von Frey filaments . We described those methods in detail in our previous publications (Drel et al., 2007; Obrosova et al., 2007; Shevalye et al., 2012b). "
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