Tadalafil Promotes the Recovery of Peripheral Neuropathy in Type II Diabetic MiceReport as inadecuate




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We previously demonstrated that treatment of diabetic peripheral neuropathy with the short 4 hours half-life phosphodiesterase 5 PDE5 inhibitor, sildenafil, improved functional outcome in diabetic db-db mice. To further examine the effect of PDE5 inhibition on diabetic peripheral neuropathy, we investigated the effect of another potent PDE5 inhibitor, tadalafil, on diabetic peripheral neuropathy. Tadalafil is pharmacokinetically distinct from sildenafil and has a longer half-life 17+hours than sildenafil. Diabetic mice BKS.Cg-m+-+Leprdb-J, db-db at age 20 weeks were treated with tadalafil every 48 hours for 8 consecutive weeks. Compared with diabetic mice treated with saline, tadalafil treatment significantly improved motor and sensory conduction velocities in the sciatic nerve and peripheral thermal sensitivity. Tadalafil treatment also markedly increased local blood flow and the density of FITC-dextran perfused vessels in the sciatic nerve concomitantly with increased intraepidermal nerve fiber density. Moreover, tadalafil reversed the diabetes-induced reductions of axon diameter and myelin thickness and reversed the diabetes-induced increased g-ratio in the sciatic nerve. Furthermore, tadalafil enhanced diabetes-reduced nerve growth factor NGF and platelet-derived growth factor-C PDGF-C protein levels in diabetic sciatic nerve tissue. The present study demonstrates that tadalafil increases regional blood flow in the sciatic nerve tissue, which may contribute to the improvement of peripheral nerve function and the amelioration of diabetic peripheral neuropathy.



Author: Lei Wang , Michael Chopp, Alexandra Szalad, XueRong Lu, LongFei Jia, Mei Lu, Rui Lan Zhang, Zheng Gang Zhang

Source: http://plos.srce.hr/



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