title: Tadalafil Promotes the Recovery of Peripheral Neuropathy in Type II Diabetic Mice.
abstract: 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.
authors.affiliation: Department of Neurology, Henry Ford Hospital, 2799 W. Grand Boulevard, Detroit, Michigan, 48202, United States of America.
authors.forename: Lei
authors.initials: L
authors.lastname: Wang
authors.affiliation: Department of Neurology, Henry Ford Hospital, 2799 W. Grand Boulevard, Detroit, Michigan, 48202, United States of America.|Department of Physics, Oakland University, Rochester, Michigan, 48309, United States of America.
authors.forename: Michael
authors.initials: M
authors.lastname: Chopp
authors.affiliation: Department of Neurology, Henry Ford Hospital, 2799 W. Grand Boulevard, Detroit, Michigan, 48202, United States of America.
authors.forename: Alexandra
authors.initials: A
authors.lastname: Szalad
authors.affiliation: Department of Neurology, Henry Ford Hospital, 2799 W. Grand Boulevard, Detroit, Michigan, 48202, United States of America.
authors.forename: XueRong
authors.initials: X
authors.lastname: Lu
authors.affiliation: Department of Neurology, Henry Ford Hospital, 2799 W. Grand Boulevard, Detroit, Michigan, 48202, United States of America.
authors.forename: LongFei
authors.initials: L
authors.lastname: Jia
authors.affiliation: Department of Neurology, Henry Ford Hospital, 2799 W. Grand Boulevard, Detroit, Michigan, 48202, United States of America.
authors.forename: Mei
authors.initials: M
authors.lastname: Lu
authors.affiliation: Department of Neurology, Henry Ford Hospital, 2799 W. Grand Boulevard, Detroit, Michigan, 48202, United States of America.
authors.forename: Rui Lan
authors.initials: RL
authors.lastname: Zhang
authors.affiliation: Department of Neurology, Henry Ford Hospital, 2799 W. Grand Boulevard, Detroit, Michigan, 48202, United States of America.
authors.forename: Zheng Gang
authors.initials: ZG
authors.lastname: Zhang
mesh_terms: D000818:Animals; D001786:Blood Glucose; D003921:Diabetes Mellitus, Experimental / Q000188:drug therapy / Q000503:physiopathology; D003924:Diabetes Mellitus, Type 2 / Q000188:drug therapy* / Q000235:genetics / Q000503:physiopathology; D003929:Diabetic Neuropathies; D004195:Disease Models, Animal; D005786:Gene Expression Regulation / Q000187:drug effects; D006801:Humans; D008222:Lymphokines / Q000096:biosynthesis / Q000235:genetics; D051379:Mice; D016688:Mice, Inbred NOD / Q000235:genetics; D009043:Motor Activity / Q000187:drug effects; D009412:Nerve Fibers / Q000187:drug effects / Q000473:pathology; D020932:Nerve Growth Factor / Q000096:biosynthesis / Q000235:genetics; D010523:Peripheral Nervous System Diseases / Q000188:drug therapy* / Q000235:genetics / Q000503:physiopathology; D010982:Platelet-Derived Growth Factor / Q000096:biosynthesis / Q000235:genetics; D012584:Sciatic Nerve / Q000098:blood supply / Q000187:drug effects* / Q000503:physiopathology; D000068581:Tadalafil / Q000008:administration & dosage*
chemical_list: D001786:Blood Glucose; D008222:Lymphokines; D010982:Platelet-Derived Growth Factor; C411423:platelet-derived growth factor C; D000068581:Tadalafil; D020932:Nerve Growth Factor