title: Effect of tempol on peripheral neuropathy in diet-induced obese and high-fat fed/low-dose streptozotocin-treated C57Bl6/J mice.
abstract: In this study, we sought to determine the efficacy of tempol on multiple neuropathic endpoints in a diet-induced obese mouse, a model of pre-diabetes, and a high-fat fed low-dose streptozotocin treated mouse, a model of type 2 diabetes. Tempol (4-hydroxy-2,2,6,6-tetramethylpiperdine -1-oxyl) is a low molecular weight, water soluble, membrane permeable, and metal-independent superoxide dismutase mimetic that has been widely used in cellular studies for the removal of intracellular and extracellular superoxide. This in vivo study was designed to be an early intervention. Fourteen weeks post-high-fat diet (6 weeks post-hyperglycemia) control, obese, and diabetic mice were divided into no treatment and treatment groups. The treated mice received tempol by gavage (150 mg/kg in water), while the untreated mice received vehicle. The diet-induced obese and the diabetic mice were maintained on the high-fat diet for the duration of the study, while the control group was maintained on the standard diet. Obesity and diabetes caused slowing of motor and sensory nerve conduction, reduction in intraepidermal nerve fiber density, thermal hypoalgesia, and mechanical allodynia. Treatment with tempol partially or completely protected obese and diabetic mice from these deficits. These studies suggest that tempol or other effective scavengers of reactive oxygen species may be a viable option for treating neural complications associated with obesity or type 2 diabetes.
authors.affiliation: a Department of Internal Medicine , University of Iowa , Iowa City , IA , USA.
authors.forename: Alexander
authors.initials: A
authors.lastname: Obrosov
authors.affiliation: a Department of Internal Medicine , University of Iowa , Iowa City , IA , USA.
authors.forename: Hanna
authors.initials: H
authors.lastname: Shevalye
authors.affiliation: a Department of Internal Medicine , University of Iowa , Iowa City , IA , USA.
authors.forename: Lawrence J
authors.initials: LJ
authors.lastname: Coppey
authors.affiliation: a Department of Internal Medicine , University of Iowa , Iowa City , IA , USA.|b Department of Veterans Affairs Iowa City Health Care System , Iowa City , IA , USA.|c Fraternal Order of Eagles Diabetes Research Center, University of Iowa , Iowa City , IA , USA.
authors.forename: Mark A
authors.initials: MA
authors.lastname: Yorek
mesh_terms: D000818:Animals; D003497:Cyclic N-Oxides / Q000008:administration & dosage / Q000494:pharmacology*; D003921:Diabetes Mellitus, Experimental / Q000139:chemically induced / Q000150:complications*; D003924:Diabetes Mellitus, Type 2 / Q000139:chemically induced / Q000150:complications*; D059305:Diet, High-Fat / Q000009:adverse effects*; D004195:Disease Models, Animal; D051379:Mice; D008810:Mice, Inbred C57BL; D009765:Obesity / Q000150:complications*; D010523:Peripheral Nervous System Diseases / Q000150:complications* / Q000188:drug therapy*; D013113:Spin Labels; D013311:Streptozocin
chemical_list: D003497:Cyclic N-Oxides; D013113:Spin Labels; D013311:Streptozocin; C001803:tempol
keywords: Tempol; diabetes; diabetic neuropathy; sensory nerve fibers