Journal article
Early vs. late intervention of high fat/low dose streptozotocin treated C57Bl/6J mice with enalapril, α-lipoic acid, menhaden oil or their combination: Effect on diabetic neuropathy related endpoints
Neuropharmacology, Vol.116, pp.122-131
04/2017
DOI: 10.1016/j.neuropharm.2016.12.022
PMCID: PMC5385152
PMID: 28025096
Abstract
We have previously demonstrated that enalapril, α-lipoic acid and menhaden (fish) oil has potential as a treatment for diabetic peripheral neuropathy. In this study we sought to determine the efficacy of these treatments individually or in combination on multiple neuropathic endpoints in a high fat fed low dose streptozotocin treated mouse, a model of type 2 diabetes, following early or late intervention. Four or twelve weeks after the onset of hyperglycemia, diabetic mice were treated with enalapril, α-lipoic acid, menhaden oil or their combination for 12 weeks. Afterwards, endpoints including glucose tolerance, motor and sensory nerve conduction velocity, thermal nociception, and intraepidermal and cornea nerve fiber density was determined. Glucose clearance was impaired in diabetic mice and significantly improved only with combination treatment and early intervention. Diabetes caused steatosis, slowing of motor and sensory nerve conduction velocity, thermal hypoalgesia and reduction in intraepidermal and cornea nerve fiber density. Treating diabetic mice with enalapril, α-lipoic acid or menhaden oil partially protected diabetic mice from these deficits, whereas the combination of these three treatments was more efficacious following early or late intervention. These studies suggest that a combination therapy may be more effective for treating neural complications of type 2 diabetes. •Menhaden (fish) oil, α-lipoic acid and enalapril singularly can improve diabetic peripheral neuropathy.•Combination therapy is more effective than monotherapy in treating diabetic peripheral neuropathy.•Diabetic peripheral neuropathy is treatable even after chronic hyperglycemia.•Diabetes-induced loss of intraepidermal nerve fibers and sub-epithelial corneal nerve fibers is reversible.
Details
- Title: Subtitle
- Early vs. late intervention of high fat/low dose streptozotocin treated C57Bl/6J mice with enalapril, α-lipoic acid, menhaden oil or their combination: Effect on diabetic neuropathy related endpoints
- Creators
- Matthew S Yorek - Department of Veterans Affairs Iowa City Health Care System, Iowa City, IA, 52246, USAAlexander Obrosov - Department of Internal Medicine, University of Iowa, Iowa City, IA, 52242, USAHanna Shevalye - Department of Internal Medicine, University of Iowa, Iowa City, IA, 52242, USALawrence J Coppey - Department of Internal Medicine, University of Iowa, Iowa City, IA, 52242, USARandy H Kardon - Department of Veterans Affairs Iowa City Health Care System, Iowa City, IA, 52246, USAMark A Yorek - Department of Veterans Affairs Iowa City Health Care System, Iowa City, IA, 52246, USA
- Resource Type
- Journal article
- Publication Details
- Neuropharmacology, Vol.116, pp.122-131
- DOI
- 10.1016/j.neuropharm.2016.12.022
- PMID
- 28025096
- PMCID
- PMC5385152
- NLM abbreviation
- Neuropharmacology
- ISSN
- 0028-3908
- eISSN
- 1873-7064
- Publisher
- Elsevier Ltd
- Grant note
- name: Department of Veterans Affairs, Veterans Health Administration, Office of Research and Development, Rehabilitation Research and Development, award: RX000889-04; name: Iowa City VA Center of Excellence for the Prevention and Treatment of Visual Loss, award: C9251-C (RHK); DOI: 10.13039/100000062, name: National Institute of Diabetes and Digestive and Kidney Diseases, award: DK107339-01
- Language
- English
- Date published
- 04/2017
- Academic Unit
- Iowa Neuroscience Institute; Internal Medicine; Ophthalmology and Visual Sciences
- Record Identifier
- 9983980053802771
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