Alpha-lipoic acid and coenzyme Q10 combination ameliorates experimental diabetic neuropathy by modulating oxidative stress and apoptosis.
Administration, Oral
Animals
Apoptosis
/ drug effects
Biomarkers
/ metabolism
Blotting, Western
Caspase 3
/ genetics
Diabetes Mellitus, Experimental
/ complications
Diabetic Neuropathies
/ drug therapy
Drug Therapy, Combination
Enzyme-Linked Immunosorbent Assay
Ganglia, Spinal
/ drug effects
Male
Neuroprotective Agents
/ administration & dosage
Oxidative Stress
/ drug effects
Rats
Rats, Wistar
Thioctic Acid
/ administration & dosage
Ubiquinone
/ administration & dosage
Uncoupling Protein 2
/ genetics
Alpha-lipoic acid
Apoptosis
Coenzyme Q10
Diabetic neuropathy
Dorsal root ganglion neurons
Oxidative stress
Journal
Life sciences
ISSN: 1879-0631
Titre abrégé: Life Sci
Pays: Netherlands
ID NLM: 0375521
Informations de publication
Date de publication:
01 Jan 2019
01 Jan 2019
Historique:
received:
16
10
2018
revised:
24
10
2018
accepted:
25
10
2018
pubmed:
6
11
2018
medline:
8
1
2019
entrez:
6
11
2018
Statut:
ppublish
Résumé
Diabetic neuropathy (DN) is the most common complication of diabetes. Neuroprotective effects of alpha lipoic acid (ALA) and coenzyme Q10 (CoQ10) has been previously shown in DN, but underlying mechanisms involved not been exactly found. The present study explored the neuroprotective effects of ALA and Q10 combination in experimental DN by ameliorating oxidative stress and apoptosis. We investigated the effects of CoQ10 (10 mg/kg, orally, five weeks) and/or ALA (100 mg/kg, orally, five weeks) in STZ (45 mg/kg, i.p.)- induced DN in rats. After treatments motor function, oxidative stress biomarkers, ATP levels, expression of caspase 3 and UCP2 proteins were assessed by open-field, biochemical and ELISA methods and Western blot analysis. Dorsal root ganglion (DRG) neurons were histologically examined using H&E staining method. ALA and/or CoQ10 treatment significantly (p < 0.05) attenuated DN - induced motor function deficiency by modulating distance moved and velocity. ALA and/or CoQ10 treatment dramatically suppressed DN - induced oxidative stress which was associated with decrease in LPO and ROS and increase in GSH and TAC in DRG neurons. ALA and/or CoQ10 was proved to prevent apoptosis and degeneration of DRG neurons, which appears to be mediated by regulating the expression of caspase 3 and UCP2 proteins, inducing ATP and improving DN-induced changes in DRG neurons. We found maximum effectiveness with ALA and CoQ10 combination on mentioned factors. These results provide a possible basis of the underlying mechanism for application of ALA and CoQ10 combination in treatment of DN.
Identifiants
pubmed: 30393023
pii: S0024-3205(18)30684-2
doi: 10.1016/j.lfs.2018.10.055
pii:
doi:
Substances chimiques
Biomarkers
0
Neuroprotective Agents
0
Ucp2 protein, rat
0
Uncoupling Protein 2
0
Ubiquinone
1339-63-5
Thioctic Acid
73Y7P0K73Y
Casp3 protein, rat
EC 3.4.22.-
Caspase 3
EC 3.4.22.-
coenzyme Q10
EJ27X76M46
Types de publication
Journal Article
Langues
eng
Sous-ensembles de citation
IM
Pagination
101-110Informations de copyright
Copyright © 2018 Elsevier Inc. All rights reserved.