Nasrin Sadeghiyan Galeshkalami1, Mohammad Abdollahi2, Rezvan Najafi3, Maryam Baeeri4, Akram Jamshidzade5, Reza Falak6, Mohammad Davoodzadeh Gholami6, Gholamreza Hassanzadeh7, Tahmineh Mokhtari8, Shokoufeh Hassani4, Mahban Rahimifard4, Asieh Hosseini9. 1. Department of Pharmacology, Faculty of Pharmacy, Shiraz University of Medical Sciences, Shiraz, Iran. 2. Toxicology and Diseases Group, The Institute of Pharmaceutical Sciences (TIPS), Tehran University of Medical Science, Tehran, Iran; Department of Toxicology and Pharmacology, Faculty of Pharmacy, Tehran University of Medical Sciences, Tehran, Iran. 3. Research Center for Molecular Medicine, Hamadan University of Medical Sciences, Hamadan, Iran. 4. Toxicology and Diseases Group, The Institute of Pharmaceutical Sciences (TIPS), Tehran University of Medical Science, Tehran, Iran. 5. Pharmaceutical Sciences Research Center, Shiraz University of Medical Sciences, Shiraz, Iran. 6. Department of Immunology, School of Medicine, Iran University of Medical Sciences, Tehran, Iran. 7. Department of Anatomy, School of Medicine, Tehran University of Medical Sciences, Tehran, Iran. 8. Nervous System Stem Cells Research Center, Semnan University of Medical Sciences, Semnan, Iran; Department of Anatomy, School of Medicine, Semnan University of Medical Sciences, Semnan, Iran. 9. Razi Drug Research Center, Iran University of Medical Sciences, Tehran, Iran. Electronic address: hoseini.as@iums.ac.ir.
Abstract
AIMS: 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. MAIN METHODS: 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. KEY FINDINGS: 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. SIGNIFICANCE: These results provide a possible basis of the underlying mechanism for application of ALA and CoQ10 combination in treatment of DN.
AIMS: 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. MAIN METHODS: 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. KEY FINDINGS: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. SIGNIFICANCE: These results provide a possible basis of the underlying mechanism for application of ALA and CoQ10 combination in treatment of DN.
Authors: Giovanni Pagano; Carla Manfredi; Federico V Pallardó; Alex Lyakhovich; Luca Tiano; Marco Trifuoggi Journal: Inflamm Res Date: 2020-12-21 Impact factor: 4.575
Authors: Giovanni Pagano; Federico V Pallardó; Beatriz Porto; Maria Rosa Fittipaldi; Alex Lyakhovich; Marco Trifuoggi Journal: Antioxidants (Basel) Date: 2020-01-18
Authors: Giovanni Pagano; Federico V Pallardó; Alex Lyakhovich; Luca Tiano; Maria Rosa Fittipaldi; Maria Toscanesi; Marco Trifuoggi Journal: Int J Mol Sci Date: 2020-09-25 Impact factor: 5.923