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The Cholinergic Drug Galantamine Alleviates Oxidative Stress Alongside Anti-inflammatory and Cardio-Metabolic Effects in Subjects With the Metabolic Syndrome in a Randomized Trial.
- Source :
-
Frontiers in immunology [Front Immunol] 2021 Mar 11; Vol. 12, pp. 613979. Date of Electronic Publication: 2021 Mar 11 (Print Publication: 2021). - Publication Year :
- 2021
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Abstract
- Background: The metabolic syndrome (MetS) is an obesity-associated disorder of pandemic proportions and limited treatment options. Oxidative stress, low-grade inflammation and altered neural autonomic regulation, are important components and drivers of pathogenesis. Galantamine, an acetylcholinesterase inhibitor and a cholinergic drug that is clinically-approved (for Alzheimer's disease) has been implicated in neural cholinergic regulation of inflammation in several conditions characterized with immune and metabolic derangements. Here we examined the effects of galantamine on oxidative stress in parallel with inflammatory and cardio-metabolic parameters in subjects with MetS. Trial Design and Methods: The effects of galantamine treatment, 8 mg daily for 4 weeks or placebo, followed by 16 mg daily for 8 weeks or placebo were studied in randomly assigned subjects with MetS ( n = 22 per group) of both genders. Oxidative stress, including superoxide dismutase (SOD), catalase (CAT), and glutathione peroxidase activities, lipid and protein peroxidation, and nitrite levels were analyzed before and at the end of the treatment. In addition, plasma cytokine and adipokine levels, insulin resistance (HOMA-IR) and other relevant cardio-metabolic indices were analyzed. Autonomic regulation was also examined by heart rate variability (HRV) before treatment, and at every 4 weeks of treatment. Results: Galantamine treatment significantly increased antioxidant enzyme activities, including SOD [+1.65 USOD/mg protein, [95% CI 0.39-2.92], P = 0.004] and CAT [+0.93 nmol/mg, [95% CI 0.34-1.51], P = 0.01], decreased lipid peroxidation [thiobarbituric acid reactive substances [log scale 0.72 pmol/mg, [95% CI 0.46-1.07], P = 0.05], and systemic nitrite levels [log scale 0.83 μmol/mg protein, [95% CI 0.57-1.20], P = 0.04] compared with placebo. In addition, galantamine significantly alleviated the inflammatory state and insulin resistance, and decreased the low frequency/high frequency ratio of HRV, following 8 and 12 weeks of drug treatment. Conclusion: Low-dose galantamine alleviates oxidative stress, alongside beneficial anti-inflammatory, and metabolic effects, and modulates neural autonomic regulation in subjects with MetS. These findings are of considerable interest for further studies with the cholinergic drug galantamine to ameliorate MetS.<br />Competing Interests: VP and KT have published patents (US 8,865,641 B2 and US 8,003,632 B2) broadly relevant to this work and have assigned their rights to the Feinstein Institutes for Medical Research. The remaining authors declare that the research was conducted in the absence of any commercial or financial relationships that could be construed as a potential conflict of interest.<br /> (Copyright © 2021 Sangaleti, Katayama, De Angelis, Lemos de Moraes, Araújo, Lopes, Camacho, Bortolotto, Michelini, Irigoyen, Olofsson, Barnaby, Tracey, Pavlov and Consolim Colombo.)
- Subjects :
- Adult
Anti-Inflammatory Agents pharmacology
Biomarkers
Cholinesterase Inhibitors pharmacology
Cytokines metabolism
Female
Galantamine pharmacology
Heart Rate
Hemodynamics
Humans
Inflammation Mediators metabolism
Male
Metabolome
Middle Aged
Young Adult
Anti-Inflammatory Agents therapeutic use
Cholinesterase Inhibitors therapeutic use
Galantamine therapeutic use
Metabolic Syndrome drug therapy
Metabolic Syndrome metabolism
Myocardium metabolism
Oxidative Stress drug effects
Subjects
Details
- Language :
- English
- ISSN :
- 1664-3224
- Volume :
- 12
- Database :
- MEDLINE
- Journal :
- Frontiers in immunology
- Publication Type :
- Academic Journal
- Accession number :
- 33776997
- Full Text :
- https://doi.org/10.3389/fimmu.2021.613979