The Acetylcholinesterase Inhibitor Galantamine Ameliorates Oxidative Stress in Subjects with the Metabolic Syndrome

Abstract

The metabolic syndrome (MetS) is an obesity‐driven disorder with pandemic proportions and limited treatment options. Oxidative stress, low‐grade inflammation and altered autonomic regulation, are important components of MetS pathophysiology. We recently reported that galantamine, an acetylcholinesterase inhibitor and an FDA‐approved drug (for Alzheimer’s disease) alleviates the inflammatory state in MetS subjects. Here we examined the effects of galantamine on oxidative stress in parallel with inflammatory and cardio‐metabolic parameters in subjects with MetS. The effects of galantamine treatment, 8 mg daily for 4 weeks, 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. Plasma cytokine and adipokine levels, insulin resistance (HOMA‐IR) and other relevant cardio‐metabolic indices were also determined. Autonomic regulation was also examined by heart rate variability (HRV) before treatment, and at every 4 weeks of treatment. Galantamine treatment significantly increased antioxidant enzyme activities, including SOD (+1.65 USOD/mg protein, P=0.004) and CAT (+0.93 nmol/mg, P=0.011), decreased lipid peroxidation (thiobarbituric acid reactive substances, −5.45 pmol/mg, P=0.053) and systemic nitrite levels (−0.05 nit/mg protein, P=0.038) 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. In conclusion, a low‐dose galantamine treatment alleviates oxidative stress, alongside beneficial anti‐inflammatory, and metabolic effects, and modulates autonomic regulation in subjects with MetS. These findings are of considerable interest for further studies with galantamine to ameliorate MetS pathophysiology.