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1.
Appl Physiol Nutr Metab ; 46(9): 1133-1142, 2021 Sep.
Article in English | MEDLINE | ID: mdl-33740389

ABSTRACT

The effect of oral glutathione (GSH) supplementation was studied in obese subjects with and without type 2 diabetes (T2DM) on measures of glucose homeostasis and markers of oxidative stress. Twenty subjects (10 patients with T2DM and 10 obese subjects) were recruited for the study, and randomized in a double-blinded placebo-controlled manner to consume either 1000 mg GSH per day or placebo for 3 weeks. Before and after the 3 weeks insulin sensitivity was measured with the hyperinsulinemic-euglycemic clamp and a muscle biopsy was obtained to measure GSH and skeletal muscle mitochondrial hydrogen peroxide (H2O2) emission rate. Whole body insulin sensitivity increased significantly in the GSH group. Skeletal muscle GSH was numerically increased (∼19%) in the GSH group; no change was seen in GSH to glutathione disulfide ratio. Skeletal muscle mitochondrial H2O2 emission rate did not change in response to the intervention and neither did the urinary excretion of the RNA oxidation product 8-oxo-7,8-dihydroguanosine or the DNA oxidation product 8-oxo-7,8-dihydro-2'-deoxyguanosine (8-oxodG), although 8-oxodG decreased as a main effect of time. Oral GSH supplementation improves insulin sensitivity in obese subjects with and without T2DM, although it does not alter markers of oxidative stress. The study has been registered in clinicaltrials.gov (NCT02948673). Novelty: Reduced glutathione supplementation increases insulin sensitivity in obese subjects with and without T2DM. H2O2 emission rate from skeletal muscle mitochondria was not affected by GSH supplementation.


Subject(s)
Diabetes Mellitus, Type 2/physiopathology , Dietary Supplements , Glutathione/administration & dosage , Insulin Resistance/physiology , Obesity/physiopathology , Administration, Oral , Biomarkers/metabolism , Blood Glucose/metabolism , Diabetes Mellitus, Type 2/metabolism , Dietary Supplements/adverse effects , Glucose Tolerance Test , Glutathione/adverse effects , Glutathione/blood , Glutathione/metabolism , Glutathione Disulfide/metabolism , Humans , Hydrogen Peroxide/metabolism , Middle Aged , Mitochondria, Muscle/metabolism , Muscle, Skeletal/metabolism , Obesity/metabolism , Oxidative Stress , Oxygen Consumption
2.
PLoS One ; 15(5): e0233788, 2020.
Article in English | MEDLINE | ID: mdl-32470081

ABSTRACT

In pre-hypertension, moderate control of blood pressure (BP) can be obtained by a nutritional approach. The effects of a diet enriched with defatted larvae of the mealworm Tenebrio molitor (Coleoptera: Tenebrionidae) (TM) endowed with ACE inhibitory activity was studied in both spontaneously hypertensive rats (SHR) and in the age-matched normotensive Wistar Kyoto strain. These were fed for 4 weeks with standard laboratory rodent chow supplemented with or without TM or captopril. In SHR, the TM diet caused a significant reduction in BP, heart rate and coronary perfusion pressure, as well as an increase in red blood cell glutathione/glutathione disulphide ratio. Rat brain slices of SHR were more resistant to oxidative stress and contained lower levels of inflammatory cytokines, while vascular and liver enzyme-activities were not affected. These results suggest that TM can be considered a new functional food that can lower BP in vivo and thus control cardiovascular-associated risk factors such as hypertension.


Subject(s)
Blood Pressure , Dietary Supplements , Heart Rate , Hypertension/diet therapy , Animals , Antihypertensive Agents/pharmacology , Captopril/pharmacology , Hypertension/drug therapy , Larva , Male , Rats , Rats, Inbred SHR , Rats, Inbred WKY , Tenebrio
3.
PLoS One ; 7(1): e29930, 2012.
Article in English | MEDLINE | ID: mdl-22238677

ABSTRACT

Different studies reported the presence of oxidized (carbonylated) albumin in the extravascular pool, but not in the intravascular one of cigarette smokers. In this study we attempted to explain this apparent discrepancy exposing human serum albumin (HSA) to aqueous cigarette smoke extract (CSE). CSE induces HSA carbonylation and oxidation of the HSA Cys34 sulfhydryl group. An antioxidant action of glutathione, cysteine, and its synthetic derivative N-acetylcysteine was observed only at supra-physiological concentrations, suggesting that physiological (plasma) concentrations of glutathione and cysteine in the low micromolar range are ineffective in preventing cigarette smoke-induced oxidation of HSA. Differently, human erythrocytes resulted to be protective towards CSE-induced oxidation (carbonylation and thiol oxidation) of both HSA and total human plasma proteins.


Subject(s)
Cytoprotection , Erythrocytes/physiology , Serum Albumin/drug effects , Serum Albumin/metabolism , Smoke/adverse effects , Acetylcysteine/pharmacology , Cysteine/chemistry , Cysteine/metabolism , Cytoprotection/drug effects , Dose-Response Relationship, Drug , Drug Evaluation, Preclinical , Glutathione/analysis , Glutathione/blood , Glutathione/metabolism , Humans , Osmolar Concentration , Oxidation-Reduction/drug effects , Oxidative Stress/drug effects , Oxidative Stress/physiology , Serum Albumin/chemistry , Smoking/adverse effects , Smoking/metabolism , Sulfhydryl Compounds/metabolism
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