Chronic treatment with resveratrol improves overactive bladder in obese mice via antioxidant activity.
The objective of the present work was to evaluate whether oral intake with resveratrol ameliorates overactive bladder in high-fat fed mice. Male C57BL6 mice fed with standard chow or high-fat diet to induce obesity received a two-week therapy with resveratrol (100mg/kg, given as a daily gavage). Weight and metabolic profile, together with cystometry and in vitro bladder contractions were evaluated. Measurements of gp91phox and SOD1 mRNA expressions and reactive-oxygen species (ROS) in bladder tissues, and serum TBARS were performed. Obese mice exhibited increases in body weight and epididymal fat mass, which were significantly reduced by oral treatment with resveratrol. Cystometric study in obese mice showed increases in non-voiding contractions, post-voiding pressure and voiding frequency that were reversed by resveratrol treatment. Likewise, the in vitro bladder overactivity in response to electrical-field stimulation (80V, 1-32Hz) or carbachol (1nM to 10mM) were normalized by resveratrol. The gp91phox and SOD1 mRNA expressions in bladder tissues were markedly higher in obese mice compared with lean group. In addition, ROS levels in bladder tissues and serum lipid peroxidation (TBARS assay) were markedly higher in obese compared with lean mice, all of which were reduced by resveratrol treatment. In lean group, resveratrol had no effect in any parameter evaluated. Our results show that two-week therapy of obese mice with resveratrol reduces the systemic and bladder oxidative stress, and greatly ameliorated the cystometry alterations and in vitro bladder overactivity. Resveratrol treatment could be an option to prevent obesity-associated overactive bladder.
Department of Pharmacology, Faculty of Medical Sciences, University of Campinas (UNICAMP), Campinas 13084-971, Brazil.
Eduardo C
EC
Alexandre
Department of Pharmacology, Faculty of Medical Sciences, University of Campinas (UNICAMP), Campinas 13084-971, Brazil.
Fabiano B
FB
Calmasini
Department of Pharmacology, Faculty of Medical Sciences, University of Campinas (UNICAMP), Campinas 13084-971, Brazil.
Mariana G
MG
de Oliveira
Hematology and Hemotherapy Center, University of Campinas (UNICAMP), Campinas 13083-878, Brazil.
Fábio H
FH
Silva
Department of Structural and Functional Biology, Institute of Biology, University of Campinas (UNICAMP), Campinas 13083-862, Brazil.
Carmem P V
CPV
da Silva
Department of Pharmacology, Faculty of Medical Sciences, University of Campinas (UNICAMP), Campinas 13084-971, Brazil.
Diana M
DM
André
Hematology and Hemotherapy Center, University of Campinas (UNICAMP), Campinas 13083-878, Brazil.
Flávia C
FC
Leonardo
Department of Structural and Functional Biology, Institute of Biology, University of Campinas (UNICAMP), Campinas 13083-862, Brazil.
Maria A
MA
Delbin
Department of Pharmacology, Faculty of Medical Sciences, University of Campinas (UNICAMP), Campinas 13084-971, Brazil. Electronic address: edson.antunes@uol.com.br.
Edson
E
Antunes
D000284:Administration, Oral; D000818:Animals; D019440:Anti-Obesity Agents / Q000008:administration & dosage / Q000494:pharmacology* / Q000627:therapeutic use; D000975:Antioxidants / Q000008:administration & dosage / Q000494:pharmacology* / Q000627:therapeutic use; D001835:Body Weight / Q000187:drug effects; D059305:Diet, High-Fat / Q000009:adverse effects; D015971:Gene Expression Regulation, Enzymologic / Q000187:drug effects; D008297:Male; D008562:Membrane Glycoproteins / Q000235:genetics; D051379:Mice; D008810:Mice, Inbred C57BL; D009130:Muscle, Smooth / Q000187:drug effects / Q000378:metabolism; D000074662:NADPH Oxidase 2; D019255:NADPH Oxidases / Q000235:genetics; D009765:Obesity / Q000150:complications* / Q000209:etiology; D018384:Oxidative Stress / Q000187:drug effects; D012333:RNA, Messenger / Q000235:genetics / Q000378:metabolism; D000077185:Resveratrol; D013267:Stilbenes / Q000008:administration & dosage / Q000494:pharmacology* / Q000627:therapeutic use; D000072105:Superoxide Dismutase-1 / Q000235:genetics; D013997:Time Factors; D001743:Urinary Bladder / Q000187:drug effects / Q000378:metabolism; D053201:Urinary Bladder, Overactive / Q000150:complications* / Q000188:drug therapy* / Q000235:genetics / Q000378:metabolism
D019440:Anti-Obesity Agents; D000975:Antioxidants; D008562:Membrane Glycoproteins; D012333:RNA, Messenger; D013267:Stilbenes; D000072105:Superoxide Dismutase-1; C488842:Cybb protein, mouse; D000074662:NADPH Oxidase 2; D019255:NADPH Oxidases; D000077185:Resveratrol
Cystometry; NADPH oxidase; Obesity; Reactive-oxygen species; Superoxide dismutase; gp91phox