title: Hydrochlorothiazide and high-fat diets reduce plasma magnesium levels and increase hepatic oxidative stress in rats.
abstract: This study was designed to develop a rodent model of hydrochlorothiazide (HCTZ) toxicity by associating its intake with a high-fat (HF) diet. Rats were fed for 16 weeks with a control diet or with an HF diet supplemented or not with different doses of HCTZ. HCTZ, in a similar way to the HF diet, caused a significant increase in fructosamine levels. HCTZ and HF diet intake caused a significant reduction in magnesium and potassium levels, as well as an increase in lipid peroxidation and vitamin C in liver. Importantly, negative correlations were found between magnesium and glucose levels as well as between magnesium and fructosamine levels. The association between HCTZ and the HF diet caused additional worsening of biochemical parameters related to glucose homeostasis, and further increased hepatic oxidative stress. Our results suggest that chronic intake of HCTZ or an HF diet causes metabolic changes that are consistent with the development of insulin resistance. In addition, the association of an HF diet and HCTZ treatment can exacerbate some of these biochemical alterations, suggesting that this model might be useful for studying HCTZ metabolic toxicity.
authors: Departamento de Química, Centro de Ciências Naturais e Exatas, Universidade Federal de Santa Maria, 97105-900, Santa Maria, RS, Brazil. jbtrocha@yahoo.com.br
authors: Marinei Cristina Pereira
authors: MC
authors: Ribeiro
authors: Daiana Silva de
authors: DS
authors: Avila
authors: Nilda Berenice de Vargas
authors: NB
authors: Barbosa
authors: Daiane Francine
authors: DF
authors: Meinerz
authors: Emily Pansera
authors: EP
authors: Waczuk
authors: Waseem
authors: W
authors: Hassan
authors: João Batista Teixeira
authors: JB
authors: Rocha
mesh_terms: D000818:Animals; D001205:Ascorbic Acid / Q000378:metabolism; D001835:Body Weight / Q000187:drug effects; D059305:Diet, High-Fat; D019270:Fructosamine / Q000378:metabolism; D006852:Hydrochlorothiazide / Q000494:pharmacology*; D015227:Lipid Peroxidation / Q000187:drug effects; D008099:Liver / Q000187:drug effects / Q000378:metabolism / Q000473:pathology*; D008274:Magnesium / Q000097:blood*; D008297:Male; D018384:Oxidative Stress / Q000187:drug effects*; D011188:Potassium / Q000097:blood; D050050:Protein Carbonylation / Q000187:drug effects; D051381:Rats; D017208:Rats, Wistar; D017392:Thiobarbituric Acid Reactive Substances / Q000378:metabolism
chemical_list: D017392:Thiobarbituric Acid Reactive Substances; D006852:Hydrochlorothiazide; D019270:Fructosamine; D008274:Magnesium; D001205:Ascorbic Acid; D011188:Potassium
keywords: high-fat diet; hydrochlorothiazide; hyperglycemia; magnesium; oxidative stress