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Evaluation of biomarkers of oxidative and glicative stress, inflammatory status e energy metabolism in mice under an experimental model of obesity and insulin resistance treated with pentoxifylline

Abstract

A combination among rapid urbanization, nutrition transition, and sedentary lifestyle accounts for the epidemic proportions of type 2 diabetes mellitus (T2DM), which is characterized by insulin resistance and pancreatic dysfunction. In uncontrolled DM, microvascular and macrovascular complications are observed. Impairments caused by glicative and oxidative stress (due to hyperglycemia) and dyslipidemia participate in the onset of these complications, mainly the diabetic nephropathy and the cardiovascular diseases. New therapeutic strategies should be studied to prevent or treat the micro and macrovascular complications of DM, reducing the morbidity and mortality of the disease. It has been observed that phosphodiesterase (PDE) inhibitors are promising in the prevention/treatment of T2DM complications, highlighting pentoxifylline (PTX), a non-specific PDE inhibitor. Using diverse experimental DM models and different experimental approaches, it has been shown that PTX has antioxidant, anti-glicative and anti-inflammatory activities. In addition, PDE inhibitors are also able to stimulate the thermogenic activity of brown adipocytes, a strategy that can be useful to reduce the obesity induced by high-fat diet. With the identification of the branched fatty acid esters of hydroxy fatty acids (FAHFA), lipids related to the increased insulin sensitivity, a new perspective has been open to investigate the mechanisms related to the benefits of PTX. The objective of the present project is to study the effects of the treatment of mice under an experimental model of obesity and insulin resistance with PTX on biomarkers of oxidative and glicative stress, inflammatory status and energy metabolism, as well as to measure the levels of FAHFA in serum and adipose tissues. (AU)

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Scientific publications
(References retrieved automatically from Web of Science and SciELO through information on FAPESP grants and their corresponding numbers as mentioned in the publications by the authors)
COSTA, MARIANA CAMPOS; OLIVEIRA LIMA, TAYRA FERREIRA; ARCARO, CARLOS ALBERTO; INACIO, MAIARA DESTRO; BATISTA-DUHARTE, ALEXANDER; CARLOS, IRACILDA ZEPPONE; SPOLIDORIO, LUIS CARLOS; ASSIS, RENATA PIRES; BRUNETTI, IGUATEMY LOURENCO; BAVIERA, AMANDA MARTINS. Trigonelline and curcumin alone, but not in combination, counteract oxidative stress and inflammation and increase glycation product detoxification in the liver and kidney of mice with high-fat diet-induced obesity. JOURNAL OF NUTRITIONAL BIOCHEMISTRY, v. 76, . (16/23644-9)
INACIO, MAIARA DESTRO; COSTA, MARIANA CAMPOS; OLIVEIRA LIMA, TAYRA FERREIRA; FIGUEIREDO, INGRID DELBONE; MOTTA, BRUNO PEREIRA; SPOLIDORIO, LUIS CARLOS; ASSIS, RENATA PIRES; BRUNETTI, IGUATEMY LOURENCO; BAVIERA, AMANDA MARTINS. Pentoxifylline mitigates renal glycoxidative stress in obese mice by inhibiting AGE/RAGE signaling and increasing glyoxalase levels. Life Sciences, v. 258, p. 14-pg., . (16/23644-9)

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