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<p>Binge drinking (BD) is the predominant pattern of alcohol consumption among adolescents. It is clinically associated with cardiovascular and hepatic alterations due to its strong pro-oxidant effects. Folic acid (FA), a cardioprotective vitamin, is related to caveolins (Cav), proteins involved in cellular nitrosative balance. This study aims to evaluate BD as a possible cardiometabolic risk factor (CMRF) during adolescence by examining its effects on cardiac nitrosative equilibrium as well as the potential of FA supplementation to mitigate these effects. Four groups of adolescent rats were employed: control, BD (intraperitoneal alcohol), control FA-supplemented, and BD-FA-supplemented. Diets contained 2 ppm FA (control) or 8 ppm FA (supplemented). BD promoted several CMRFs, including insulin resistance. BD also induced cardiac oxidative stress, primarily through NADPH oxidase (NOX) activation. Notably, BD caused cardiac nitrosative stress by increasing nitric oxide synthase (NOS) isoforms (iNOS and eNOS), resulting in abnormally high NO levels. This redox imbalance affected cardiac function by increasing heart rate (HR). BD further led to vascular dysfunction with decreased systemic NO and elevated VEGF and Cav-1, increasing mean blood pressure (MBP). FA supplementation restored cardiac oxidative/nitrosative homeostasis, normalizing NO levels. Consequently, HR and MBP decreased, vascular function improved, and CMRFs were attenuated. The action of FA was partly mediated by increased Cav-1 levels in the heart and serum. These findings suggest that FA supplementation could be a promising strategy to mitigate cardiovascular alterations induced by BD in adolescents and potentially prevent the development of future cardiometabolic diseases.</p><p></p>

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Binge drinking as a potential cardiometabolic risk factor during adolescence in rats: novel protective antinitrosative mechanism of folic acid via caveolin-1

  • 期刊论文

  • 发表日期：

    2025年11月19日

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  • María del Carmen Gallego-López,
  • Fátima Nogales,
  • Inés Romero-Herrera,
  • Olimpia Carreras,
  • María Luisa Ojeda

摘要

Binge drinking (BD) is the predominant pattern of alcohol consumption among adolescents. It is clinically associated with cardiovascular and hepatic alterations due to its strong pro-oxidant effects. Folic acid (FA), a cardioprotective vitamin, is related to caveolins (Cav), proteins involved in cellular nitrosative balance. This study aims to evaluate BD as a possible cardiometabolic risk factor (CMRF) during adolescence by examining its effects on cardiac nitrosative equilibrium as well as the potential of FA supplementation to mitigate these effects. Four groups of adolescent rats were employed: control, BD (intraperitoneal alcohol), control FA-supplemented, and BD-FA-supplemented. Diets contained 2 ppm FA (control) or 8 ppm FA (supplemented). BD promoted several CMRFs, including insulin resistance. BD also induced cardiac oxidative stress, primarily through NADPH oxidase (NOX) activation. Notably, BD caused cardiac nitrosative stress by increasing nitric oxide synthase (NOS) isoforms (iNOS and eNOS), resulting in abnormally high NO levels. This redox imbalance affected cardiac function by increasing heart rate (HR). BD further led to vascular dysfunction with decreased systemic NO and elevated VEGF and Cav-1, increasing mean blood pressure (MBP). FA supplementation restored cardiac oxidative/nitrosative homeostasis, normalizing NO levels. Consequently, HR and MBP decreased, vascular function improved, and CMRFs were attenuated. The action of FA was partly mediated by increased Cav-1 levels in the heart and serum. These findings suggest that FA supplementation could be a promising strategy to mitigate cardiovascular alterations induced by BD in adolescents and potentially prevent the development of future cardiometabolic diseases.