Departamento de Química, Centro de Ciências Naturais e Exatas, Universidade Federal de Santa Maria, 97105-900, Santa Maria, RS, Brazil.
Magnes Res. 2013 Jan-Feb;26(1):32-40. doi: 10.1684/mrh.2013.0334.
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.
本研究旨在通过将其摄入与高脂肪（HF）饮食相结合，建立氢氯噻嗪（HCTZ）毒性的啮齿动物模型。大鼠喂食 16 周的对照饮食或 HF 饮食，补充或不补充不同剂量的 HCTZ。与 HF 饮食一样，HCTZ 导致果糖胺水平显著升高。HCTZ 和 HF 饮食摄入导致镁和钾水平显著降低，以及肝脏脂质过氧化和维生素 C 增加。重要的是，发现镁和葡萄糖水平之间以及镁和果糖胺水平之间存在负相关。HCTZ 与 HF 饮食的联合使用导致与葡萄糖稳态相关的生化参数进一步恶化，并进一步增加肝氧化应激。我们的结果表明，HCTZ 或 HF 饮食的慢性摄入会引起代谢变化，这些变化与胰岛素抵抗的发展一致。此外，HF 饮食和 HCTZ 治疗的联合使用可能会加剧其中一些生化改变，这表明该模型可能有助于研究 HCTZ 的代谢毒性。
