Doxorubicin (DOX) treatment has been associated with cardiotoxicity. Therefore, it is crucial to search for a therapeutic that can effectively mitigate DOX-induced cardiotoxicity. This study was conducted to investigate the protective effects of valsartan (VAL) against DOX-induced cardiotoxicity. Sprague–Dawley rats were divided into four treatment groups: Group I: Control, Group II: VAL (30 mg/kg, ip), Group III: DOX (15 mg/kg, ip), and Group IV: VAL + DOX (30 + 15 mg/kg, ip). All groups were treated every other day for 14 days. Blood was isolated for biochemical and metabolomics studies, and sections of the heart were also analyzed for histopathological and immunohistochemical alterations to detect changes in P53, BAX, BCL-2, and P62 expression. The combination of VAL + DOX resulted in a marked decrease in cardiac biomarker enzymes (aminotransferase and creatine phosphokinase) compared to DOX monotherapy. In addition, the histopathological examination of the VAL + DOX combination revealed a low percentage of fibrosis and inflammation. Immunohistochemical expression of p53 and BAX was significantly reduced, whereas BCL-2 expression was significantly increased in the VAL + DOX treatment group compared to DOX monotherapy. Also, the combination of VAL + DOX reverses the negative effect of DOX on nuclear p62 expression. Analysis of serum metabolites showed that DOX monotherapy reduced the number of several amino acids, whereas the combination of VAL + DOX restored these metabolic pathways. This study revealed the potential cardioprotective effect of VAL, which may provide novel and promising approaches for managing cardiotoxicity induced by DOX.

中文翻译：

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缬沙坦对阿霉素诱导的心脏毒性的保护作用：体内组织病理学和代谢组学研究

多柔比星 (DOX) 治疗与心脏毒性有关。因此，寻找一种能够有效减轻 DOX 诱导的心脏毒性的治疗方法至关重要。本研究旨在研究缬沙坦 (VAL) 对 DOX 诱导的心脏毒性的保护作用。Sprague-Dawley 大鼠分为四个治疗组：I 组：对照组，II 组：VAL（30 mg/kg，ip），III 组：DOX（15 mg/kg，ip），IV 组：VAL + DOX（ 30 + 15 毫克/公斤，腹腔注射）。所有组每隔一天接受一次治疗，持续 14 天。分离血液用于生化和代谢组学研究，还分析了心脏切片的组织病理学和免疫组织化学变化，以检测 P53、BAX、BCL-2 和 P62 表达的变化。与 DOX 单一疗法相比，VAL + DOX 的组合导致心脏生物标志物酶（转氨酶和肌酸磷酸激酶）显着降低。此外，VAL + DOX 组合的组织病理学检查显示纤维化和炎症的百分比较低。与 DOX 单药治疗相比，VAL + DOX 治疗组中 p53 和 BAX 的免疫组织化学表达显着降低，而 BCL-2 表达显着增加。此外，VAL + DOX 的组合逆转了 DOX 对核 p62 表达的负面影响。血清代谢物分析表明，DOX 单一疗法减少了几种氨基酸的数量，而 VAL + DOX 的组合恢复了这些代谢途径。这项研究揭示了 VAL 的潜在心脏保护作用，