Shafiee Fatemeh, Safaeian Leila, Gorbani Fatemeh
Department of Pharmaceutical Biotechnology, School of Pharmacy and Pharmaceutical Sciences, Isfahan University of Medical Sciences, Isfahan, I.R. Iran.
Department of Pharmacology and Toxicology and Isfahan Pharmaceutical Sciences Research Center, School of Pharmacy and Pharmaceutical Sciences, Isfahan University of Medical Sciences, Isfahan, I.R. Iran.
Res Pharm Sci. 2023 Jan 19;18(2):149-158. doi: 10.4103/1735-5362.367794. eCollection 2023 Apr.
Some chemotherapeutic drugs are associated with an increased risk of cardiotoxicity in patients. Protocatechuic acid (PCA) is a phenolic acid with valuable cardiovascular, chemo-preventive, and anticancer activities. Recent studies have shown the cardioprotective effects of PCA in several pathological conditions. This investigation aimed to assess the possible protective effects of PCA on cardiomyocytes against toxicities caused by anti-neoplastic agents, doxorubicin (DOX), and arsenic trioxide (ATO).
H9C2 cells were exposed to DOX (1 μM) or ATO (35 μM) after 24 h pretreatment with PCA (1-100 μM). MTT and lactate dehydrogenase (LDH) tests were used to define cell viability or cytotoxicity. Total oxidant and antioxidant capacities were evaluated by measuring hydroperoxides and ferric-reducing antioxidant power (FRAP) levels. Expression of the TLR4 gene was also quantitatively estimated by real-time polymerase chain reaction.
FINDINGS/RESULTS: PCA showed a proliferative effect on cardiomyocytes and significantly enhanced cell viability and reduced cytotoxicity of DOX and ATO during MTT and LDH assays. Pretreatment of cardiomyocytes with PCA significantly decreased hydroperoxide levels and elevated FRAP value. Moreover, PCA meaningfully decreased TLR4 expression in DOX-and ATO-treated cardiomyocytes.
In conclusion, antioxidant and cytoprotective activities were found for PCA versus toxicities caused by DOX and ATO in cardiomyocytes. However, further investigations are recommended to assess its clinical value for the prevention and treatment of cardiotoxicity induced by chemotherapeutic agents.
一些化疗药物会使患者发生心脏毒性的风险增加。原儿茶酸（PCA）是一种具有重要心血管、化学预防和抗癌活性的酚酸。最近的研究表明，PCA在几种病理状况下具有心脏保护作用。本研究旨在评估PCA对心肌细胞抵抗抗肿瘤药物阿霉素（DOX）和三氧化二砷（ATO）所致毒性的可能保护作用。
用PCA（1 - 100 μM）预处理24小时后，将H9C2细胞暴露于DOX（1 μM）或ATO（35 μM）。采用MTT和乳酸脱氢酶（LDH）试验来确定细胞活力或细胞毒性。通过测量氢过氧化物和铁还原抗氧化能力（FRAP）水平来评估总氧化剂和抗氧化剂能力。还通过实时聚合酶链反应定量估计TLR4基因的表达。
在MTT和LDH试验中，PCA对心肌细胞显示出增殖作用，并显著提高细胞活力，降低DOX和ATO的细胞毒性。用PCA预处理心肌细胞可显著降低氢过氧化物水平并提高FRAP值。此外，PCA可显著降低DOX和ATO处理的心肌细胞中TLR4的表达。
总之，发现PCA对DOX和ATO所致心肌细胞毒性具有抗氧化和细胞保护活性。然而，建议进一步研究以评估其在预防和治疗化疗药物引起的心脏毒性方面的临床价值。
