Sharifiaghdam Zeynab, Dalouchi Fereshteh, Sharifiaghdam Maryam, Shaabani Elnaz, Ramezani Fatemeh, Nikbakht Farnaz, Azizi Yaser
Student Research Committee, Iran University of Medical Sciences, Tehran, Iran.
Department of Physiology, School of Medicine, Iran University of Medical Sciences, Tehran, Iran.
Clin Exp Pharmacol Physiol. 2022 Jan;49(1):70-83. doi: 10.1111/1440-1681.13579. Epub 2021 Sep 7.
Doxorubicin (DOX) is one of the most widely used chemotherapy agents; however, its nonselective effect causes cardiotoxicity. Curcumin (Cur), a well known dietary polyphenol, could exert a significant cardioprotective effect, but the biological application of this substance is limited by its chemical insolubility. To overcome this limitation, in this study, we synthesised gold nanoparticles based on Cur (Cur-AuNPs). Ultraviolet-visible (UV-Vis) absorbance spectroscopy and transmission electron microscopy (TEM) were performed for the characterisation of synthesised NPs, and Fourier transform infrared (FTIR) spectroscopy were applied to detect Cur on the surface of AuNPs. Its cytotoxicity effect on H9c2 cells was evaluated using 3-(4,5-dimethylthiazol-2-yl)-2,5-diphenyltetrazolium bromide (MTT) assay. The biological efficacy of Cur-AuNPs was assessed after acute cardiotoxicity induction in BALB/c mice with DOX injection. The serum biomarkers, myocardial histological changes, and cardiomyocyte apoptosis were then measured. The results revealed that the heart protection by Cur-AuNPs is more effective than Cur alone. Heart protective effect of Cur-AuNPs was evident both in the short-term (24 hours) and long-term (14 days) study. The results of Cur-AuNPs400 after 24 hours of toxicity induction displayed the reduction of the cardiac injury serum biomarkers (LDH, CK-MB, cTnI, ADT, and ALT) and apoptotic proteins (Bax and Caspase-3), as well as increase of Bcl-2 anti-apoptotic proteins without any sign of interfibrillar haemorrhage and intercellular spaces in the heart tissue microscopic images. Our long-term study signifies that Cur-AuNPs400 in DOX-intoxicated mice could successfully inhibit body and heart weight loss in comparison to DOX group.
阿霉素(DOX)是使用最广泛的化疗药物之一;然而,其非选择性作用会导致心脏毒性。姜黄素(Cur)是一种著名的膳食多酚,可发挥显著的心脏保护作用,但该物质的生物学应用受到其化学不溶性的限制。为克服这一限制,在本研究中,我们基于姜黄素合成了金纳米颗粒(Cur-AuNPs)。采用紫外可见(UV-Vis)吸收光谱和透射电子显微镜(TEM)对合成的纳米颗粒进行表征,并应用傅里叶变换红外(FTIR)光谱检测金纳米颗粒表面的姜黄素。使用3-(4,5-二甲基噻唑-2-基)-2,5-二苯基四氮唑溴盐(MTT)法评估其对H9c2细胞的细胞毒性作用。在通过注射DOX诱导BALB/c小鼠急性心脏毒性后,评估Cur-AuNPs的生物学功效。然后测量血清生物标志物、心肌组织学变化和心肌细胞凋亡。结果显示,Cur-AuNPs对心脏的保护作用比单独使用姜黄素更有效。在短期(24小时)和长期(14天)研究中,Cur-AuNPs的心脏保护作用均很明显。在毒性诱导24小时后,Cur-AuNPs400的结果显示心脏损伤血清生物标志物(乳酸脱氢酶、肌酸激酶同工酶MB、心肌肌钙蛋白I、天门冬氨酸转移酶和丙氨酸转氨酶)和凋亡蛋白(Bax和半胱天冬酶-3)减少,以及抗凋亡蛋白Bcl-2增加,并且在心脏组织显微镜图像中没有任何肌原纤维间出血和细胞间隙的迹象。我们的长期研究表明,与DOX组相比,DOX中毒小鼠中的Cur-AuNPs400可以成功抑制体重和心脏重量减轻。