Koral Lokman, Ovali Mehmet Akif, Tufekcioglu Nezahat Kubra, Karakilic Ersen, Adali Yasemen, Uzun Metehan
Department of Medical Oncology, Faculty of Medicine, Çanakkale Onsekiz Mart University, 17100, Çanakkale, Turkey.
Department of Physiology, Faculty of Medicine, Çanakkale Onsekiz Mart University, Çanakkale, Turkey.
Mol Biol Rep. 2021 Nov;48(11):7457-7465. doi: 10.1007/s11033-021-06763-6. Epub 2021 Oct 16.
The present study evaluates the development of edema, the change in the AQP3, AQP4, p53 and Bax gene expressions, and the protective effects of melatonin in rat hearts administered with cisplatin.
A total of 28 Wistar albino rats were divided into four groups. The vehicle was administered intraperitoneally (i.p.) to the rats in the control group. The melatonin group (Mel) received melatonin at a dose of 10 mg/kg for 13 days. The cisplatin group (Cis) received cisplatin on days 1, 5, 9 and 13 at a dose of 4 mg/kg. The rats in the cisplatin + melatonin (Cis+Mel) group underwent the procedures both in the Mel and Cis groups. Blood and left ventricular samples were taken and analyzed on day 14 of the study. AQP3, p53 and Bax gene expressions were found to be significantly increased following cisplatin administration compared to the control, while melatonin administration significantly decreased the expression of these genes (p < 0.05). Melatonin administration also significantly decreased the level of AQP4 gene expression compared to the cis. On histological examination, congestion, hemorrhage, extracellular and intracellular edema, and degenerative changes were significantly more common in the Cis than in the control. Melatonin administration significantly decreased intracellular edema (p = 0.010) and degenerative changes (p = 0.010), and the improvement in extracellular edema was close to statistical significance (p = 0.051) in melatonin.
These results indicate that melatonin had an ameliorative effect on myocardial edema and AQP channels, and that it may be used as a protective molecule against myocardial edema secondary to cisplatin administration.
本研究评估了顺铂给药大鼠心脏中水肿的发展、水通道蛋白3（AQP3）、水通道蛋白4（AQP4）、p53和Bax基因表达的变化以及褪黑素的保护作用。
总共28只Wistar白化大鼠被分为四组。对照组大鼠腹腔注射溶剂。褪黑素组（Mel）以10mg/kg的剂量接受褪黑素，持续13天。顺铂组（Cis）在第1、5、9和13天接受4mg/kg剂量的顺铂。顺铂+褪黑素（Cis+Mel）组的大鼠接受了Mel组和顺铂组的联合操作。在研究的第14天采集血液和左心室样本并进行分析。与对照组相比，顺铂给药后AQP3、p53和Bax基因表达显著增加，而褪黑素给药显著降低了这些基因的表达（p<0.05）。与顺铂组相比，褪黑素给药也显著降低了AQP4基因表达水平。组织学检查显示，与对照组相比，顺铂组充血、出血、细胞外和细胞内水肿以及退行性改变更为常见。褪黑素给药显著降低了细胞内水肿（p=0.010）和退行性改变（p=0.010），褪黑素对细胞外水肿的改善接近统计学意义（p=0.051）。
这些结果表明，褪黑素对心肌水肿和水通道蛋白通道具有改善作用，并且它可能用作预防顺铂给药继发的心肌水肿的保护分子。
