The role of AQP3 and AQP4 channels in cisplatin‑induced cardiovascular edema and the protective efect of melatonin

Abstract

Background The present study evaluates the development of edema, the change in the AQP3, AQP4, p53 and Bax gene expressions, and the protective efects of melatonin in rat hearts administered with cisplatin. Methods and Results 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 signifcantly increased following cisplatin administration compared to the control, while melatonin administration signifcantly decreased the expression of these genes (p < 0.05). Melatonin administration also signifcantly decreased the level of AQP4 gene expression compared to the cis. On histological examination, congestion, hemorrhage, extracellular and intracellular edema, and degenerative changes were signifcantly more common in the Cis than in the control. Melatonin administration signifcantly decreased intracellular edema (p = 0.010) and degenerative changes (p = 0.010), and the improvement in extracellular edema was close to statistical signifcance (p = 0.051) in melatonin. Conclusions These results indicate that melatonin had an ameliorative efect on myocardial edema and AQP channels, and that it may be used as a protective molecule against myocardial edema secondary to cisplatin administration.