Pamidronate Attenuates Oxidative Stress and Energetic Metabolism Changes but Worsens Functional Outcomes in Acute Doxorubicin-Induced Cardiotoxicity in Rats

被引：13

作者：

de Carvalho, Paula Bernardo ^{[1
]}

Goncalves, Andrea de Freitas ^{[1
]}

Correa Alegre, Patricia Helena ^{[1
]}

Azevedo, Paula Schmidt ^{[1
]}

Roscani, Meliza Goi ^{[1
]}

Bergamasco, Carolina Marabesi ^{[1
]}

Modesto, Pamela N. ^{[1
]}

Fernandes, Ana Angelica ^{[1
]}

Minicucci, Marcos Ferreira ^{[1
]}

Rupp Paiva, Sergio Alberto ^{[1
]}

Antonio, Leonardo ^{[1
]}

Zornoff, Mamede ^{[1
]}

Polegato, Bertha Furlan ^{[1
]}

机构：

[1] Univ Estadual Paulista UNESP, Fac Med Botucatu, Botucatu, SP, Brazil

来源：

CELLULAR PHYSIOLOGY AND BIOCHEMISTRY | 2016年 / 40卷 / 3-4期

基金：

巴西圣保罗研究基金会;

关键词：

Isolated heart study; Left ventricular dysfunction; Matrix metalloproteinase; Hypocalcaemia; MATRIX METALLOPROTEINASE-2; HEART-FAILURE; INDUCED CARDIOMYOPATHY; ZOLEDRONIC ACID; ANTITUMOR-ACTIVITY; BREAST-CANCER; IN-VITRO; ADRIAMYCIN; CELLS; MODEL;

D O I：

10.1159/000452558

中图分类号：

Q2 [细胞生物学];

学科分类号：

071009 ; 090102 ;

摘要：

Background: Cardiotoxicity is the major side effect of doxorubicin. As mechanisms that are involved in cardiotoxicity are ambiguous, new methods for attenuating cardiotoxicity are needed. Recent studies have shown that bisphosphonates can decrease oxidative stress. Therefore, the objective of this study was to evaluate the effect of pamidronate on preventing acute doxorubicin-induced cardiotoxicity. Methods: Sixty-four male Wistar rats were allocated into four groups: the control group (C), the pamidronate group (P), the doxorubicin group (D) and the doxorubicin/pamidronate group (DP). The rats in the P and DP groups received pamidronate injections (3 mg/kg, IP) After 24 hours, the rats in the D and DP groups received doxorubicin injections (20 mg/kg, IP). Forty-eight hours after doxorubicin injection, the rats were killed. Echocardiography, isolated heart study and biochemical analysis were performed. Results: Doxorubicin-induced acute cardiotoxicity showed increased matrix metalloproteinases (MMP)-2 activation, oxidative damage and induced alterations in myocardial energetic metabolism. Pamidronate did not inhibit MMP-2 activation but attenuated oxidative stress and improved myocardial energetic metabolism. Regarding cardiac function, the DP group exhibited a decrease in the left ventricular ejection fraction in the echocardiography and a decrease in +dP/dt in the isolated heart study compared with other groups. The same DP group presented serum hypocalcaemia. Conclusions: Despite its ability to reduce oxidative stress and improve energy metabolism in the heart, pamidronate worsened systolic function in rats treated with doxorubicin, and therefore we cannot recommend its use in conjunction with anthracycline chemotherapy. (C) 2016 The Author(s) Published by S Karger AG, Basel

引用

页码：431 / 442

页数：12

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