关键词: TRPM2 channel berberine cardiac damage curcumin cyclophosphamide

Mesh : Animals TRPM Cation Channels / metabolism Cyclophosphamide / toxicity adverse effects Male Rats Curcumin / pharmacology Berberine / pharmacology Myocardium / metabolism pathology Fibrosis Biomarkers / metabolism blood Lipids / blood Rats, Wistar Heart Diseases / chemically induced metabolism pathology prevention & control drug therapy

来  源:   DOI:10.1002/jbt.23783

Abstract:
Cyclophosphamide (CYP) is widely used to treat various types of cancer. In addition to the therapeutic properties of this drug, unfortunately, its side effects are still not fully understood. This study investigated the protective effect of curcumin (CURC) and berberine (BER) on CYP-induced cardiac damage. Thirty-six male rats were equally divided into the control, dimethyl sulfoxide (DMSO), CYP, CYP + CURC, CYP + BER and CYP + BER + CURC groups. Troponin-I, Creatine kinase-myocardial band (CK-MB), total cholesterol, triglyceride levels in serum samples, and reactive oxygen species (ROS), poly(ADP-ribose) polymerase-1 (PARP-1), and transient receptor potential melastatin 2 (TRPM2) channel levels in heart tissue were measured using an enzyme-linked immunoassay (ELISA) kit. In addition, histopathological examination and immunohistochemical investigation of the TRPM2 channel, fibroblast specific protein-1 (FSP1), transforming growth factor-beta- 1 (TGF-β1) and α-smooth muscle actin (α-SMA) expressions were determined in heart tissue. The CYP group\'s troponin-I, total cholesterol, triglyceride, CK-MB, ROS, PARP-1 and TRPM2 channel levels were higher than in the other groups in the ELISA measurements (p < 0.05). In contrast, these parameters in the group treated with CURC and BER together with CYP were lower than in the CYP group (p < 0.05). Additionally, CUR and BER reduced CYP-induced pathological damage, TRPM2, FSP1, TGF-β1 and α-SMA expressions. The data showed that CYP administration can cause cardiac damage by increasing the TRPM2 channel, TGF-β1, FSP1 and α-SMA expression levels. Therefore, we concluded that CURC and BER administration following CYP application may be used as therapeutic agents to prevent CYP-induced cardiac damage.
摘要:
环磷酰胺(CYP)广泛用于治疗各种类型的癌症。除了这种药物的治疗特性,不幸的是,其副作用仍未完全了解。研究姜黄素(CURC)和小檗碱(BER)对CYP诱导的心脏损伤的保护作用。36只雄性大鼠等分为对照组,二甲基亚砜(DMSO),CYP,CYP+CURC,CYP+BER和CYP+BER+CURC组。肌钙蛋白-I,肌酸激酶-心肌带(CK-MB),总胆固醇,血清样本中的甘油三酯水平,和活性氧(ROS),聚(ADP-核糖)聚合酶-1(PARP-1),使用酶联免疫分析(ELISA)试剂盒测量心脏组织中瞬时受体电位梅司他丁2(TRPM2)通道水平。此外,TRPM2通道的组织病理学检查和免疫组织化学研究,成纤维细胞特异性蛋白-1(FSP1),检测转化生长因子-β1(TGF-β1)和α-平滑肌肌动蛋白(α-SMA)在心脏组织中的表达。CYP组的肌钙蛋白-I,总胆固醇,甘油三酯,CK-MB,ROS,在ELISA测量中,PARP-1和TRPM2通道水平高于其他组(p<0.05)。相比之下,CURC和BER以及CYP治疗组的这些参数低于CYP组(p<0.05)。此外,CUR和BER减少CYP诱导的病理损伤,TRPM2、FSP1、TGF-β1和α-SMA表达。数据显示CYP给药可通过增加TRPM2通道引起心脏损伤,TGF-β1、FSP1和α-SMA表达水平。因此,我们得出的结论是,CYP应用后的CURC和BER可用作预防CYP引起的心脏损伤的治疗药物.
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