Instituto de Ciências Biomédicas (ICB), Universidade Federal do Rio de Janeiro (UFRJ), Rio de Janeiro, RJ, Brazil.
Laboratório de Pesquisa em Ciências Farmacêuticas (LAPESF), Universidade do Estado do Rio de Janeiro (UERJ), Manuel Caldeira de Alvarenga Avenue, 1.203, Rio de Janeiro, RJ, 23070-200, Brazil.
BMC Complement Med Ther. 2023 Aug 25;23(1):301. doi: 10.1186/s12906-023-04104-7.
Açaí, a Brazilian native fruit, has already been demonstrated to play a role in the progress of breast cancer and cardiotoxicity promoted by chemotherapy agents. Thus, the present study aimed to evaluate the combined use of açaí and the FAC-D chemotherapy protocol in a breast cancer model in vivo.
Mammary carcinogenesis was induced in thirty female Wistar rats by subcutaneous injection of 25 mg/kg 7,12-dimethylbenzanthracene (DMBA) in the mammary gland. After sixty days, the rats were randomized into two groups: treated with 200 mg/kg of either açaí extract or vehicle, via gastric tube for 45 consecutive days. The FAC-D protocol was initiated after 90 days of induction by intraperitoneal injection for 3 cycles with a 7-day break each. After treatment, blood was collected for haematological and biochemical analyses, and tumours were collected for macroscopic and histological analyses. In the same way, heart, liver, and kidney samples were also collected for macroscopic and histological analyses.
Breast cancer was found as a cystic mass with a fibrotic pattern in the mammary gland. The histological analysis showed an invasive carcinoma area in both groups; however, in the saline group, there was a higher presence of inflammatory clusters. No difference was observed regarding body weight, glycaemia, aspartate aminotransferase (AST), alanine aminotransferase (ALT), creatinine, and urea in either group. However, açaí treatment decreased creatine kinase (CK), creatine kinase MB (CKMB), troponin I and C-reactive protein levels and increased the number of neutrophils and monocytes. Heart histopathology showed normal myocardium in the açaí treatment, while the saline group presented higher toxicity effects with loss of architecture of cardiac tissue. Furthermore, the açaí treatment presented greater collagen distribution, increased hydroxyproline concentration and lower H2AX immunostaining in the heart samples.
Açaí decreased the number of inflammatory cells in the tumor environment and exhibited protection against chemotherapy drug cardiotoxicity with an increased immune response in animals. Thus, açaí can be considered a promising low-cost therapeutic treatment that can be used in association with chemotherapy agents to avoid heart damage.
巴西本土水果阿萨伊已被证明在乳腺癌的进展以及化疗药物引起的心脏毒性中发挥作用。因此,本研究旨在评估阿萨伊与 FAC-D 化疗方案联合应用于体内乳腺癌模型的效果。
通过在乳腺内皮下注射 25mg/kg 的 7,12-二甲基苯并蒽(DMBA)诱导 30 只雌性 Wistar 大鼠发生乳腺癌。60 天后,大鼠随机分为两组:连续 45 天通过胃管给予 200mg/kg 的阿萨伊提取物或载体。在诱导 90 天后,通过腹腔内注射开始 FAC-D 方案,每 7 天为一个周期,共 3 个周期。治疗后,采集血液进行血液学和生化分析,并采集肿瘤进行大体和组织学分析。同样,还采集心脏、肝脏和肾脏样本进行大体和组织学分析。
在乳腺中发现乳腺癌呈囊性肿块伴纤维化模式。组织学分析显示两组均存在浸润性癌区域;然而,在盐水组中,炎症簇的存在较高。两组的体重、血糖、天冬氨酸氨基转移酶(AST)、丙氨酸氨基转移酶(ALT)、肌酐和尿素均无差异。然而,阿萨伊治疗降低了肌酸激酶(CK)、肌酸激酶同工酶 MB(CKMB)、肌钙蛋白 I 和 C 反应蛋白水平,并增加了中性粒细胞和单核细胞的数量。心脏组织病理学显示阿萨伊治疗组的心肌正常,而盐水组则表现出更高的心脏毒性,伴有心肌组织结构丧失。此外,阿萨伊治疗组心脏样本中的胶原蛋白分布增加,羟脯氨酸浓度升高,H2AX 免疫染色减少。
阿萨伊减少了肿瘤环境中炎症细胞的数量,并表现出对化疗药物心脏毒性的保护作用,同时增强了动物的免疫反应。因此,阿萨伊可以被认为是一种有前途的低成本治疗方法,可以与化疗药物联合使用,以避免心脏损伤。