Santos Sara A, Amaral Ricardo G, Graça Ariel S, Gomes Silvana V F, Santana Fabrício P, de Oliveira Iza B, Andrade Luciana N, Severino Patrícia, de Albuquerque-Júnior Ricardo L C, Santos Sandra L, Souto Eliana B, Carvalho Adriana A
Department of Physiology, Federal University of Sergipe, São Cristóvão CEP 49100-000, Brazil.
Institute de Technology and Research (ITP), Tiradentes University, Aracaju CEP 49100-000, Brazil.
Toxics. 2023 Apr 14;11(4):375. doi: 10.3390/toxics11040375.
Medicinal plants have been commonly associated with chemotherapeutic treatments, as an approach to reduce the toxicological risks of classical anticancer drugs. The objective of this study was to evaluate the effects of combining the antineoplastic drug 5-fluorouracil (5-FU) with flowers extract (MRFE) to treat mice transplanted with sarcoma 180. Tumor inhibition, body and visceral mass variation, biochemical, hematological, and histopathological parameters were evaluated. The isolated 5-FU, 5-FU+MRFE 100 mg/kg/day, and 5-FU+MRFE 200 mg/kg/day reduced tumor growth; however, 5-FU+MRFE 200 mg/kg/day showed a more significant tumor reduction when compared to 5-FU alone. These results corroborated with the analysis of the tumor histopathological and immunodetection of the Ki67 antigen. In the toxicological analysis of the association 5-FU+MRFE 200 mg/kg/day, an intense loss of body mass was observed, possibly as a result of diarrhea. In addition, spleen atrophy, with a reduction in white pulp, leukopenia and thrombocytopenia, was observed in the 5-FU groups alone and associated with MRFE 200 mg/kg/day; however, there was no statistical difference between these groups. Therefore, the MRFE 200 mg/kg/day did not interfere in myelosuppressive action of 5-FU. In hematological analysis, body and visceral mass variation and biochemical parameters related to renal (urea and creatinine) and cardiac (CK-MB) function, no alteration was observed. In biochemical parameters related to liver function enzymes, there was a reduction in aspartate transaminase (AST) values in the 5-FU groups alone and associated with MRFE 200 mg/kg/day; however, there was no statistical difference between these groups. Therefore, the MRFE 200 mg/kg/day does not appear to influence enzyme reduction. The results of this study suggest that the association between the 5-FU+MRFE 200 can positively interfere with the antitumor activity, promoting the antineoplastic-induced reduction in body mass, while minimizing the toxicity of chemotherapy.
药用植物通常与化疗治疗相关联，作为一种降低传统抗癌药物毒理学风险的方法。本研究的目的是评估将抗肿瘤药物5-氟尿嘧啶（5-FU）与花朵提取物（MRFE）联合使用对移植肉瘤180的小鼠的治疗效果。评估了肿瘤抑制、身体和内脏质量变化、生化、血液学和组织病理学参数。单独使用5-FU、5-FU+MRFE 100mg/kg/天和5-FU+MRFE 200mg/kg/天均能抑制肿瘤生长；然而，与单独使用5-FU相比，5-FU+MRFE 200mg/kg/天显示出更显著的肿瘤缩小。这些结果与肿瘤组织病理学分析和Ki67抗原的免疫检测结果相符。在对5-FU+MRFE 200mg/kg/天联合用药的毒理学分析中，观察到体重严重下降，可能是腹泻所致。此外，单独使用5-FU组以及与200mg/kg/天的MRFE联合使用的组中均观察到脾脏萎缩，白髓减少，白细胞减少和血小板减少；然而，这些组之间没有统计学差异。因此，200mg/kg/天的MRFE不会干扰5-FU的骨髓抑制作用。在血液学分析、身体和内脏质量变化以及与肾脏（尿素和肌酐）和心脏（CK-MB）功能相关的生化参数方面，未观察到改变。在与肝功能酶相关的生化参数方面，单独使用5-FU组以及与200mg/kg/天的MRFE联合使用的组中天冬氨酸转氨酶（AST）值降低；然而，这些组之间没有统计学差异。因此，200mg/kg/天的MRFE似乎不会影响酶的降低。本研究结果表明，5-FU+MRFE 200联合使用可积极干扰抗肿瘤活性，促进抗肿瘤药物引起的体重减轻，同时将化疗毒性降至最低。
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