ABSTRACT

Doxorubicin (Dox) is an anthracycline antibiotic with antineoplastic activity. Acetylsalicylic acid (Asa) is recommended for use as a prophylactic for thromboembolism during treatment of cancers. We investigated liver toxicity due to combined use of Dox and Asa in chemotherapy regimens. We used 140 Swiss albino mice divided into four main groups: control, Dox, Asa, and Dox + Asa. Each group was subdivided into seven subgroups based on time of sacrifice, i.e., 6, 12, 24, 48 h and 7, 14, 21 days. Quantitative and histopathological changes in liver were assessed by light microscopy and stereology. The portal triad area of the Dox and Dox + Asa groups was increased significantly compared to controls at 6 h, whereas in the Asa group, the means were similar to controls. Assessment of histopathology indicated an increased time-dependent degeneration and necrosis of liver tissues in mice in the Dox and Dox + Asa groups. The protective effects of Asa were not evident in Dox + Asa group. When Dox and Asa were administered together, degenerative changes were greater than for in the group that was given Dox alone. We found that Asa and Dox combined therapy increased tissue damage.

摘要

多柔比星 (Dox) 是一种具有抗肿瘤活性的蒽环类抗生素。乙酰水杨酸 (Asa) 被推荐用作癌症治疗期间血栓栓塞的预防剂。我们研究了化疗方案中联合使用 Dox 和 Asa 引起的肝毒性。我们使用了 140 只瑞士白化小鼠，分为四个主要组：对照、Dox、Asa 和 Dox + Asa。根据处死时间，即6、12、24、48小时和7、14、21天，每组被细分为七个亚组。通过光学显微镜和体视学评估肝脏的定量和组织病理学变化。与对照组相比，Dox 和 Dox + Asa 组的门户三联征区域在 6 小时时显着增加，而在 Asa 组中，平均值与对照组相似。组织病理学评估表明，Dox 和 Dox + Asa 组小鼠肝组织的时间依赖性变性和坏死增加。Asa的保护作用在Dox+Asa组中不明显。当 Dox 和 Asa 一起给药时，退行性变化比单独给予 Dox 的组更大。我们发现 Asa 和 Dox 联合治疗增加了组织损伤。