Metronomic chemotherapy is a relevant strategy that uses low doses of antineoplastic drugs for sustained periods to control tumor growth, an alternative frequently utilized in veterinary patients. This work aimed to evaluate the toxic effects of a metronomic oral dose of methotrexate (MTX) for 45 days in tumor-free Wistar rats when compared with control animals. Clinical alterations, body weight, food, and water intake were monitored daily, and bone marrow suppression, hematological, biochemical, and histopathological analyses were performed at three points (days 30, 45, and 60). MTX-treated animals did not demonstrate severe systemic involvement. At 30 days, compared with control animals, MTX-treated animals showed significant leukocytosis (11.9 ± 2.3 vs. 7.8 ± 0.2 10⁶/μL; P < .05) and augmentation of immature myeloid populations from bone marrow (9.0 ± 0.8 vs. 6.5 ± 1.5%; P < .05), and at 60 days, treated animals showed significant neutrophilia (35.0 ± 11.0 vs. 23.00 ± 3.0%; P < .05), depletion of bone marrow lymphocytes (8.2 ± 0.7 vs. 11.5 ± 1.9%; P < .05), and immature myeloid populations (7.2 ± 0.7 vs. 8.3 ± 0.6%; P < .05). At a histopathological level, splenic hypoplasia and respiratory inflammatory lesions were significant when compared with control animals, presenting mild to moderate myelotoxicity, immune suppression, and associated clinical compromise that persisted beyond treatment withdrawal. This suggested that MTX metronomic toxicity should not be neglected owing to the observed residual side-effects and special care should be taken regarding myelosuppression.

节律化学疗法是一种相关策略，该策略持续使用低剂量抗肿瘤药来控制肿瘤的生长，这是兽医患者中经常使用的一种替代方法。这项工作旨在评估与对照组动物相比，在无肿瘤的Wistar大鼠中以甲氨蝶呤（MTX）的节律口服剂量连续45天的毒性作用。每天监测临床变化，体重，食物和水的摄入量，并在三个时间点（第30、45和60天）进行骨髓抑制，血液学，生化和组织病理学分析。经MTX处理的​​动物未表现出严重的全身性受累。与对照组动物相比，在30天时，MTX处理的​​动物显示出明显的白细胞增多（11.9±2.3对7.8±0.2 10 ⁶ /μL；P  <.05）和来自骨髓的未成熟髓细胞种群的增加（9.0±0.8 vs. 6.5±1.5％; P  <.05），在60天时，治疗的动物显示出明显的中性粒细胞增多（35.0±11.0 vs 23.00±3.0） ％; P  <.05），骨髓淋巴细胞的耗竭（8.2±0.7 vs. 11.5±1.9％; P  <.05）和未成熟的髓细胞群体（7.2±0.7 vs. 8.3±0.6％; P <.05）。在组织病理学水平上，与对照动物相比，脾发育不全和呼吸道炎性病变显着，表现出轻度至中度的骨髓毒性，免疫抑制以及相关的临床损害，这种损害一直持续到停药后。这表明，由于观察到的残留副作用，不应忽略MTX的基因组毒性，并应特别注意骨髓抑制。