Sattar Tayyba, Jilani Kashif, Parveen Khalida, Mushataq Zahid, Nawaz Haq, Khan Maham Abdul Bari
Department of Biochemistry, University of Agriculture, Faisalabad, Pakistan.
Department of Zoology, Wildlife and Fisheries, University of Agriculture, Faisalabad, Pakistan.
Dose Response. 2022 Apr 13;20(2):15593258221093853. doi: 10.1177/15593258221093853. eCollection 2022 Apr-Jun.
Methotrexate (MTX) is a common chemotherapeutical agent and folate antagonist with reported apoptotic activity in nucleated cells. The presented research work was planned to investigate the eryptotic effects of methotrexate after the exposure of erythrocytes to therapeutical doses (10-15 μM) of methotrexate. Eryptosis and the role of calcium in the stimulation of membrane blebbing were evaluated through the determination of mean cell volume. Oxidative stress induced by methotrexate (10-15 μM) was determined by antioxidative enzyme activities. Cytotoxic activity against human erythrocytes was examined through hemolysis assay. Exposure of erythrocytes to methotrexate results in significant reduction of superoxide dismutase, catalase, and superoxide dismutase activities at 10 and 15 μM in comparison to the untreated cells. Erythrocytes mean cell volume (MCV) was increased after 48 hours exposure of erythrocytes to methotrexate (10 μM). Significantly increased hemolysis percentage was observed at 10 μM after 48 hours incubation of erythrocytes with methotrexate. The results of the study suggested that the therapeutical doses (10-15 μM) of methotrexate may lead to increase in eryptotic and hemolytic activity of erythrocytes through free radical generation and subsequent calcium entry.
甲氨蝶呤（MTX）是一种常见的化疗药物和叶酸拮抗剂，据报道在有核细胞中具有凋亡活性。本研究旨在探讨红细胞暴露于治疗剂量（10 - 15μM）的甲氨蝶呤后其发生红细胞凋亡的效应。通过测定平均细胞体积评估红细胞凋亡及钙在刺激膜泡形成中的作用。通过抗氧化酶活性测定甲氨蝶呤（10 - 15μM）诱导的氧化应激。通过溶血试验检测对人红细胞的细胞毒性活性。与未处理细胞相比，红细胞暴露于10μM和15μM的甲氨蝶呤后，超氧化物歧化酶、过氧化氢酶和超氧化物歧化酶活性显著降低。红细胞暴露于甲氨蝶呤（10μM）48小时后，平均细胞体积（MCV）增加。红细胞与甲氨蝶呤孵育48小时后，在10μM时观察到溶血百分比显著增加。研究结果表明，治疗剂量（10 - 15μM）的甲氨蝶呤可能通过自由基生成和随后的钙内流导致红细胞凋亡和溶血活性增加。
