Aslam Hafiz Muhammad, Sohail Azka, Shahid Ammara, Khan Maham Abdul Bari, Sharif Muhammad Umar, Kausar Razia, Nawab Samia, Farooq Waqas, Jilani Kashif, Rasheed Majeeda
Department of Biochemistry, University of Agriculture, Faisalabad - Pakistan.
Department of Internal Medicine, Amna Anayat Medical College, Sheikhupura - Pakistan.
Drug Target Insights. 2024 Oct 7;18:78-83. doi: 10.33393/dti.2024.3060. eCollection 2024 Jan-Dec.
Levofloxacin, a fluoroquinolone, is an extensively used antibiotic effective against both positively and negatively staining bacteria. It works by inhibiting bacterial topoisomerase type II and topoisomerase type IV, resulting in impaired DNA synthesis and bacterial cell death. Eryptosis is another term for apoptotic cell death of erythrocyte marked by cell shrinkage, phosphatidylserine (PS) flipping, and membrane blebbing.
The intent of the present research was to look at the eryptotic effect of levofloxacin by exposing erythrocytes to therapeutical doses (7, 14 µM) of levofloxacin for 48 hours. Cell size evaluation, PS subjection to outside, and calcium channel inhibition were carried out to investigate eryptosis. Oxidative stress generated by levofloxacin was measured as a putative mechanism of eryptosis using glutathione peroxidase (GPx), superoxide dismutase (SOD), and catalase activities. Similarly, hemolysis measurements demonstrated levofloxacin's cytotoxic effect.
Our findings showed that therapeutic doses of levofloxacin can cause a considerable decline in antioxidant enzymes activities, as well as induce cell shrinkage, PS externalization, and hemolysis in erythrocytes. The role of calcium in triggering erythrocyte shrinkage was also confirmed.
In conclusion, our findings showed that the indicated levofloxacin doses caused oxidative stress, which leads to erythrocyte death via eryptosis and hemolysis. These findings emphasize the importance of using levofloxacin with caution and the need for additional research to mitigate these side effects.
左氧氟沙星是一种氟喹诺酮类药物，是一种广泛使用的抗生素，对革兰氏阳性菌和革兰氏阴性菌均有效。它通过抑制细菌II型拓扑异构酶和IV型拓扑异构酶发挥作用，导致DNA合成受损和细菌细胞死亡。红细胞凋亡性死亡是红细胞凋亡的另一种说法，其特征为细胞皱缩、磷脂酰丝氨酸（PS）外翻和细胞膜起泡。
本研究的目的是通过将红细胞暴露于治疗剂量（7、14µM）的左氧氟沙星中48小时，观察其对红细胞凋亡的影响。进行细胞大小评估、PS外翻检测和钙通道抑制实验以研究红细胞凋亡。使用谷胱甘肽过氧化物酶（GPx）、超氧化物歧化酶（SOD）和过氧化氢酶活性来测量左氧氟沙星产生的氧化应激，将其作为红细胞凋亡的一种可能机制。同样，溶血测量显示了左氧氟沙星的细胞毒性作用。
我们的研究结果表明，治疗剂量的左氧氟沙星可导致抗氧化酶活性显著下降，并诱导红细胞皱缩、PS外翻和溶血。钙在引发红细胞皱缩中的作用也得到了证实。
总之，我们的研究结果表明，所示剂量的左氧氟沙星会引起氧化应激，进而通过红细胞凋亡和溶血导致红细胞死亡。这些发现强调了谨慎使用左氧氟沙星的重要性，以及开展更多研究以减轻这些副作用的必要性。
