Flubendazole

New uses of old drugs hold great promise for clinical translation. Flubendazole, an FDA‐approved antiparasitic drug, has been shown to target p53 and promote apoptosis in glioblastoma (GBM) cells. However, its damaging mechanism in GBM remains elusive. Herein, we explored the ferroptosis‐inducing ability of flubendazole on GBM cells. After treating glioma cell lines U251 and LN229 with the flubendazole (DMSO <1‰), cell viability was inhibited in a concentration‐dependent manner (IC50 for LN229 = 0.5331 μM, IC50 for U251 = 0.6809 μM), attributed to the induction of ferroptosis, as evidenced by increased MDA levels, accumulation of ROS and lipid peroxides, change in mitochondrial membrane potential and structure. Protein analysis related to ferroptosis showed upregulation of TFRC, DMT1 and p53, alongside downregulation of xCT, FHC and GPX4 (p < 0.05). All‐atom docking studies demonstrated that flubendazole bound closely with xCT, and TFRC, validating its role in inducing glioma ferroptosis via modulation of these proteins. Notably, flubendazole could damage the glioblastoma stem cells (GSC) that are typically resistant to other therapies, thereby possessing advantages in stopping glioma recurrence. This study delved into the mechanisms of flubendazole‐induced ferroptosis in glioma, broadening its application and providing new ideas for new uses of other old drugs.

Compounds originating from animal husbandry can pollute surface water through the application of manure to soil. Typically, grab sampling is employed to detect these residues, which only provides information on the concentration at the time of sampling. To better understand the emission patterns of these compounds, we utilized passive samplers in surface water to collect data at eight locations in a Dutch agricultural region, during different time intervals. As a passive sampler, we chose the integrative-based Speedisk® hydrophilic DVB. In total, we targeted 46 compounds, among which 25 antibiotics, three hormones, nine antiparasitics, and nine disinfectants. From these 46 compounds, 22 compounds accumulated in passive samplers in amounts above the limit of quantification in at least one sampling location. Over the 12-week deployment period, a time integrative uptake pattern was identified in 53% of the examined cases, with the remaining 47% not displaying this behavior. The occurrences without this behavior were primarily associated with specific location, particularly the most upstream location, or specific compounds. Our findings suggest that the proposed use of passive samplers, when compared in this limited context to traditional grab sampling, may provide enhanced efficiency and potentially enable the detection of a wider array of compounds. In fact, a number of compounds originating from animal husbandry activities were quantified for the first time in Dutch surface waters, such as flubendazole, florfenicol, and tilmicosine. The set-up of the sampling campaign also allowed to distinguish between different pollution levels during sampling intervals on the same location. This aspect gains particular significance when considering the utilization of different compounds on various occasions, hence, it has the potential to strengthen ongoing monitoring and mitigation efforts.