The study aimed to explore the effects of local anesthetic bupivacaine on bladder cancer cells in vivo and in vitro . The cytotoxicity was detected by MTT assay. Apoptosis was measured by Hoechst 33342 staining and TUNEL. The contents of Fe 2+ , Malondialdehyde (MDA), Glutathione (GSH) and reactive oxygen species (ROS) were evaluated by the corresponding kit. Mitochondrial membrane potential was assessed by JC-1 kit. HE staining, TUNEL and immunohistochemistry were used to detect the xenografted tumors. Protein expression was estimated by Western blot. Bupivacaine significantly inhibited the activity of T24 cells and 5637 cells at 0.25–16 mM. Bupivacaine promoted cell apoptosis with increased concentration. bupivacaine inhibited the expression of Bcl-2 and increased the expression of Bax and cytochrome C. Moreover, bupivacaine amplified the level of Fe 2+ and ROS, and restrained the expression of cystine/glutamic acid reverse transporter (xCT) and glutathione peroxidase 4 (GPX4). Further results showed that bupivacaine decreased mitochondrial membrane potential, reduced GSH, and increased MDA levels. Besides, bupivacaine attenuated the phosphorylation of PI3K, Akt, and mTOR. In addition, bupivacaine suppressed the growth of xenografted tumors, induced apoptosis and ferroptosis, and inhibited the activity of PI3K/AKT signaling pathway in xenografted tumors. Bupivacaine could induce apoptosis and ferroptosis by inhibiting PI3K/Akt signaling pathway in bladder cancer cells.

Taxifolin suppressed the toxicity and THP-1 cell adhesion to HUVECs induced by Cr(vi) via regulating the p38 MAPK and JNK pathways.

Background and purpose: A high risk of brain injury has been reported with the usage of general anesthetics such as propofol in infants. Experimental data indicated that oxidative stress and inflammation are involved in the neurotoxicity induced by propofol. Febuxostat is a novel anti-gout agent recently reported to exert an anti-inflammatory effect. The present study aims to investigate the protective property of febuxostat against the cytotoxicity of propofol in brain endothelial cells as well as the underlying preliminary mechanism. Methods: The 3-(4,5-dimethylthiazol-2-yl)-2,5-diphenyltetrazolium bromide (MTT) assay was utilized to screen the optimized incubation concentration of febuxostat. bEnd.3 brain endothelial cells were stimulated with 2% propofol in the presence or absence of febuxostat (10, 20 μM) for 24 h. The lactate dehydrogenase (LDH) release assay was conducted to detect cytotoxicity. The reactive oxygen species (ROS) levels were evaluated using dichloro-dihydro-fluorescein diacetate (DCFH-DA) staining, and the concentration of reduced glutathione (GSH) was determined using a commercial kit. The expressions of TNF-α, IL-6, IL-12, CXCL-1, PDPN, CXCL8, VCAM-1, and E-selectin were determined using a quantitative real-time polymerase chain reaction (qRT-PCR) and an enzyme-linked immunosorbent assay (ELISA). Western blot and qRT-PCR were utilized to determine the expressions of COX-2 and KLF6. The production of PGE 2 was evaluated by ELISA. Results: First, increased LDH release induced by propofol was significantly suppressed by febuxostat. The oxidative stress (elevated ROS levels and decreased GSH level) induced by propofol was alleviated by febuxostat. Second, the upregulated inflammatory factors (TNF-α, IL-6, and IL-12), pro-inflammatory chemokines (CXCL-1, PDPN, and CXCL8), adhesion molecules (VCAM-1 and E-selectin), and inflammatory mediators (COX-2 and PGE 2 ) induced by propofol were greatly downregulated by febuxostat. Lastly, the expression of KLF6 was significantly suppressed by propofol but greatly elevated by febuxostat. Conclusion: Febuxostat prevented the cytotoxicity of propofol in brain endothelial cells by alleviating oxidative stress and inflammatory response through KLF6.