Chloramphenicol is a highly lipid-soluble broad-spectrum antibiotic for bacterial infections. Chloramphenicol inhibits protein synthesis by binding to the 50S subunit of the ribosome, thus acting as an antibacterial agent. Chloramphenicol can be used in the treatment of meningitis and cancer research[1-3].
Chloramphenicol inhibits the oxygen destabilizing transcription factor hypoxia-inducible factor 1α (HIF-1α) in hypoxic A549 and H1299 cells, and also inhibits mRNA levels of vascular endothelial growth factor and glucose transporter protein 1[1]. Chloramphenicol induces the expression of matrix metalloproteinase (MMP)-13, which leads to increased cancer cell invasion.Chloramphenicol activates c-Jun N-terminal kinase (JNK) and PI3K/Akt signaling, leading to the phosphorylation of c-Jun protein, and the activated c-Jun protein activates binding to the MMP-13 promoter and upregulate MMP-1 levels[2].
In MPTP-induced Parkinson's (PD) mouse models, Chloramphenicol (50 mg/kg) attenuates toxin-induced dopaminergic neuronal loss by blocking the target site of paraquat (PQ) action[3]. Chloramphenicol can inhibit the increase of body weight and liver weight induced by piperidol oxide (4-OH-tempo) and allopurinol (AP) in mice, and at the same time, chloramphenicol can induce a significant increase in lipid peroxidation during the formation of liver giant mitochondria[4].
References:
[1] Hsu HL, Liao PL, Cheng YW, Huang SH, Wu CH, Li CH, Kang JJ. Chloramphenicol Induces Autophagy and Inhibits the Hypoxia Inducible Factor-1 Alpha Pathway in Non-Small Cell Lung Cancer Cells. Int J Mol Sci. 2019 Jan 3;20(1):157.
[2] Li CH, Cheng YW, Liao PL, Yang YT, Kang JJ. Chloramphenicol causes mitochondrial stress, decreases ATP biosynthesis, induces matrix metalloproteinase-13 expression, and solid-tumor cell invasion. Toxicol Sci. 2010 Jul;116(1):140-50.
[3] Han J, Kim S J, Ryu M J, et al. Chloramphenicol Mitigates Oxidative Stress by Inhibiting Translation of Mitochondrial Complex I in Dopaminergic Neurons of Toxin‐Induced Parkinson’s Disease Model[J]. Oxidative Medicine and Cellular Longevity, 2019, 2019(1): 4174803.
[4] Matsuhashi T, Liu X R, Nishizawa Y, et al. Mechanism of the formation of megamitochondria in the mouse liver induced by chloramphenicol[J]. Toxicology letters, 1996, 86(1): 47-54.
Chloramphenicol是一种高脂溶性的针对细菌感染的广谱抗生素，Chloramphenicol通过与核糖体50S亚基结合来抑制蛋白质合成，从而起到抗菌的作用。Chloramphenicol可用于脑膜炎的治疗和癌症的研究[1-3]。
Chloramphenicol在缺氧的A549和H1299细胞中抑制氧不稳定转录因子缺氧诱导因子1α（HIF-1α），也可抑制血管内皮生长因子和葡萄糖转运蛋白1的mRNA水平[1]。Chloramphenicol可以诱导基质金属蛋白酶（MMP）-13的表达，从而导致癌细胞侵袭增加。Chloramphenicol激活c-Jun N末端激酶 (JNK) 和PI3K/Akt信号传导，导致c-Jun蛋白磷酸化，激活的c-Jun蛋白可以激活与MMP-13启动子的结合，并上调MMP-1的水平[2]。
在MPTP诱导的帕金森（PD）小鼠模型中，Chloramphenicol（50 mg/kg）通过阻断百草枯（PQ）作用的靶位点，减弱了毒素诱导的多巴胺能神经元损失[3]。Chloramphenicol可抑制哌啶醇氧化物（4-OH-TEMPO）和别嘌醇（AP）诱导的小鼠体重和肝重的增加，同时Chloramphenicol诱导肝脏巨型线粒体形成过程中脂质过氧化的显著增加[4]。