Liu Hao, Wei Wei, Li Xiang
Institute of Clinical Pharmacology, Anhui Medical University, Engineering Technology Research Center of Anti-inflammatory and Immunodrugs in Anhui Province, Hefei.
Prostaglandins Other Lipid Mediat. 2009 Apr;88(3-4):63-7. doi: 10.1016/j.prostaglandins.2008.10.002. Epub 2008 Oct 22.
Inhibitors against cyclooxygenase-2 (COX-2), an inducible enzyme that catalyzes prostaglandin synthesis, are widely used in clinical. However, the potential hepatic toxicity of COX-2 inhibitors remains incompletely investigated. We report in this study that a clinically available COX-2 inhibitor, celecoxib, exacerbates porcine serum (PS)-induced hepatic fibrosis and induces hepatocellular necrosis in an experimental liver fibrosis model. Histological results revealed that although celecoxib by itself did not cause notable hepatic damages, it markedly enhanced hepatic fibrosis that had been initiated by PS. While PS alone did not cause any necrotic change in liver cells, the addition of celecoxib resulted in hepatocellular necrosis in PS-treated animals. Notably, celecoxib enhanced reduction of plasma prostaglandin E(2) (PGE(2)) levels induced by PS. Taken together, our results indicate that treatment with celecoxib may exacerbate liver fibrosis and cause hepatocellular necrosis. This may be associated with reduction in PGE(2) as an inheritance consequence of inhibition of COX-2.
环氧化酶-2（COX-2）是一种催化前列腺素合成的诱导酶，针对该酶的抑制剂在临床上广泛应用。然而，COX-2抑制剂潜在的肝毒性尚未得到充分研究。我们在本研究中报告，一种临床可用的COX-2抑制剂塞来昔布，在实验性肝纤维化模型中会加剧猪血清（PS）诱导的肝纤维化并导致肝细胞坏死。组织学结果显示，虽然塞来昔布本身不会引起明显的肝损伤，但它会显著加重由PS引发的肝纤维化。单独使用PS不会导致肝细胞发生任何坏死性变化，但在PS处理的动物中添加塞来昔布会导致肝细胞坏死。值得注意的是，塞来昔布会增强PS诱导的血浆前列腺素E2（PGE2）水平的降低。综上所述,我们的结果表明，塞来昔布治疗可能会加剧肝纤维化并导致肝细胞坏死。这可能与作为抑制COX-2的遗传后果的PGE2减少有关。
