- 作者: Cheng-Haung Wang; Yann-Jang Chen; Tsung-Hsing Lee; Yi-Shen Chen; Bruno Jawan; Kuo-Sheng Hung; Cheng-Nan Lu; Jong-Kang Liu
- 作者服務機構: Department of Biological Sciences, National Sun Yat-Sun Yat-sen University, Departments of Anesthesiology, Neurosurgery and Chinese Medicine, Kaohsiung Chang-Gung Memorial Hospital, Kahsiung, and Department of Life Sciences, National Yang-Ming University, Taipei, Taiwan, ROC
- 中文摘要: --
- 英文摘要: Liver injury is known to often progress even after thehepatotoxicant is dissipated.The hydrolytic enzyme cal-pain,which is released from dying hepatocytes, destroysthe surrounding cells and results in progression of inju-ry. Therefore, control of calpain activation may be a suit-able therapeutic intervention in cases of fulminant hepat-ic failure. This study evaluated the effects of a potent cell-permeable calpain inhibitor, MDL28170, and its mecha-nisms of action on thioacetamide (TAA)-induced hepato-toxicity in mice.We found that MDL28170 significantlydecreased mortality and change in serum transaminaseafter TAA administration.The necroinflammatory re-sponse in the liver was also suppressed.Furthermore, asignificant suppression of hepatocyte apoptosis could befound by terminal deoxynucleotidyl transferase-me-diated deoxyuridine triphosphate nick-end labeling as-say. The upregulation of inducible nitric oxide synthase(iNOS)and tumor necrosis factor-α(TNF-α),both ofwhich are known to mediate the propagation of in-flammation, was abolished.MDL2810 also effectivelyblocked hepatic stellate cell activation,which is assumedto be the early step in liver fibrosis. These results demon-strated that MDL28170 attenuated TAA-induced acuteliver failure by inhibiting hepatocyte apoptosis, abrogat-ing iNOS and TNF-α mRNA upregulation and blockinghepatic stellate cell activation.
- 中文關鍵字: --
- 英文關鍵字: --