skip to main content
OSTI.GOV title logo U.S. Department of Energy
Office of Scientific and Technical Information

Title: Ofloxacin induces apoptosis in microencapsulated juvenile rabbit chondrocytes by caspase-8-dependent mitochondrial pathway

Abstract

Quinolones (QNs)-induced arthropathy is an important toxic effect in immature animals leading to restriction of their therapeutic use in pediatrics. However, the exact mechanism still remains unclear. Recently, we have demonstrated that ofloxacin, a typical QN, induces apoptosis of alginate microencapsulated juvenile rabbit joint chondrocytes by disturbing the {beta}{sub 1} integrin functions and inactivating the ERK/MAPK signaling pathway. In this study, we extend our initial observations to further elucidate the mechanism(s) of ofloxacin-induced apoptosis by utilizing specific caspase inhibitors. Pretreatment with both caspase-9-specific inhibitor zLEHD-fmk and caspase-8 inhibitor zIETD-fmk attenuated ofloxacin-induced apoptosis and activation of caspase-3 of chondrocyte in a concentration-dependent manner, as determined by fluorescent dye staining, enzyme activity assay and immunoblotting. Furthermore, the activation of caspase-9, -8 and -3 stimulated by ofloxacin was significantly inhibited in the presence of zIETD-fmk while pretreatment with zLEHD-fmk only blocked the activation of caspase-9 and -3. Ofloxacin also stimulated a concentration-dependent translocation of cytochrome c from mitochondria into the cytosol and a decrease of mitochondrial transmembrane potential, which was completely inhibited by zIETD-fmk. In addition, ofloxacin was found to increase the level of Bax, tBid, p53 in a concentration- and time-dependent manner. Taken together, The current results indicate that the caspase-8-dependent mitochondrialmore » pathway is primarily involved in the ofloxacin-induced apoptosis of microencapsulated juvenile rabbit joint chondrocytes.« less

Authors:
 [1];  [2];  [3]; ; ;  [1]
  1. National Beijing Center for Drug Safety Evaluation and Research, Beijing Institute of Pharmacology and Toxicology, 27 Taiping Road, Beijing 100850 (China)
  2. College of Vocational Technology, Inner Mongolia Agricultural University, Baotou 014100 (China)
  3. Tissue Engineering Research Center, Beijing Institute of Basic Medical Sciences, 27 Taiping Road, Beijing 100850 (China)
Publication Date:
OSTI Identifier:
21077892
Resource Type:
Journal Article
Journal Name:
Toxicology and Applied Pharmacology
Additional Journal Information:
Journal Volume: 226; Journal Issue: 2; Other Information: DOI: 10.1016/j.taap.2007.08.025; PII: S0041-008X(07)00401-2; Copyright (c) 2007 Elsevier Science B.V., Amsterdam, The Netherlands, All rights reserved; Country of input: International Atomic Energy Agency (IAEA); Journal ID: ISSN 0041-008X
Country of Publication:
United States
Language:
English
Subject:
60 APPLIED LIFE SCIENCES; ALGINATES; APOPTOSIS; DYES; ENZYME ACTIVITY; JUVENILES; MITOCHONDRIA; PEDIATRICS; RABBITS; TIME DEPENDENCE; TOXICITY; TRANSLOCATION

Citation Formats

Zhiguo, Sheng, Xiaojuan, Cao, Peng Shuangqing, Changyong, Wang, Qianqian, Li, Yimei, Wang, and Mifeng, Liu. Ofloxacin induces apoptosis in microencapsulated juvenile rabbit chondrocytes by caspase-8-dependent mitochondrial pathway. United States: N. p., 2008. Web. doi:10.1016/j.taap.2007.08.025.
Zhiguo, Sheng, Xiaojuan, Cao, Peng Shuangqing, Changyong, Wang, Qianqian, Li, Yimei, Wang, & Mifeng, Liu. Ofloxacin induces apoptosis in microencapsulated juvenile rabbit chondrocytes by caspase-8-dependent mitochondrial pathway. United States. https://doi.org/10.1016/j.taap.2007.08.025
Zhiguo, Sheng, Xiaojuan, Cao, Peng Shuangqing, Changyong, Wang, Qianqian, Li, Yimei, Wang, and Mifeng, Liu. Tue . "Ofloxacin induces apoptosis in microencapsulated juvenile rabbit chondrocytes by caspase-8-dependent mitochondrial pathway". United States. https://doi.org/10.1016/j.taap.2007.08.025.
@article{osti_21077892,
title = {Ofloxacin induces apoptosis in microencapsulated juvenile rabbit chondrocytes by caspase-8-dependent mitochondrial pathway},
author = {Zhiguo, Sheng and Xiaojuan, Cao and Peng Shuangqing and Changyong, Wang and Qianqian, Li and Yimei, Wang and Mifeng, Liu},
abstractNote = {Quinolones (QNs)-induced arthropathy is an important toxic effect in immature animals leading to restriction of their therapeutic use in pediatrics. However, the exact mechanism still remains unclear. Recently, we have demonstrated that ofloxacin, a typical QN, induces apoptosis of alginate microencapsulated juvenile rabbit joint chondrocytes by disturbing the {beta}{sub 1} integrin functions and inactivating the ERK/MAPK signaling pathway. In this study, we extend our initial observations to further elucidate the mechanism(s) of ofloxacin-induced apoptosis by utilizing specific caspase inhibitors. Pretreatment with both caspase-9-specific inhibitor zLEHD-fmk and caspase-8 inhibitor zIETD-fmk attenuated ofloxacin-induced apoptosis and activation of caspase-3 of chondrocyte in a concentration-dependent manner, as determined by fluorescent dye staining, enzyme activity assay and immunoblotting. Furthermore, the activation of caspase-9, -8 and -3 stimulated by ofloxacin was significantly inhibited in the presence of zIETD-fmk while pretreatment with zLEHD-fmk only blocked the activation of caspase-9 and -3. Ofloxacin also stimulated a concentration-dependent translocation of cytochrome c from mitochondria into the cytosol and a decrease of mitochondrial transmembrane potential, which was completely inhibited by zIETD-fmk. In addition, ofloxacin was found to increase the level of Bax, tBid, p53 in a concentration- and time-dependent manner. Taken together, The current results indicate that the caspase-8-dependent mitochondrial pathway is primarily involved in the ofloxacin-induced apoptosis of microencapsulated juvenile rabbit joint chondrocytes.},
doi = {10.1016/j.taap.2007.08.025},
url = {https://www.osti.gov/biblio/21077892}, journal = {Toxicology and Applied Pharmacology},
issn = {0041-008X},
number = 2,
volume = 226,
place = {United States},
year = {2008},
month = {1}
}