作者：Fu-Tao; Zhang; Dan; Xing; Ming-Xing; D...ofloxacinmarbofloxacinersapoptosis
摘要：Quinolones (QNs) are widely used for their broad antibacterial spectrum and good antibacterial activities,desirable pharmacokinetic characteristics and few cross reactions with other therapeutic agents. However,QNs have adverse effects including chondrotoxicity in juvenile animals,so the use of QNs is contraindicated in children and adolescents. In regarding to the chondrotoxicity of QNs,numerous studies have been done. The current hypothesis suggests that QNs compete with the β1 integrin receptors residing on chondrocyte surface for extracellular Mg ions,which leads to alternation in β1 integrin expression,or function and eventually results in chondrocyte death. Stupack et al (2001)demonstrated that caspase-8 could be recruited to unligated integrins in adherent cells and further initiate apoptosis in a death receptor-independent manner. Sheng et al (2008) found that ofloxacin induced rabbit’s chondrocyte apoptosis by causing disturbance of β1 integrin functions and subsequently through caspase-8-dependent mitochondrial pathway.Apoptosis could be initiated through the stimulation of death receptors and through an intrinsic pathway from mitochondria. Santangelo and Bertone (2011) and Wu et al (2011) found that TNFα could be expressed in human primary condrocytes inducing by interleukin-1beta (IL-1) or lipopolysaccharide (LPS). However,to date there have not been sufficient results to support that signaling from the death receptors was involved in QNs-induced chondrocyte apoptosis.In addition,dilated cisternae of rough endoplasmic reticulum (ER) have been noticed in QNs-induced arthropathy.ER can participate in the initiation of apoptosis. Varieties of harmful cellular stimuli could lead to ERs (ER stress). Elevated ERs results in cellular apoptosis. But whether ERs mediates apoptosis in QNs-treated chondrocytes is not clear yet.In this study,we chose two QNs agents and chondrocytes were treated with ofloxacin and marbofloxacin at final concentrations of 20 μg / mL,50 μg / mL and 100 μg / mL respectively
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