■阿霉素(DOX)用于治疗各种癌症,具有良好的疗效。然而,由于其对各种器官和健康细胞的影响,其治疗用途受到限制。阿霉素可影响肾脏并引起毒性。证据表明,DOX通过氧化应激诱导肾毒性。
■在这项研究中,我们研究了线粒体移植对改善DOX对肾近端肾小管细胞(RPTCs)的线粒体和细胞毒性的影响。
■研究测量了7个毒性参数,包括细胞裂解,活性氧(ROS)的形成,线粒体膜电位(MMP)下降,GSH和GSSG含量,脂质过氧化(LPO),三磷酸腺苷(ATP)含量,和Caspase-3活性(凋亡的最终介质)。从Wistar大鼠肾制备活性新鲜线粒体。
■研究结果表明DOX在RPTC中引起细胞毒性。此外,DOX通过增加活性氧的水平诱导氧化应激,降低谷胱甘肽含量,和提高脂质过氧化。此外,它导致线粒体膜受损,caspase-3活性增加,ATP含量降低。线粒体移植,作为一种新的治疗方法,减少氧化应激,线粒体膜损伤,以及DOX在RPTCs中引起的细胞凋亡。此外,这种治疗方法增加了RPTC中的ATP含量。
■我们的研究表明,这种治疗方法可能有助于治疗药物诱导的肾毒性。
UNASSIGNED: Doxorubicin (DOX) is used in the treatment of various cancers and has good effectiveness. However, its therapeutic use is limited due to its effects on various organs and healthy cells. Doxorubicin can affect the kidneys and cause toxicity. Evidence shows that DOX induces nephrotoxicity through oxidative stress.
UNASSIGNED: In this research, we examined the effect of mitochondrial transplantation on improving mitochondrial and cellular toxicity caused by DOX on renal proximal tubular cells (RPTCs).
UNASSIGNED: The research measured 7 toxicity parameters, including cell lysis, reactive oxygen species (ROS) formation, mitochondrial membrane potential (MMP) decline, GSH and GSSG content, lipid peroxidation (LPO), adenosine triphosphate (ATP) content, and Caspase-3 activity (the final mediator of apoptosis). Active fresh mitochondria were prepared from Wistar rat kidney.
UNASSIGNED: The findings indicated that DOX caused cytotoxicity in RPTCs. Additionally, DOX induced oxidative stress by increasing the level of reactive oxygen species, reducing glutathione content, and elevating lipid peroxidation. Moreover, it led to damage to the mitochondrial membrane, increased caspase-3 activity, and decreased ATP content. Mitochondrial transplantation, as a new therapeutic approach, reduced oxidative stress, mitochondrial membrane damage, and apoptosis caused by DOX in RPTCs. Furthermore, this therapeutic approach increased the ATP content in RPTCs.
UNASSIGNED: Our study suggests that this therapeutic approach could be helpful in the treatment of drug-induced nephrotoxicity.