Seydi Enayatollah, Andalib Mahsa, Yaghoubi Sana, Fakhri Amir, Yuzugulen Jale, Arjmand Abdollah, Pourahmad Jalal
Department of Occupational Health and Safety Engineering, School of Health, Alborz University of Medical Sciences, Karaj, Iran.
Research Center for Health, Safety and Environment, Alborz University of Medical Sciences, Karaj, Iran.
Iran J Pharm Res. 2024 Mar 31;23(1):e146033. doi: 10.5812/ijpr-146033. eCollection 2024 Jan-Dec.
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.
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).
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.
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.
Our study suggests that this therapeutic approach could be helpful in the treatment of drug-induced nephrotoxicity.
阿霉素（DOX）用于治疗多种癌症且疗效良好。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。阿霉素会影响肾脏并导致毒性。有证据表明，DOX通过氧化应激诱导肾毒性。
在本研究中，我们研究了线粒体移植对改善DOX对肾近端小管细胞（RPTCs）造成的线粒体和细胞毒性的作用。
该研究测量了7个毒性参数，包括细胞裂解、活性氧（ROS）形成、线粒体膜电位（MMP）下降、谷胱甘肽（GSH）和氧化型谷胱甘肽（GSSG）含量、脂质过氧化（LPO）、三磷酸腺苷（ATP）含量以及半胱天冬酶-3活性（凋亡的最终介质）。从Wistar大鼠肾脏制备活性新鲜线粒体。
研究结果表明，DOX对RPTCs具有细胞毒性。此外，DOX通过增加活性氧水平、降低谷胱甘肽含量和提高脂质过氧化诱导氧化应激。此外，它还导致线粒体膜损伤、半胱天冬酶-3活性增加和ATP含量降低。线粒体移植作为一种新的治疗方法，可减轻DOX对RPTCs造成的氧化应激、线粒体膜损伤和凋亡。此外，这种治疗方法还增加了RPTCs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性肾毒性。
