Hosseini Mir-Jamal, Hassanbeigloo Aysan, Abbasi Hamideh, Arjmand Abdollah, Sherkat Fatemeh, Pourahmad Jalal
Zanjan Applied Pharmacology Research Center, Zanjan University of Medical Sciences, Zanjan, Iran.
Department of Toxicology and Pharmacology, School of Pharmacy, Shahid Beheshti University of Medical Sciences, Tehran, Iran.
Biochem Biophys Rep. 2024 Feb 26;38:101669. doi: 10.1016/j.bbrep.2024.101669. eCollection 2024 Jul.
Tenofovir, as nucleotide reverse transcriptase inhibitors (NRTIs), is used to prevent and cure HIV/AIDS. Ample evidence confirmed that the nephrotoxicity of tenofovir has been linked to mitochondrial dysfunction. It seems that transplantation with healthy mitochondria instead of damaged mitochondria may be a beneficial approach to therapy. Therefore, it decided to investigate the impact of mitotherapy on tenofovir against renal proximal tubular cells (RPTCs) toxicity by measurement of oxidative stress and cytotoxicity biomarkers and restoring of mitochondrial function on isolated mitochondria. EC of tenofovir was achieved at 40 μM following 2 h incubation in Earle's solution (pH = 7.4; 37 °C). Freshly isolated mitochondria (80 μg/ml) were added to damage RPTCs affected by tenofovir in treated groups. One Way ANOVA analysis showed that healthy mitochondrial transplantation decreased oxidative stress biomarkers following tenofovir toxicity in RPTCs. Our data revealed that mitotherapy makes cell survival possible in RPTCs affected by tenofovir. In addition, it supposed that a novel and ideal strategy for the treatment of chemicals-induced nephrotoxicity.
替诺福韦作为核苷酸逆转录酶抑制剂（NRTIs），用于预防和治疗艾滋病毒/艾滋病。大量证据证实，替诺福韦的肾毒性与线粒体功能障碍有关。用健康的线粒体替代受损的线粒体进行移植似乎可能是一种有益的治疗方法。因此，决定通过测量氧化应激和细胞毒性生物标志物以及恢复分离线粒体的线粒体功能，研究线粒体疗法对替诺福韦抗肾近端小管细胞（RPTCs）毒性的影响。在Earle's溶液（pH = 7.4；37°C）中孵育2小时后，替诺福韦的半数效应浓度（EC）达到40μM。将新鲜分离的线粒体（80μg/ml）添加到治疗组中受替诺福韦影响的受损RPTCs中。单因素方差分析表明，健康线粒体移植降低了替诺福韦对RPTCs毒性后的氧化应激生物标志物。我们的数据显示，线粒体疗法使受替诺福韦影响的RPTCs中的细胞存活成为可能。此外，推测这是一种治疗化学物质诱导的肾毒性的新颖且理想的策略。
