Sodium thiosulfate through preserving mitochondrial dynamics ameliorates oxidative stress induced renal apoptosis and ferroptosis in 5/6 nephrectomized rats with chronic kidney diseases

Yu Hsuan Cheng, Chien An Yao, Chih Ching Yang, Shih Ping Hsu*, Chiang Ting Chien*

*此作品的通信作者

研究成果: 雜誌貢獻期刊論文同行評審

1 引文 斯高帕斯(Scopus)

摘要

Chronic kidney disease (CKD) progression may be evoked through dysregulated mitochondrial dynamics enhanced oxidative stress and inflammation contributing to high cardiovascular morbidity and mortality. Previous study has demonstrated sodium thiosulfate (STS, Na2S2O3) could effectively attenuate renal oxidative injury in the animal model of renovascular hypertension. We explored whether the potentially therapeutic effect of STS is available on the attenuating CKD injury in thirty-six male Wistar rats with 5/6 nephrectomy. We determined the STS effect on reactive oxygen species (ROS) amount in vitro and in vivo by an ultrasensitive chemiluminescence-amplification method, ED-1 mediated inflammation, Masson’s trichrome stained fibrosis, mitochondrial dynamics (fission and fusion) and two types of programmed cell death, apoptosis and ferroptosis by western blot and immunohistochemistry. Our in vitro data showed STS displayed the strongest scavenging ROS activity at the dosage of 0.1 g. We applied STS at 0.1 g/kg intraperitoneally 5 times/week for 4 weeks to these CKD rats. CKD significantly enhanced the degree in arterial blood pressure, urinary protein, BUN, creatinine, blood and kidney ROS amount, leukocytes infiltration, renal 4-HNE expression, fibrosis, dynamin-related protein 1 (Drp1) mediated mitochondrial fission, Bax/c-caspase 9/c-caspase 3/poly (ADP-ribose) polymerase (PARP) mediated apoptosis, iron overload/ferroptosis and the decreased xCT/GPX4 expression and OPA-1 mediated mitochondrial fusion. STS treatment significantly ameliorated oxidative stress, leukocyte infiltration, fibrosis, apoptosis and ferroptosis and improved mitochondrial dynamics and renal dysfunction in CKD rats. Our results suggest that STS as drug repurposing strategy could attenuate CKD injury through the action of anti-mitochondrial fission, anti-inflammation, anti-fibrosis, anti-apoptotic, and anti-ferroptotic mechanisms.

原文英語
文章編號e0277652
期刊PloS one
18
發行號2 February
DOIs
出版狀態已發佈 - 2023 2月

ASJC Scopus subject areas

  • 多學科

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