SS-31 prevented cisplatin-induced acute kidney injury in mice by suppressing mitochondrial ROS and downregulating the NLRP3 inflammasome pathway, protecting kidney cells from apoptosis.
10 mg/kg/daySS-31 dose that protected mouse kidneys from cisplatin damage over 10 days
What the researchers found
SS-31 treatment suppressed mitochondrial ROS, ameliorated kidney lesions, and decreased NLRP3, IL-1β, and caspase-1 expression in both cisplatin-treated mice and HK-2 kidney cells, protecting against acute kidney injury.
Why it matters
Cisplatin-induced kidney injury is a major clinical problem limiting chemotherapy dosing. SS-31 (elamipretide) is already in clinical trials for other mitochondrial conditions, making this a potential near-term therapeutic option for kidney protection during chemotherapy.
The numbers in context
32 mice; SS-31 10 mg/kg/day x 10 days; cisplatin 25 mg/kg IP; significant reduction in kidney damage, oxidative stress, and NLRP3 activation.
How the study worked
In vivo: 32 C57BL/6 mice in 4 groups, cisplatin (25 mg/kg single injection), SS-31 (10 mg/kg/day for 10 days). Measured creatinine, BUN, histology, electron microscopy. In vitro: HK-2 cells with cisplatin (50 μM) ± SS-31 (100 μM). Measured mitochondrial ROS, apoptosis, NLRP3 pathway proteins.
Who was studied
C57BL/6 mice with cisplatin-induced acute kidney injury and HK-2 kidney cells
What this study cannot tell us
Single cisplatin dose model may not replicate cumulative kidney damage from repeated chemotherapy cycles. Mouse-to-human dose translation uncertain. SS-31 has not been tested for this indication in human trials.
How to read the evidence
Solid preclinical evidence with both in vivo (32 mice) and in vitro confirmation. Clear mechanistic pathway identified but no human data for this indication.
When this study was published
Published in 2020. SS-31/elamipretide has continued to advance in clinical trials for mitochondrial conditions.
The bigger picture
SS-31/elamipretide is emerging as a versatile mitochondrial protectant across multiple organ systems. This study adds chemotherapy-induced kidney injury to its potential applications, building on its existing clinical development for heart and eye conditions.
Questions still open
- Would SS-31 protect kidneys during repeated chemotherapy cycles without reducing anti-cancer efficacy?
- How does SS-31's nephroprotective effect compare to existing strategies like hydration and amifostine?
- Could SS-31 be combined with other nephroprotective agents for enhanced kidney protection?
Common questions
What is SS-31 (elamipretide)?
Why does chemotherapy damage kidneys?
Read the original research
Mitochondria targeted peptide SS-31 prevent on cisplatin-induced acute kidney injury via regulating mitochondrial ROS-NLRP3 pathway.
Biomedicine & pharmacotherapy = Biomedecine & pharmacotherapie, 130, 110521
Citation
Yang, Shi-Kun; Han, Ya-Chun; He, Jin-Rong; Yang, Ming; Zhang, Wei; Zhan, Ming; Li, Ai-Mei; Li, Liu; Na-Song; Liu, Yu-Ting; Wu, Xue-Qin; Zhang, Qin; Wang, Jian-Wen; Zhang, Hao. (2020). Mitochondria targeted peptide SS-31 prevent on cisplatin-induced acute kidney injury via regulating mitochondrial ROS-NLRP3 pathway.. Biomedicine & pharmacotherapy = Biomedecine & pharmacotherapie, 130, 110521. https://doi.org/10.1016/j.biopha.2020.110521