Mitochondrial Peptide SS-31 Protects Kidneys from Chemotherapy Damage by Reducing Oxidative Stress

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.

Yang, Shi-Kun et al.·Biomedicine & pharmacotherapy = Biomedecine & pharmacotherapie·2020·Moderate Evidenceanimal
RPEP-05216AnimalModerate Evidence2020RETHINKTHC RESEARCH DATABASErethinkthc.com/research

Quick Facts

Study Type
animal
Evidence
Moderate Evidence
Sample
N=32 mice (8 per group) plus HK-2 cell experiments
Participants
C57BL/6 mice with cisplatin-induced acute kidney injury and HK-2 kidney cells

What This Study 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.

Key Numbers

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 They Did This

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.

Why This Research 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 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.

What This Study Doesn't 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.

Questions This Raises

  • ?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?

Trust & Context

Key Stat:
10 mg/kg/day SS-31 dose that protected mouse kidneys from cisplatin damage over 10 days
Evidence Grade:
Solid preclinical evidence with both in vivo (32 mice) and in vitro confirmation. Clear mechanistic pathway identified but no human data for this indication.
Study Age:
Published in 2020. SS-31/elamipretide has continued to advance in clinical trials for mitochondrial conditions.
Original Title:
Mitochondria targeted peptide SS-31 prevent on cisplatin-induced acute kidney injury via regulating mitochondrial ROS-NLRP3 pathway.
Published In:
Biomedicine & pharmacotherapy = Biomedecine & pharmacotherapie, 130, 110521 (2020)
Database ID:
RPEP-05216

Evidence Hierarchy

Meta-Analysis / Systematic Review
Randomized Controlled Trial
Cohort / Case-Control
Cross-Sectional / ObservationalSnapshot without intervening
This study
Case Report / Animal Study
What do these levels mean? →

Frequently Asked Questions

What is SS-31 (elamipretide)?

SS-31 is a small peptide that specifically targets the inner mitochondrial membrane, protecting these cellular powerhouses from oxidative damage. It's in clinical trials for heart failure and eye diseases.

Why does chemotherapy damage kidneys?

Cisplatin accumulates in kidney cells and generates massive amounts of reactive oxygen species (ROS) in mitochondria, triggering inflammation and cell death that impairs kidney function.

Read More on RethinkPeptides

Cite This Study

RPEP-05216·https://rethinkpeptides.com/research/RPEP-05216

APA

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

MLA

Yang, Shi-Kun, et al. "Mitochondria targeted peptide SS-31 prevent on cisplatin-induced acute kidney injury via regulating mitochondrial ROS-NLRP3 pathway.." Biomedicine & pharmacotherapy = Biomedecine & pharmacotherapie, 2020. https://doi.org/10.1016/j.biopha.2020.110521

RethinkPeptides

RethinkPeptides Research Database. "Mitochondria targeted peptide SS-31 prevent on cisplatin-ind..." RPEP-05216. Retrieved from https://rethinkpeptides.com/research/yang-2020-mitochondria-targeted-peptide-ss31

Access the Original Study

Study data sourced from PubMed, a service of the U.S. National Library of Medicine, National Institutes of Health.

This study breakdown was produced by the RethinkPeptides research team. We analyze and report published research findings without making health recommendations. All interpretations are based solely on the published abstract and study data.