Low intensity pulsed ultrasound ameliorates Adriamycin-induced chronic renal injury by inhibiting ferroptosis

ABSTRACT

Objective

It is very important to develop a new therapeutic strategy to cope with the increasing morbidity and mortality of chronic kidney disease (CKD). As a kind of physical therapy, low intensity pulsed ultrasound (LIPUS) has remarkable anti-inflammatory and repair-promoting effects and is expected to become a new therapeutic method for CKD. This study aims to clarify the treatment effect of LIPUS on CKD-related renal inflammation and fibrosis, and to further explore the potential signal network of LIPUS treatment for ameliorating chronic renal injury.

Methods

A rat model simulating the progress of CKD was established by twice tail-vein injection of Adriamycin (ADR). Under anesthesia, bilateral kidneys of CKD rats were continuously stimulated by LIPUS for four weeks. The parameters of LIPUS were 1.0 MHz, 60 mW/cm², 50% duty cycle and 20 min/d.

Results

LIPUS treatment effectively inhibited ADR-induced renal inflammation and fibrosis, and improved CKD-related to oxidative stress and ferroptosis. In addition, the therapeutic effect of LIPUS is closely related to the regulation of TGF-β₁/Smad and Nrf2/keap1/HO-1 signalling pathways.

Discussion

This study provides a new direction for further mechanism research and lays an important foundation for clinical trials.

KEYWORDS:

• Chronic kidney disease
• Low intensity pulsed ultrasound
• Inflammation
• Fibrosis
• Oxidative stress
• Ferroptosis
• TGF-β₁/Smad pathway
• Nrf2/keap1/HO-1 pathway

Acknowledgements

Conceptualisation, C.-D.L. and L.H.; methodology, Z.-Q.OY., L.-S.S., W.-P.W. and D.C.; formal analysis, Z.-Q.OY., T.-F.K. and G.-R.Z.; investigation, Z.-Q.OY., X.-R.D., J.-X. C, Y.Z. L.Y. and H.-Y.S.; resources, C.-D.L. and L.H.; data curation, Z.-Q.OY., L.-S.S., and T.-F.K.; writing – original draft preparation, Z.-Q.OY.; writing – review and editing, C.-D.L. and L.H.; supervision, C.-D.L.; project administration, C.-D.L. and Z.-Q.OY.; funding acquisition, C.-D.L. and Z.-Q.OY.; All authors have read and agreed to the published version of the manuscript.

Disclosure statement

No potential conflict of interest was reported by the author(s).

Availability of data and material

The authors declare that data supporting the findings of this study are available within the article.

Additional information

Funding

This work was supported by Yunnan Talents Support Program [grant number XDYC-MY-2022-0064]; National Natural Science Foundation of China [grant number 82160340]; Innovation Fund for Doctoral Students of Kunming Medical University [grant unmber 2023B012].