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Maintenance of Carnitine Homeostasis as a Therapeutic Strategy to Attenuate Cisplatin‐Induced Acute Kidney Injury

Year: 2025

Type: article

Abstract: ABSTRACT Acute kidney injury (AKI) has emerged as a significant global public health concern due to its high morbidity and mortality rates. Cisplatin, a highly effective and widely used chemotherapeutic agent, is often limited in clinical application by its nephrotoxicity, particularly AKI. This study aimed to elucidate the mechanisms underlying cisplatin‐induced nephrotoxicity through multi‐omics approaches and to explore potential therapeutic strategies. Serum‐targeted metabolomics revealed a significant reduction in circulating l ‐carnitine and acylcarnitine levels following cisplatin administration. Renal proteomics showed marked downregulation of carnitine/organic cation transporter 2 (OCTN2), while renal lipid metabolomics demonstrated accumulation of medium‐ and long‐chain fatty acids in the kidney. Furthermore, renal fatty acid oxidation (FAO) activity, as measured by ELISA, was significantly decreased. Given the critical role of OCTN2 in renal l ‐carnitine reabsorption and FAO regulation, we investigated whether l ‐carnitine supplementation could alleviate cisplatin‐induced nephrotoxicity. Our findings indicate that cisplatin significantly suppresses OCTN2 expression, thereby disrupting carnitine homeostasis, impairing mitochondrial FAO, destabilizing mitochondrial dynamics, and ultimately inducing apoptosis. In contrast, l ‐carnitine supplementation restored OCTN2 expression, enhanced FAO, activated the AMPK/PGC‐1α/Sirt3 signaling pathway, and attenuated oxidative stress and apoptosis. In conclusion, l ‐carnitine exhibits significant therapeutic potential against cisplatin‐induced nephrotoxicity by modulating multiple targets related to FAO and mitochondrial dynamics.

Source: Food Frontiers

DOI: 10.1002/fft2.70178

Authors: Mingkang Zhang, Yazhi Wang, Xiujuan Wang, Yan Zhou, Yanrong Ma, Xin'an Wu

Institutions: First Hospital of Lanzhou University, Lanzhou University

Language: English

Topic: Chemotherapy-induced organ toxicity mitigation

Subfield: Pathology and Forensic Medicine

Field: Medicine

Domain: Health Sciences

SDG: Good health and well-being

Open Access status: gold

Estimated APC paid: $3,700