L-carnitine attenuates trastuzumab-induced changes in cardiac H9c2 cells

In a laboratory study of cardiac H9c2 cells, researchers found that adding L-carnitine attenuated several changes induced by trastuzumab, including reduced cell viability, lower expression of AMPK-α2 and CPT1B, and increased levels of troponin I, creatine kinase-MB, acetyl-CoA carboxylase-2 and malonyl-CoA. These findings provide a preliminary mechanistic indication of cellular protection, but the experiment does not establish that L-carnitine prevents trastuzumab-related cardiotoxicity in patients.

Trastuzumab exposure reduced H9c2 cell viability in a concentration-dependent manner, with a reported half-maximal inhibitory concentration, or IC50, of 1.21 micromolar. The researchers also tested L-carnitine at 5 millimolar. When the cells received the IC50 concentration of trastuzumab together with that concentration of L-carnitine, the combination produced the strongest reduction in measured cellular toxicity among the tested conditions. The supplied abstract does not provide the full set of treatment comparisons or detailed statistical analyses, so the size and significance of the effect cannot be assessed from the available report.

Biochemical measurements showed that trastuzumab elevated troponin I, creatine kinase-MB, acetyl-CoA carboxylase-2 and malonyl-CoA, while L-carnitine counteracted these increases. At the messenger-RNA level, trastuzumab reduced expression of AMPK-α2 and carnitine palmitoyltransferase-1B, abbreviated CPT1B. The combination of trastuzumab and L-carnitine counteracted those reductions. Trastuzumab also decreased ATP and ATG-5 levels, and the combination counteracted those decreases. These observations were obtained in a cultured-cell model and therefore characterize molecular and viability responses under experimental conditions rather than clinical outcomes.

Based on the measured results, the authors concluded that trastuzumab disturbed AMPK-α2 downstream signaling, reduced ATP production and interfered with autophagy-related measurements, while L-carnitine tempered these effects. The study was designed as a preliminary mechanistic investigation, not a clinical trial, and its authors emphasized that additional research is required. The evidence therefore supports the narrower conclusion that L-carnitine attenuated selected trastuzumab-associated changes in H9c2 cells; it does not show that supplementation would be safe or effective for protecting the human heart during trastuzumab treatment.

Subject of Research: L-carnitine attenuation of trastuzumab-induced AMPK, metabolic and viability changes in cardiac H9c2 cells

Article Title: Mechanistic attenuation by L-carnitine of trastuzumab-induced downregulation of adenosine monophosphate -activated protein kinase signal in cardiac H9c2 cells

Article References: Attia, Y. M., Osman, A.-M. M., Shash, E., Elgazzar, M., Sharaky, M., Alanazi, F. E., Sayed-Ahmed, M. M., & Karkeet, R. M. (2026). Mechanistic attenuation by L-carnitine of trastuzumab-induced downregulation of adenosine monophosphate -activated protein kinase signal in cardiac H9c2 cells. BMC Pharmacology and Toxicology, 27(1), Article 140. https://doi.org/10.1186/s40360-026-01235-8

Image Credits: AI Generated

DOI: 10.1186/s40360-026-01235-8

Keywords: L-carnitine, trastuzumab, cardiotoxicity, H9c2 cells, AMPK-α2, CPT1B, ATP, autophagy, cell viability, Mechanistic, attenuation, trastuzumab-induced