# Renoprotective effects of human L-type fatty acid-binding protein (hL-FABP) in rhabdomyolysis-induced acute kidney injury

## TL;DR

This study shows that human L-type fatty acid-binding protein in the kidneys can protect against acute kidney injury caused by muscle breakdown.

## Contribution

The study demonstrates that hL-FABP mitigates rhabdomyolysis-induced AKI through antioxidative effects and inhibition of ferroptosis.

## Key findings

- Tg-RM mice showed improved renal function and reduced tubulointerstitial damage compared to WT-RM mice by day 3.
- hL-FABP suppressed lipid peroxidation and ferroptosis markers in Tg-RM mice.
- Renal hL-FABP may prevent progression of RM-induced AKI through antioxidative effects.

## Abstract

L-type fatty acid-binding protein (L-FABP) in proximal tubules is reported to reduce oxidative stress. This study investigated whether renal L-FABP mitigated rhabdomyolysis (RM)-induced acute kidney injury (AKI). Wild-type (WT) mice, which lack renal L-FABP expression, and human L-FABP (hL-FABP) chromosomal transgenic (Tg) mice, which express hL-FABP in proximal tubules, were divided into RM (WT-RM, Tg-RM) and control (WT-Cont, Tg-Cont) groups. RM was induced via intramuscular injection of 50% glycerol/PBS into the quadriceps, whereas controls received PBS alone. On day 1, the WT-RM and Tg-RM groups exhibited similar increases in serum myoglobin, renal dysfunction, heme oxygenase-1 expression, and tubulointerstitial damage. By day 3, the Tg-RM group demonstrated significant improvements in renal function, attenuation of tubulointerstitial damage, and decrease in macrophage infiltration compared with the WT-RM group. Lipid peroxidation marker 4-hydroxynonenal increased similarly in both RM groups on day 1, but its further elevation on day 3 was significantly suppressed in Tg-RM mice. Solute carrier family 7 member 11 on day 1 and glutathione peroxidase 4 on day 3 were significantly higher in Tg-RM mice than in WT-RM mice, which led to the suppression of ferroptosis. In conclusion, renal hL-FABP may prevent progression of RM-induced AKI through ferroptosis inhibition by antioxidative effects.

The online version contains supplementary material available at 10.1038/s41598-025-34045-9.