BACKGROUND: The present study was designed to investigate the protective effects and mechanisms of carnosine on lipopolysaccharide (LPS)-induced injury in Caenorhabditis elegans. METHODS: C. elegans individuals were stimulated for 24h with LPS (100g/mL), with or without carnosine (0.1, 1, 10mM). The survival rates and behaviors were determined. The activities of superoxide dismutase (SOD), glutathione reductase (GR), and catalase (CAT) and levels of malondialdehyde (MDA) and glutathione (GSH) were determined using the respective kits. Reverse transcription polymerase chain reaction (RT-PCR) was performed to validate the differential expression of
sod-1,
sod-2,
sod-3,
daf-16,
ced-3,
ced-9,
sek-1, and
pmk-1. Western blotting was used to determine the levels of SEK1,
p38 mitogen-activated protein kinase (MAPK), cleaved caspase3, and Bcl-2. C. elegans
sek-1 (
km2) mutants and
pmk-1 (
km25) mutants were used to elucidate the role of the
p38 MAPK signaling pathway. RESULTS: Carnosine improved the survival of LPS-treated C. elegans and rescued behavioral phenotypes. It also restrained oxidative stress by decreasing MDA levels and increasing SOD, GR, CAT, and GSH levels. RT-PCR results showed that carnosine treatment of wild-type C. elegans up-regulated the mRNA expression of the antioxidant-related genes
sod-1,
sod-2,
sod-3, and
daf-16. The expression of the anti-apoptosis-related gene
ced-9 and apoptosis-related gene
ced-3 was reversed by carnosine. In addition, carnosine treatment significantly decreased cleaved caspase3 levels and increased Bcl-2 levels in LPS-treated C. elegans. Apoptosis in the loss-of-function strains of the
p38 MAPK signaling pathway was suppressed under LPS stress; however, the apoptotic effects of LPS were blocked in the
sek-1 and
pmk-1 mutants. The expression levels of
sek-1 and
pmk-1 mRNAs were up-regulated by LPS and reversed by carnosine. Finally, the expression of p-
p38MAPK and SEK1 was significantly increased by LPS, which was reversed by carnosine. CONCLUSION: Carnosine treatment protected against LPS injury by decreasing oxidative stress and inhibiting apoptosis through the
p38 MAPK pathway.