β-Hydroxybutyrate exacerbates lipopolysaccharide/ d-galactosamine-induced inflammatory response and hepatocyte apoptosis in mice.

Abstract

β-Hydroxybutyrate (BHB), one of ketone body, has been traditionally regarded as an alternative carrier of energy, but recent studies found that BHB plays versatile roles in inflammation. It has been previously reported that the level BHB declined in mice with lipopolysaccharide (LPS)/d-galactosamine (d-Gal)-induced liver damage, but the pathological significance remains unclear. In the present study, the pathophysiological roles of BHB in LPS/d-Gal-induced hepatic damage has been investigated. The results indicated pretreatment with BHB further enhanced LPS/d-Gal-induced elevation of aspartate aminotransferase and alanine aminotransferase, exacerbated the histological abnormalities and increased the mortality. Pretreatment with BHB upregulated the level of tumor necrosis factor α and interleukin-6 in plasma, promoted the activities of caspase-3, caspase-8, and caspase-9 and increased the count of terminal deoxynucleotidyl transferase dUTP nick end labeling-positive cells. In addition, post-insult supplement with BHB also potentiated LPS/d-Gal-induced apoptotic liver damage. Therefore, BHB might be a detrimental factor in LPS/d-Gal-induced liver injury via enhancing the inflammation and the apoptosis in the liver.