β-hydroxybutyrate suppresses pathological changes of blood-induced arthropathy in rats

Sci Rep. 2024 Nov 29;14(1):29696. doi: 10.1038/s41598-024-77074-6.

Abstract

Arthropathy is a common complication in haemophilia and decreases quality of life. It has been known that concentrations of β-hydroxybutyrate (BHB) in blood are increased by a ketogenic diet, and elevated levels of circulating BHB restricts the progression of inflammation-mediated joint pathological changes. We hypothesized that elevation of blood BHB concentrations could be effective for reducing the progression of bleeding-induced arthropathy by moderating the inflammatory responses of macrophages. In this study, we investigated whether BHB alleviates the arthropathy caused by repeated intra-articular blood injection in rats. To increase blood BHB levels, rats were fed with ketogenic diet. Repeated intra-articular blood injection induced significant joint swelling, whereas ketogenic diet intake significantly increased blood BHB concentrations and ameliorated the joint swelling. The periarticular tissue-fibrosis observed in the control diet intake group appeared to be significantly alleviated in the ketogenic diet intake group. In addition, the IL-1β, which is involved in the progression of arthropathy, levels in the supernatants of blood-exposed macrophages derived from THP-1 cell line were significantly suppressed by BHB supplementation. In summary, BHB moderated the pathological joint changes caused by intra-articular blood exposure.

MeSH terms

  • 3-Hydroxybutyric Acid* / blood
  • 3-Hydroxybutyric Acid* / pharmacology
  • Animals
  • Diet, Ketogenic*
  • Disease Models, Animal
  • Humans
  • Injections, Intra-Articular
  • Interleukin-1beta / blood
  • Interleukin-1beta / metabolism
  • Joint Diseases / drug therapy
  • Joint Diseases / etiology
  • Joint Diseases / pathology
  • Macrophages / drug effects
  • Macrophages / metabolism
  • Male
  • Rats
  • Rats, Sprague-Dawley
  • THP-1 Cells

Substances

  • 3-Hydroxybutyric Acid
  • Interleukin-1beta