Melatonin prevents bone loss in osteoporotic rats with valproic acid treatment by anti-inflammatory and anti-oxidative stress

Int Immunopharmacol. 2024 Nov 15:141:112932. doi: 10.1016/j.intimp.2024.112932. Epub 2024 Aug 17.

Abstract

Melatonin (MEL) has shown positive effects in anti-inflammatory and anti-oxidative stress research. This study investigates whether MEL can positively impact bone loss induced by valproic acid (VPA) in rats. The study examines changes in MC3T3-E1 cell viability and osteogenic potential, along with osteoclast differentiation in RAW264.7 cells in the presence of VPA using CCK-8, ALP staining, AR staining, and TRAP staining. In vitro experiments reveal that VPA-induced inhibition of osteogenic differentiation and promotion of osteoclastic differentiation are linked to increased inflammation and oxidative stress. Furthermore, MEL has demonstrated the ability to reduce oxidative stress and inflammation, boost osteogenic differentiation, and inhibit osteoclast differentiation. Animal experiments confirm that MEL significantly increases SOD2 expression and decreases TNF-α expression, leading to the restoration of impaired bone metabolism, enhanced bone strength, and higher bone mineral density. The combined experimental results strongly suggest that MEL can enhance osteogenic activity in the presence of VPA by reducing inflammation and oxidative stress, impeding osteoclast differentiation, and alleviating bone loss in VPA-treated rat models.

Keywords: Bone mass; Inflammation; Melatonin; Oidative stress; Valproic acid.

MeSH terms

  • Animals
  • Anti-Inflammatory Agents* / pharmacology
  • Anti-Inflammatory Agents* / therapeutic use
  • Antioxidants / pharmacology
  • Antioxidants / therapeutic use
  • Bone Density / drug effects
  • Cell Differentiation* / drug effects
  • Female
  • Melatonin* / pharmacology
  • Melatonin* / therapeutic use
  • Mice
  • Osteoblasts / drug effects
  • Osteoblasts / metabolism
  • Osteoclasts* / drug effects
  • Osteogenesis* / drug effects
  • Osteoporosis* / drug therapy
  • Oxidative Stress* / drug effects
  • RAW 264.7 Cells
  • Rats
  • Rats, Sprague-Dawley*
  • Superoxide Dismutase / metabolism
  • Tumor Necrosis Factor-alpha / metabolism
  • Valproic Acid* / pharmacology
  • Valproic Acid* / therapeutic use

Substances

  • Valproic Acid
  • Melatonin
  • Anti-Inflammatory Agents
  • Superoxide Dismutase
  • Tumor Necrosis Factor-alpha
  • Antioxidants
  • superoxide dismutase 2