Exploring the Roles of Vitamins C and D and Etifoxine in Combination with Citalopram in Depression/Anxiety Model: A Focus on ICAM-1, SIRT1 and Nitric Oxide

Int J Mol Sci. 2024 Feb 6;25(4):1960. doi: 10.3390/ijms25041960.

Abstract

The study of intercellular adhesion molecule-1 (ICAM-1) and SIRT1, a member of the sirtuin family with nitric oxide (NO), is emerging in depression and anxiety. As with all antidepressants, the efficacy is delayed and inconsistent. Ascorbic acid (AA) and vitamin D (D) showed antidepressant properties, while etifoxine (Etx), a GABAA agonist, alleviates anxiety symptoms. The present study aimed to investigate the potential augmentation of citalopram using AA, D and Etx and related the antidepressant effect to brain and serum ICAM-1, SIRT1 and NO in an animal model. BALB/c mice were divided into naive, control, citalopram, citalopram + etx, citalopram + AA, citalopram + D and citalopram + etx + AA + D for 7 days. On the 8th day, the mice were restrained for 8 h, followed by a forced swim test and marble burying test before scarification. Whole-brain and serum expression of ICAM-1, Sirt1 and NO were determined. Citalopram's antidepressant and sedative effects were potentiated by ascorbic acid, vitamin D and etifoxine alone and in combination (p < 0.05), as shown by the decreased floating time and rearing frequency. Brain NO increased significantly (p < 0.05) in depression and anxiety and was associated with an ICAM-1 increase versus naive (p < 0.05) and a Sirt1 decrease (p < 0.05) versus naive. Both ICAM-1 and Sirt1 were modulated by antidepressants through a non-NO-dependent pathway. Serum NO expression was unrelated to serum ICAM-1 and Sirt1. Brain ICAM-1, Sirt1 and NO are implicated in depression and are modulated by antidepressants.

Keywords: ICAM-1; SIRT1; citalopram; depression.

MeSH terms

  • Animals
  • Antidepressive Agents / pharmacology
  • Antidepressive Agents / therapeutic use
  • Anxiety* / drug therapy
  • Ascorbic Acid / pharmacology
  • Ascorbic Acid / therapeutic use
  • Citalopram* / pharmacology
  • Citalopram* / therapeutic use
  • Depression* / drug therapy
  • Drug Therapy, Combination
  • Intercellular Adhesion Molecule-1
  • Mice
  • Nitric Oxide*
  • Oxazines* / pharmacology
  • Oxazines* / therapeutic use
  • Sirtuin 1
  • Vitamin D / pharmacology
  • Vitamin D / therapeutic use
  • Vitamins

Substances

  • Antidepressive Agents
  • Ascorbic Acid
  • Citalopram
  • etifoxine
  • Intercellular Adhesion Molecule-1
  • Nitric Oxide
  • Oxazines
  • Sirtuin 1
  • Vitamin D
  • Vitamins

Grants and funding

This research was funded by Yarmouk University, grant number “51/2022”.