Ameliorative effect of nano-pregabalin in gastrocnemius muscle of gamma irradiated rats with an experimental model of fibromyalgia: Crosstalk of Sirt3, IL-1β and PARP1 pathways

Toxicol Appl Pharmacol. 2024 Sep:490:117037. doi: 10.1016/j.taap.2024.117037. Epub 2024 Jul 14.

Abstract

Background: Fibromyalgia (FM) is a complex syndrome with somatic symptoms connected to the operational state of muscles. Although radiotherapy is a cornerstone in cancer treatment, it is implicated in the aggravation of FM. Lately, formulation of medicines in nano-forms become of great prominence due to their prospective applications in medicine. So, this study aimed to assess possible therapeutic benefits of formulating pregabalin in a nono-form (N-PG) for managing FM during exposure to gamma radiation.

Methods: Gamma rays administered in fractionated doses (2 Gy/day) to male rats after one hour of s.c. injection of reserpine (1 mL/kg per day) to induce FM, then treated with single daily dose of (30 mg/kg, p.o.) PG or N-PG for ten successive days. Rats were subjected to behavioral tests, then sacrificed to obtain serum and gastrocnemius muscles.

Results: N-PG significantly antagonized reserpine-induced FM as proved by; the immobility and performance times in forced swim and rotarod performance tests, respectively were restored near to the normal time, serum IL-8 and MCP-1 chemokines were nearby the normal levels, mitigated oxidative stress through increasing total thiol, Sirt3, CAT enzyme and decreasing COX-1, inhibition of inflammation via IL-1β and MIF significant reduction, it possessed anti-apoptotic effect verified by decreasing PARP-1 and increasing Bcl-XL, gastrocnemius muscles had minimal fibrosis levels as seen after Masson trichrome staining. Histopathological results were coincidence with biochemical inspection.

Conclusion: This study identifies N-PG as a novel drug that could be of a value in the management of FM particularly in cancer patients undergoing radiotherapy.

Keywords: Behavioral examinations; Fibromyalgia; Gastrocnemius muscle; Nanomedecines; Pregabalin; Radiotherapy.

MeSH terms

  • Animals
  • Disease Models, Animal
  • Fibromyalgia* / drug therapy
  • Gamma Rays*
  • Interleukin-1beta* / metabolism
  • Male
  • Muscle, Skeletal* / drug effects
  • Muscle, Skeletal* / metabolism
  • Muscle, Skeletal* / pathology
  • Muscle, Skeletal* / radiation effects
  • Nanoparticles
  • Oxidative Stress / drug effects
  • Poly (ADP-Ribose) Polymerase-1 / metabolism
  • Rats
  • Rats, Wistar*
  • Signal Transduction / drug effects

Substances

  • Interleukin-1beta
  • Poly (ADP-Ribose) Polymerase-1
  • IL1B protein, rat