Evaluation of Endothelial Dysfunction and Autophagy in Fibromyalgia-Related Vascular and Cerebral Cortical Changes and the Ameliorative Effect of Fisetin

Abstract

Fibromyalgia (FM) is a common chronic pain syndrome that affects 1% to 5% of the population. We aimed to investigate the role of endothelial dysfunction and autophagy in fibromyalgia-related vascular and cerebral cortical changes in a reserpine-induced rat model of fibromyalgia at the histological and molecular levels and to study the ameliorative effect of fisetin. Forty adult female albino rats were divided into four groups (10 each): two control groups, the reserpine-induced fibromyalgia group, and the fisetin-treated group. The carotid arteries and brains of the animals were dissected. Frozen tissue samples were used for total RNA extraction and qPCR analysis of eNOS, caspase-3, Bcl-2, LC-3, BECN-1, CHOP, and TNF-α expression. Histological, immunohistochemical (eNOS), and ultrastructure studies were conducted. The carotid arteries revealed excessive autophagy and endothelial, vascular, and apoptotic changes. The cerebral cortex showed similar findings apart from endoplasmic reticulum stress. Additionally, there was decreased gene expression of eNOS and Bcl-2 and increased expression of caspase-3, LC-3, BECN-1, CHOP, and TNF-α. In the fisetin-treated rats, improvements in the histological and molecular results were detected. In conclusion, oxidative stress, enhanced apoptosis, and excessive autophagy are fundamental pathophysiologic mechanisms of reserpine-induced fibromyalgia. Moreover, fisetin has an ameliorative effect against fibromyalgia.

Neuroprotective effects of flavonoids: endoplasmic reticulum as the target

“…Fisetin (7,3′,4′- flavon-3-ol) is a flavonoid with antioxidant and anti-inflammatory qualities. In a reserpine-induced model of fibromyalgia, Ghoneim et al (2021) explored the possible impacts of Fisetin. When the carotid artery and cerebral cortex of subjects within the control group were inspected, a high level of autophagy markers, light chain 3 (LC-3) and Beclin-1 (BECN-1), and apoptosis was found within the carotids as well as endothelial, vascular and cerebral cortex evidenced by a significant rise in caspase-3 expression and reduced Bcl-2 mRNA gene expression.…”