Attenuation of reserpine‑induced fibromyalgia via ROS and serotonergic pathway modulation by fisetin, a plant flavonoid polyphenol

Abstract

Fibromyalgia (FM) is a chronic complex musculoskeletal disorder characterized by widespread musculoskeletal pain accompanied by fatigue, sleep disturbance, memory defects and mood changes. Fisetin, a plant flavonoid polyphenol, has been reported to possess potent antioxidant, antinociceptive and neuroprotective activities. The present study aimed to evaluate the efficacy of fisetin against reserpine-induced FM (RIF) in rats. RIF was induced in male Wistar rats (180-220 gm) using reserpine (1 mg/kg; subcutaneous; once daily for 3 consecutive days) and the rats were treated with fisetin (5, 10 and 25 mg/kg) for 21 days. Various behavioral, biochemical and molecular parameters were evaluated. Administration of reserpine induced allodynia, hyperalgesia and depression, which were significantly ameliorated (P<0.05) by fisetin (10 and 25 mg/kg), as reflected by an increase in paw and tail withdrawal latency, increased paw withdrawal threshold, and decreased immobility time. Reserpine led to decreased biogenic amine levels [5-hydroxytryptamine (5-HT), noradrenaline (NA) and dopamine (DA)] and increased the ratio to their metabolite 3,4-dihydroxyphenylacetic acid. 5-hydroxyindoleacetic acid in the spinal cord, thalamus and prefrontal cortex was significantly decreased (P<0.05) by fisetin. Immunohistological analysis of brain tissue revealed that fisetin significantly inhibited (P<0.05) reserpine-induced depletion of 5-HT. It also significantly inhibited (P<0.05) elevated oxido-nitrosative stress and reactive oxygen species (ROS) levels, as analyzed by flow cytometry in RIF rats. Fisetin exerts its antinociceptive and anti-depressive potential via modulation of decreased levels of biogenic amines (5-HT, NA and DA), elevated oxido-nitrosative stress and ROS to ameliorate allodynia, hyperalgesia, and depression in experimental RIF.

Kinin B1 receptor is involved in mechanical nociception in a fibromyalgia-like model in mice

“…This is different from the study of Brusco and collaborators, who decided to use a high dose (1 mg/kg) of reserpine in the same schedule of treatment. In our previous work (11) , reserpine (0.25 mg/kg) impaired locomotor activity, assayed in an open field arena, which is corroborated by other studies (24)(25)(26) . Such locomotor impairment induced by reserpine was not observed by Brusco and collaborators (12) , and was also not reported in other publications (27) .…”

Piceatannol promotes hepatic and renal AMPK/SIRT1/PGC-1α mitochondrial pathway in rats exposed to reserpine or gamma-radiation

“…Following its systemic administration, reserpine is distributed to tissues based on their blood flow and easily penetrate cell membranes and then bind to the intracellular membrane components, particularly those rich in phospholipids, forming adducts inducing a nonstoichiometric inhibition of monoamine uptake, 40 with a consequent oxidative stress status due to the oxidation processes of those monoamines by monoamine oxidases. 41 Also, accumulation of tissue lipid peroxides induces an inflammatory status interfering with the mitochondrial functions in multiple organs including the liver and kidney.…”

D-Pinitol Protected Against Endoplasmic Reticulum Stress and Apoptosis in Hepatic Ischemia-Reperfusion Injury Via Modulation of AFT4-CHOP/GRP78 and Caspase-3 Signaling Pathways

“…Furthermore, the elevated production of free radical during IRI increases lipid peroxidation levels, which causes signi cant cellular damage [14]. Malonaldehyde is considered an important measure for lipid peroxidase induced cellular damage [45][46][47]. During IRI, the rst line cellular defense system is impaired, resulting in hydrogen peroxide generation, divided into free radicals viz., hydrogen, and oxygen, which further damages the number of biological moieties, including proteins, amino acids, and nucleic acids [48][49][50].…”