Abstract
Novel treatment strategies are urgently required for osteoarthritis (OA). Palmitoylethanolamide (PEA) is a naturally occurring fatty acid amide with analgesic and anti-inflammatory effects. We aimed to examine its effect on OA and elucidate the molecular mechanism of actions in monosodium iodoacetate (MIA)-induced OA Sprague–Dawley rats. The experimental animals were divided into normal control group (injected with saline + treated with phosphate-buffered saline (PBS), NOR), control group (injected with MIA + treated with PBS, CON), 50 or 100 mg/kg body weight (BW)/day PEA-treated group (injected with MIA + treated with 50 or 100 mg of PEA/kg BW/day, PEA50 or PEA100), and positive control group (injected with MIA + treated with 6 mg of diclofenac/kg BW/day, DiC). The changes in blood parameters, body parameters, gene expression of inflammatory mediators and cytokines, knee thickness, and joint tissue were observed. Oral administration of PEA had no adverse effects on the BW, liver, or kidneys. PEA reduced knee joint swelling and cartilage degradation in MIA-induced OA rats. The serum levels of leukotriene B4, nitric oxide, tumor necrosis factor (TNF)-α, interleukin (IL)-1β, and prostaglandin E2 considerably reduced in the PEA100 group compared with those in the CON group. In the synovia of knee joints, the mRNA expression of iNOS, 5-Lox, Cox-2, Il-1β, Tnf-α, and Mmp-2, -3, -9, and -13 apparently increased with MIA administration. Meanwhile, Timp-1 mRNA expression apparently decreased in the CON group but increased to the normal level with PEA treatment. Thus, PEA can be an effective therapeutic agent for OA.
Highlights
Osteoarthritis (OA) is a common progressive and degenerative joint disease that arises from joint cartilage destruction and joint tissue repair induced by inflammatory mediators (Alshami 2014; Steels et al 2019)
Enzyme-linked immunosorbent assay (ELISA) kits for prostaglandin E2 ( PGE2), leukotriene B4 ( LTB4), tumor necrosis factor-α (TNF)-α, and interleukin (IL)-1β were purchased from R&D Systems (Minneapolis, MN, USA)
We measured the body weight (BW) of the rats during the experimental period and conducted a blood biochemical analysis to determine whether PEA administration caused adverse effects in vivo
Summary
Osteoarthritis (OA) is a common progressive and degenerative joint disease that arises from joint cartilage destruction and joint tissue repair induced by inflammatory mediators (Alshami 2014; Steels et al 2019). As the cause of OA is unclear, its management is limited to medications to relieve pain, exercise therapy, weight control, prevention of complications such as muscle degeneration and joint deformity, and maintenance of the range of motion of the joint (Mora et al 2018). It was reported that neuroinflammation caused by an imbalance between pro-inflammatory and pro-resolving mediators plays an important role in pain progression (Paladini et al 2016). Due to a natural immune response is observed in patients with OA (Chen et al 2017; Mora et al 2018). Long-term medications can alleviate OA pain but not cure OA (Bjordal et al 2007)
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