The Anti-Inflammatory and Pain-Relieving Effects of AR170, an Adenosine A3 Receptor Agonist, in a Rat Model of Colitis

Abstract

The pharmacological activation of A3 receptors has shown potential usefulness in the management of bowel inflammation. However, the role of these receptors in the control of visceral hypersensitivity in the presence of intestinal inflammation has not been investigated. The effects of AR170, a potent and selective A3 receptor agonist, and dexamethasone (DEX) were tested in rats with 2,4-dinitrobenzene sulfonic acid (DNBS)-induced colitis to assess their tissue inflammatory parameters. The animals received AR170, DEX, or a vehicle intraperitoneally for 6 days, starting 1 day before the induction of colitis. Visceral pain was assessed by recording the abdominal responses to colorectal distension in animals with colitis. Colitis was associated with a decrease in body weight and an increase in spleen weight. The macroscopic damage score and tissue tumor necrosis factor (TNF), interleukin 1β (IL-1β), and myeloperoxidase (MPO) levels were also enhanced. AR170, but not DEX, improved body weight. Both drugs counteracted the increase in spleen weight, ameliorated macroscopic colonic damage, and decreased TNF, IL-1β, and MPO tissue levels. The enhanced visceromotor response (VMR) in rats with colitis was decreased via AR170 administration. In rats with colitis, AR170 counteracted colonic inflammatory cell infiltration and decreased pro-inflammatory cytokine levels, thereby relieving visceral hypersensitivity.

Targeting Adenosine Receptors: A Potential Pharmacological Avenue for Acute and Chronic Pain

“…AL170 mitigates the colonic damage and inflammation, reducing the release of TNF-α, IL-1β, and myeloperoxidase. AL170 was demonstrated to have an efficacy comparable to that of dexamethasone, one of the most used drugs in the colitis treatment and other inflammatory bowel diseases [ 131 ]. The activation of A 3 ARs resulted able to decrease the infiltration of inflammatory cells and the production of inflammatory mediators thus softening visceral pain [ 131 ].…”

“…AL170 was demonstrated to have an efficacy comparable to that of dexamethasone, one of the most used drugs in the colitis treatment and other inflammatory bowel diseases [ 131 ]. The activation of A 3 ARs resulted able to decrease the infiltration of inflammatory cells and the production of inflammatory mediators thus softening visceral pain [ 131 ]. A further study revealed that the treatment with A 3 AR agonists is useful in another model of abdominal pain induced by colitis.…”

Protective potential of piroxicam on human peripheral blood mononuclear cells against suppressive capacity of U-87 MG cell line

“…Dexamethasone, widely known as an anti-in ammatory medication (23,24), is expedient to decline chemotherapy side effects as well as the neurological symptoms in patients with brain cancers (23). However, due to the suppressive properties of dexamethasone especially on the anti-tumor T-cell responses (25), identifying a competent alternative seems necessary.…”

Adenosine Targeting as a New Strategy to Decrease Glioblastoma Aggressiveness

“…An important aspect of the mechanism of escape by the tumor from the immune system is the TME [ 106 ], which is characterized by a hypoxic state and is rich in inhibitory ligands and cytokines, such as IL-10 and TGF-β, which lead to tolerance by the immune cells towards the tumor [ 107 , 108 ] ( Figure 3 ). These conditions determine the increase in the expression of CD39 and CD73 [ 89 ], present on the surface of the tumor by stimulating the production of extracellular adenosine, by activating A2AAR.…”