Nrf2 Activation May Reduce Joint Inflammation in Patients With Gout

Biomedicine & Pharmacology published a study that found that “pharmacologically activating Nrf2 [nuclear factor erythroid 2-related factor 2] alleviates gout pain, gait impairments, inflammation, and peripheral sensitization via Nrf2-dependent antioxidant mechanism.” The study aimed to determine whether pharmacologically activating Nrf2 using the oltipraz activator could attenuate gout arthritis by promoting antioxidant signaling in joint tissues.

To investigate the impact of Nrf2 activation on gout arthritis, researchers established a gout arthritis model in mice by intra-articular injection of monosodium urate (MSU) crystals. Dose-dependent inhibition of joint inflammation, mechanical, and heat hypersensitivities was observed by activating Nrf2 through the administration of the oltipraz activator 1 hour before and at 5, 23, and 47 hours after model establishment.

The researchers observed that the administration of oltipraz in varying doses (50, 100, or 150 mg/kg, intraperitoneal) both before and after model establishment led to dose-dependent inhibition of joint inflammation, as well as mechanical and heat hypersensitivities in the model mice. Oltipraz at a concentration of 100 mg/kg effectively reversed gait impairments without altering locomotor activity and reduced neutrophil infiltrations in the ankle joints.

In vitro studies further demonstrated that oltipraz inhibited MSU-induced reactive oxygen species (ROS) production in mouse macrophages and ameliorated mitochondrial bioenergetics impairments caused by MSU. In vivo ROS imaging, combined with biochemical assays, confirmed the antioxidant effects of oltipraz.

The activation of Nrf2 also proved effective in inhibiting the overproduction of pro-inflammatory cytokines in the ankle joint and attenuating the overexpression and enhancement of the transient receptor potential vanilloid 1 channel in dorsal root ganglion neurons innervating the hind limb.