Activation of AQP4, p66Shc and endoplasmic reticulum stress is involved in inflammation by carrageenan and is suppressed by argirein, a derivative of rhein

Abstract

We investigated the effect of argirein on acute inflammation edema and examined that aquaporin 4 (AQP4), p66Shc and activating transcription factor (ATF-6) might be involved in carrageenan-induced rat paw inflammation and be reversed by argirein, rhein and indometacin, but not L-arginine. Inflammation was produced by carrageenan injected into rat paw and treated orally with argirein (100 mg/kg), rhein (100 mg/kg), L-arginine (100 mg/kg) or indometacin (5 mg/kg). Inflammatory oedema and biomarkers were examined. Swelling was reduced by argirein, rhein and indometacin; argirein was more effective than rhein at 1 h following medication. Activation of AQP4, p66Shc, ATF-6, NADPH oxidase subunits p22phox, gp91phox and matrix metalloproteinase 2 (P < 0.01) was significant and was suppressed by arginine, rhein and indometacin but not by l-arginine. Activated AQP4, endoplasmic reticulum stress and p66Shc were actively implicated in the inflammation and these were suppressed by argirein, and its activity is favorable due to synergism in combination with L-arginine.