Modulation of inflammation and oxidative stress by a new thiazolidine compound (GQ-11) in a rat model of visceral ischemia

Ischemia/Reperfusion Syndrome (IRS) is a recurrent issue of vascular surgery procedures, triggered by the inflammatory response and promoting endothelial dysfunction, cytotoxicity, vasoconstriction, hypoxia and apoptosis. Given their anti-oxidant and anti-inflammatory properties, thiazolidine compounds, widely recognized as Ppar-γ agonists, are suitable candidates for IRS damage prevention. The effects of the new thiazolidine compound GQ-11 on inflammation and oxidative stress in a rat model of IRS were investigated. Male Wistar rats, fed a standard diet, were treated for 7 days with vehicle, pioglitazone (10 mg/kg) or GQ-11 (10 mg/kg) by gavage. After treatments, animals were anesthetized and underwent abdominal surgery. Livers and kidneys were collected and analyzed by qPCR for gene expression and TBARS assay for lipid peroxidation. GQ-11 induced an increase in the expression of Ppar-γ and Ppar-α in kidney and liver. The expression of pro-inflammatory cytokines such as Il-1β and Ccl-2 was decreased by GQ-11, whereas increased Vegf expression denoted a pro-angiogenic effect. Moreover GQ-11 modulated the expression of the antioxidant enzymes Catalase and Sod2 and prevented the formation of lipoperoxides. GQ-11 administration prior to vascular surgery decreased IRS-associated inflammation and oxidative stress by Ppar-γ and Ppar-α agonism, thus confirming GQ-11 as a suitable candidate for IRS damage prevention.