Diacerein alleviates kidney injury through attenuating inflammation and oxidative stress in obese insulin-resistant rats

A link between inflammation with obesity and metabolic syndrome has been found in patients with chronic kidney disease (CKD). Diacerein is an anthraquinone used to treat osteoarthritis that exerts anti-inflammatory action by inhibiting the synthesis and activity of proinflammatory cytokines. This study aimed to investigate the protective effect of diacerein on renal function and renal organic anion transporter 3 (Oat3) function in obese insulin-resistant condition. Obese insulin-resistant rats were induced by feeding a high-fat diet in male Wistar rats for 16 weeks. Diacerein or metformin (positive control) (30 mg/kg/day) was administered orally for 4 weeks after insulin resistance had been confirmed. Obese insulin-resistant rats showed an impaired renal function as indicated by the increased serum creatinine and microalbuminuria along with the decreased renal Oat3 function and expression. Importantly, diacerein treatment not only improved insulin resistance but also restored renal function. The decreased renal malondialdehyde level, expressions of PKC alpha, angiotensin 1 receptor (AT1R), Nrf2, and HO-1, and increased expression of SOD2 were observed in diacerein treatment group, indicating the attenuation of renal oxidative stress condition. Moreover, renal inflammation and renal damage were also alleviated in diacerein-treated rats. Our results demonstrated for the first time that diacerein was effective to improve renal function and renal Oat3 function in obese insulin-resistance condition mediated by suppressing renal oxidative stress and inflammation. These findings suggest that anti-inflammatory agents can be used therapeutically to improve metabolic disorder and prevent organ dysfunctions in pre-diabetic condition.