The protective effect of telmisartan in Type 2 diabetes rat kidneys is related to the downregulation of thioredoxin-interacting protein

Abstract

Thioredoxin-interacting protein (Txnip), an inhibitor of thioredoxin (Trx), increases in diabetic nephropathy and promotes oxidative stress. The angiotensin II (Ang II) receptor blocker telmisartan may protect renal function in diabetic models and patients via multiple effects including antioxidation. However, its mechanism has not been fully elucidated, and its relationship to Txnip remains unclear. This study aimed to investigate whether telmisartan ameliorates oxidative stress by regulating Txnip and Trx expression in Type 2 diabetic rat kidneys and explore the possible relationship between renoprotection by telmisartan and Txnip. Twenty-one rats were equally divided into control (C), streptozotocin-induced diabetic (D), and telmisartan- treated diabetic (T) groups. Txnip and Trx expression in rat kidneys was analyzed by immunohistochemistry, RTPCR, and western blot. Peroxisome proliferator-activated receptor- γ (PPARγ), NADPH oxidase activity, and parameters of renal function and oxidative stress were also measured. Trx and PPARγ were significantly decreased, and Txnip expression and NADPH oxidase activity markedly increased, in the D and T groups compared to the C group. After telmisartan treatment, Trx and PPARγ were upregulated, while Txnip expression and NADPH oxidase activity were downregulated. Parameters of renal function and oxidative stress were improved by telmisartan. Telmisartan ameliorates oxidative stress and protects renal function in Type 2 diabetic rat kidneys. The downregulation of Txnip by telmisartan may be associated with PPARγ activation.