Inhibition of 12‐lipoxygenase reduces renal inflammation and damage in steptozotocin‐induced diabetic mice

Abstract

Studies have shown that the 12/15-lipoxygenase (12/15-LO) pathway is activated in diabetes. We hypothesize that 12-LO inhibition attenuates renal injury in streptozotocin-induced type 1 diabetes. Diabetes was induced by streptozotocin in C57 black mice and verified by urine glucose (¡Ý300 mg/dl) after three months. Mice were divided into 4 groups: control, diabetic, diabetic treated with the selective 12-LO inhibitor baicalein for the last month of diabetes and diabetic treated with baicalein for all three months. Induction of diabetes significantly increased proteinuria (4.9±1.1 vs. 1.1±0.1 mg/day) and inhibition of 12-LO with baicalein lowered proteinuria in both the one and three month-treated groups (1.7±0.2 & 1.9± 0.1 mg/day, respectively). Urinary TBARs excretion, a marker of oxidative stress, was significantly elevated in diabetic mice (8.3±1 vs. 0.04±0.004 μmol/day) and inhibition of 12-LO also reduced this elevation in both baicalein-treated groups. Induction of diabetes increased urinary MCP-1 excretion and renal COX-2 expression and these changes were attenuated with baicalein treatment. These results suggest that increased 12-LO in diabetes could activate COX-2, oxidative stress, and inflammatory pathways and 12-LO inhibition not only prevents but potentially decreases the progression of diabetic renal injury.