Several studies verified that NOXs which is comprise isoform NOX1 to 5, Duox 1 and 2, trigger diabetic nephropathy incidences in diabetes. Recently, it has been studied that the expression of NOX5 is increased in the patients with diabetic nephropathy over other isoforms and the importance of NOX5 in the development of therapeutic agents has been suggested. Previous study investigated that APX-115 has the effect of pan-NOX inhibition in type 2 diabetic mice.

However, since the NOX5 gene is absent in the mouse, we evaluated the pan-NOX inhibitory of APX-115 in Nox5 transgenic mouse. Wild type and renal podocyte specifically NOX5 transgenic mice (NOX5 pod+) were fed high fat diet (60% kcal fat) and treated APX-115 (60mg/kg) by oral gavage for 14 weeks.

APX-115 significantly improved pancreatic beta cell function with decreased fasting blood glucose and increased insulin levels. And serum total cholesterol, triglycerides and urinary albumin/creatinine levels were also significantly decreased by APX-115 treatment. In NOX5 pod+ mice kidney, increased NOX5 mRNA expression, increased desmin and reduced podocin protein expressions were also significantly recovered by APX-115. Moreover, APX-115 inhibited inflammatory related protein expressions such as TRAF6.

Therefore, these data suggest that APX-115 might be a promising therapy for diabetic nephropathy by an efficacy as a pan-NOX inhibitor including NOX5 inhibition and anti-inflammatory effects.


E. Lee: None. C.H. Chung: None. J. Huh: None. S. Lee: None.

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