Potential Nephroprotective Effect of Dorsomorphin Homolog 1 (DMH1) in a rat model of diabetic nephropathy.

Abstract

Diabetic nephropathy (DN) represents the most common cause of end-stage renal disease. On the other hand, Bone Morphogenetic Protein signaling pathway (BMP/Smad) is one of the most interesting prophylactic targets, since inhibition of this pathway may preserve kidney functions. Therefore, a BMP pharmacological inhibitor, Dorsomorphin Homolog 1 (DMH1) was used to assess the potential nephroprotective effect in an animal model of DN. STZ-induced diabetic rat was the selected model to assess the nephroprotective effect of DMH1(5 mg/kg) for eight weeks. Rats were divided into normal control (C=10), diabetic control (DC=10), diabetic+vehicle (DV=10) and diabetic DMH1-treated rats (DT=10). Fasting blood glucose (FBG) level was measured on a weekly basis. Then, glycated hemoglobin (HbA1c), serum Creatinine (sCr), Cystatin-C (Cys-C) and Blood Urea Nitrogen (BUN) were measured by the end of the experiment. Furthermore, Tumor Necrosis Factor (TNF-α), Interleukin-6 (IL-6) and Malondialdehyde (MDA) levels were determined in kidney tissues. The histopathological study was also performed using Hematoxylin and Eosin (H&E), Periodic acid Schiff (PAS) and Masson's trichrome stains. DMH1 treatment has significantly reduced HbA1c along with sCr, Cys-C and BUN vs. the diabetic non-treated groups (p< 0.001). Furthermore, TNF-α, IL-6 and MDA levels were also significantly decreased in the DT group compared to the diabetic non-treated groups (p< 0.001). This improvement was further confirmed and found in correspondence with histopathological findings. The present findings revealed a nephroprotective activity of DMH1 against STZ-induced DN in rats. DMH1 also showed anti-inflammatory and antioxidant activities, which may explain part of the nephroprotective mechanism. This can shed light on the importance of DMH1 and BMP/Smad pathway for further experimental studies.