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

A. Esmat, A.M. Alzahrani, B.T. Alharthy, W.S. Ramadan, M.A.A. Sattar Ahmad

Department of Pharmacology, Faculty of Medicine, King Abdulaziz University, Jeddah, Kingdom of Saudi Arabia. aalzahrani3093@stu.kau.edu.sa

---

• Pharmacology

OBJECTIVE: 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.

MATERIALS AND METHODS: 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.

RESULTS: 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.

CONCLUSIONS: 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.

Free PDF Download