Amin Hasanvand
1,2,3,4, Hossein Amini-Khoei
5, Samane Jahanabadi
6, Mohammad-Reza Hadian
7, Alireza Abdollahi
8, Seyed Mohammad Tavangar
9, Shahram jtemaei Mehr
1,2,3*, Ahmad Reza Dehpour
1,2,3*1 Department of Pharmacology, School of Medicine, International Campus, Tehran University of Medical Sciences (IC-TUMS), Tehran, Iran
2 Department of Pharmacology, School of Medicine, Tehran University of Medical Sciences, Tehran, Iran
3 Experimental Medicine Research Center, Tehran University of Medical Sciences, Tehran, Iran.
4 Nutritional Health Research Center, Department of Pharmacology and Toxicology, Faculty of Pharmacy, Lorestan University of Medical Sciences, Khorramabad, Iran
5 Medical Plants Research Center, Basic Health Sciences Institute, Shahrekord University of Medical Sciences, Shahrekord, Iran
6 Faculty of Pharmacy, Shahid Sadoughi University of Medical Sciences, Yazd, Iran
7 Department of Physical Therapy, Rehabilitation Faculty, Tehran University of Medical Sciences, Tehran, Iran
8 Department of Pathology, Imam Khomini Complex Hospital, Tehran University of Medical Sciences, Tehran, Iran
9 Department of Pathology, Shariati Hospital, Tehran University of Medical Sciences, Tehran, Iran
Abstract
Background: Nephropathy is the main problem of diabetes and can be classified into several phases according to the presence of albuminuria. Adenosine monophosphate-activated protein kinase (AMPK) operates as a sensor of energy charge.
Objectives: The aim of our study was to evaluate the reno-protective properties of AMPK signaling pathway against streptozotocin (STZ)-induced nephropathy in the rat.
Materials and Methods: Forty male Wistar rats were randomly distributed into four groups. Group 1 was normal rats (N group); group 2 was diabetic rats (D group); group 3 received diabetic rats + metformin (DM group), and group 4 received giabetic rats + metformin + dorsomorphin (DMD group). Serum albumin, uric acid, total protein and creatinine for estimation of renal injury were measured. Finally, the histological study was evaluated.
Results: Reduction of body weight, albumin and total protein in the diabetic rat was reversed by metformin administration. Our results showed that serum uric acid and creatinine were significantly increased in diabetic rats and decreased after treatment with metformin in diabetic rats. AMPK improved the histopathology and morphological changes in STZinduced diabetic rats. Administration of dorsomorphin (AMPK inhibitor) with metformin can reverse the beneficial effects of AMPK.
Conclusions: AMPK signaling pathway ameliorates diabetic nephropathy by modifications of serum albumin, uric acid, total protein, creatinine and attenuation of kidney damage.
Implication for health policy/practice/research/medical education:
In this experimental study, we found that activation of AMPK via metformin can protect nephropathy against STZ-induced diabetes in models of rats. The main mechanism of AMPK in renoprotective effects was increased serum albumin and total protein levels and decreased serum uric acid and creatinine levels after treatment with metformin in diabetic rats.
Please cite this paper as: Hasanvand A, Amini-Khoei H, Jahanabadi S, Hadian MR, Abdollahi A, Tavangar SM, et al. Metformin attenuates streptozotocin-induced diabetic nephropathy in rats through activation of AMPK signaling pathway. J Nephropathol. 2018;7(1):37-42. DOI: 10.15171/jnp.2018.11.