Preventive effects of metformin on renal ischemia-reperfusion injury in the rat
Subject Areas :
Veterinary Clinical Pathology
ahmad asghari
1
,
ghazal kashfiyeganeh
2
,
pejman mortazavi
3
1 - دانشگاه آزاد اسلامی، واحد علوم و تحقیقات، استادیار گروه علوم درمانگاهی دامپزشکی، تهران، ایران.
2 - دانشگاه آزاد اسلامی، واحد علوم و تحقیقات، دانشجوی دکترای حرفهای دامپزشکی، تهران، ایران.
3 - دانشگاه آزاد اسلامی، واحد علوم و تحقیقات، استادیار گروه پاتوبیولوژی دامپزشکی، تهران، ایران.
Received: 2014-03-07
Accepted : 2014-06-24
Published : 2014-02-20
Keywords:
Rat,
kidney,
Ischemia-reperfusion,
Metformin,
Abstract :
Renal ischemia causes oxidative stress which leads to severe and prolonged inflammatory responses following reperfusion. Re-perfusion injury in the kidney is a causal factor of acute renal failure which has been studied in different animals and clinical models. Metformin is an oral medication used alone or with other medications to treat type 2 diabetes. The purpose of this study was to evaluate the effect of metformin following the induction of ischemia-reperfusion in the rat kidney. In this study, 30 adult male Wistar rats weighing 200-250g were used which were divided randomly into three groups of 10 which include the sham group; this group had not received any medication and after only a week, the abdominal cavity was opened then left renal nephrectomy was performed and the abdominal cavity reclosed. The control group (IR): this group had not received any medication until induction of ischemia-reperfusion and after a week the abdominal cavity was opened and following ischemia- reperfusion, left kidney nephrectomy was performed. I/R+MET group: this group was gavaged with a dose of metformin (100 mg/kg) each day for a week at a same time and after a week the abdominal cavity was opened and then ischemia-reperfusion was induced and left kidney nephrectomy performed. In all groups except sham, both the renal pedicles were closed and released after 45 minutes for induction of ischemia-reperfusion. After 4 and 8 hours, left kidney nephrectomy was performed. At day zero (before drug administration) and after the end of ischemia-reperfusion and during renal nephrectomy, blood samples were collected and serum creatinine and BUN levels were examined. The data obtained analyzed by ANOVA on significant levels (p<0.05). Histopathological results of I/R+MET group showed degeneration and cell swelling in some tubules at low levels and mild pyknosis and the nucleus and cytoplasm of most tubules were normal. The serological results obtained indicated a slight and insignificant decrease in BUN and serum creatinine in I/R+MET group compared with the I/R group. This study showed that metformin relatively protects the kidney from ischemia-reperfusion injury.
References:
Ansari, M. (2011). Renoprotective effects of combining ACE inhibitors and statins in experimental diabetic rats. DARU Journal of Pharmaceutical Sciences, 19(5): 322-325.
Behradmanesh, S. and Nasri, H. (2013). Association of serum calcium with level of blood pressure in type 2 diabetic patients. Journal of Nephropathology, 2(4): 254.
Bonnefont-Rousselot, D. and Raji, B. (2003). An intracellular modulation of free radical production could contribute to the beneficial effects of metformin towards oxidative stress. Metabolism, 52(5): 586-589.
Cheng, J. and Truong, L.D. (2010). Serum-and glucocorticoid-regulated kinase 1 is upregulated following unilateral ureteral obstruction causing epithelial–mesenchymal transition. Kidney International, 78(7): 668-678.
Cicero, A., Tartagni, E. and Ertek, S. (2012). Metformin and its clinical use: new insights for an old drug in clinical practic, Archive Medical Science, 8: 907-917.
Detaille, D., Guigas, B., Chauvin, C., Batandier, C., Fontaine, E., Wiernsperger, N., et al. (2005). Metformin prevents high-glucose–induced endothelial cell death through a mitochondrial permeability transition-dependent process. Diabetes, 54(7): 2179-2187.
Hansson, G.K. (2005). Inflammation, atherosclerosis, and coronary artery disease. New England Journal of Medicine, 352(16): 1685-1695.
Hou, X., Song, J., Li, X.N., Zhang, L., Wang, X., Chen, L., et al. (2010). Metformin reduces intracellular reactive oxygen species levels by upregulating expression of the antioxidant thioredoxin via the AMPK-FOXO3 pathway. Biochemical and biophysical research communications, 396(2): 199-205.
Morales, A.I., Detaille, D., Prieto, M., Puente, A., Briones, E., Arévalo, M., et al. (2010). Metformin prevents experimental gentamicin-induced nephropathy by a mitochondria-dependent pathway. Kidney International, 77(10): 861-869.
Nye, H.J. and Herrington, W.G. (2011). Metformin: the safest hypoglycaemic agent in chronic kidney disease? Nephron Clinical Practice, 118(4): c380-c383.
Rafieian-Kopaei, M., Baradaran, A., Merrikhi, A., Nematbakhsh, M., Madihi, Y. and Nasri H. (2013). Efficacy of co-administration of garlic extract and metformin for prevention of gentamicin–renal toxicity in wistar rats: A biochemical study. International Journal of Preventive Medicine, 4(3): 258.
Soraya, H., Farajnia, S., Khani, S., Rameshrad, M., Khorrami, A., Banani, A., et al. (2012). Short-term treatment with metformin suppresses toll like receptors (TLRs) activity in isoproterenol-induced myocardial infarction in rat: Are AMPK and TLRs connected? International Immunopharmacology, 14(4): 785-791.
Taheri, N., Azarmi,Y., Neshat, M., Garjani, A. and Doustar, Y. (2012). Study the effects of metformin on renal function and structure after unilateral ischemia-reperfusion in rat. Research in Pharmaceutical Sciences, 7(5): S77.
Tankova, T. (2002). Current indications for metformin therapy. Romanian journal of internal medicine. Revue Roumaine de Medecine Interne, 41(3): 215-225.
Vesey, D.A., Cheung, C., Pat, B., Endre, Z., Gobé, G. and Johnson, D.W. (2004). Erythropoietin protects against ischaemic acute renal injury. Nephrology Dialysis Transplantation, 19(2): 348-355.