Effects of Simvastatin on Gentamicin-induced kidney injury in rats
Subject Areas :
Veterinary Clinical Pathology
Zahra Baniasadi Rad
1
,
Akram Eidi
2
,
Pejman Mortazavi
3
,
Ali Haeri Rohani
4
1 - MSc of Physiology, Department of Biology, Science and Research Branch, Islamic Azad University, Tehran, Iran.
2 - Full Professor, Department of Biology, Science and Research Branch, Islamic Azad University, Tehran, Iran.
3 - Associate Professor, Department of Pathology, Faculty of Veterinary Medicine, Science and Research Branch, Islamic Azad University, Tehran, Iran.
4 - Full Professor, Department of Biology, Science and Research Branch, Islamic Azad University, Tehran, Iran.
Received: 2017-10-01
Accepted : 2018-12-05
Published : 2019-07-23
Keywords:
Gentamicin,
Rats,
Nephrotoxicity,
Simvastatin,
Abstract :
Consumption of gentamicin causes damage to cochlear part of ear and reversible kidney toxicity. Various compounds such as simvastatin have been suggested to reduce the side effects of gentamicin. The present study was conducted to investigate the effect of simvastatin in decreasing kidney damage due to gentamicin consumption in male Wistar rats. For this purpose, the rats were administrated simvastatin (5, 10 and 20 mg/kg daily) through gavage for 30 days. At the same time, they received gentamicin (40 mg/kg) intraperitoneally. The serumic levels of uric acid, sodium, potassium, BUN (blood urea nitrogen), creatinine, and albumin were measured and statistically analyzed using one-way analysis of variance and Tukey post hoc test. Significance was defined as p < /em>>0.05. Significant increase of creatinine (p < /em>>0.01), urea (p < /em>>0.001), BUN (p < /em>>0.001), and uric acid (p < /em>>0.001) and significant decrease of albumin (p < /em>>0.01) and sodium (p < /em>>0.01) was observed in the gentamicin-induced renal damage group in comparison to the normal control group. Treatment with simvastatin (20 mg/kg) in the animals suffering from kidney damage caused significant decrease of creatinine (p < /em>>0.01), urea (p < /em>>0.01), BUN (p < /em>>0.001) and uric acid levels (p < /em>>0.001) and significant increase in albumin (p < /em>>0.05) and sodium levels (p < /em>>0.01). The results of the present research indicate that simvastatin could improve kidney damage due to consumption of gentamicin in rats.
References:
Abotaleb, N., Pazouki, H., Homayoon, H. and Nouri, J. (1389). Simvastatin-induced renal protection against ischemia reperfusion injury mediated by activation of ATP-sensitive potassium channels. Razi Journal of Medical Sciences, 71(7): 7-13. [In Persian]
Ahlfors, C.E., Wennberg, R.P., Ostrow, J.D. and Tiribelli, C. (2009). Unbound (Free) bilirubin: improving the paradigm for evaluating neonatal jaundice. Clinical Chemistry, 55(7): 1288-1299.
Arboix, A., Garcia-Eroles, L., Oliveres, M., Targa, C., Balcells, M. and Massons, J. (2010). Pretreatment with statins improves early outcome in patients with first-ever ischaemic stroke: a pleiotropic effect of statins or a beneficial effect of hypercholesterolemia? BioMedCentral the Open Access Publisher Neurology, 10(18): 1-11.
Badyal, D.K. and Dadhich, A.P. (2001). Cytochrome P450 and drug interactions. Indian Journal of Pharmacology, 33(1): 248-259.
Bayorh, M.A., Ganafa, A.A., Eatman, D., Walton, M. and Feuerstein, G.Z. (2005). Simvastatin and losartan enhance Feuerstein GZ. Simvastatin and losartan enhance nitric oxide and reduce oxidative stress in salt induced hypertension. American Journal of Hypertension, 18(11): 1496-1502.
Bert, S., Gouyon, Y.B. and Semana, D.S. (2004). Calcium, sodium and potassium urinary excretion during the first five days of life in very preterm infants. Karger Journal Neonatology, 85(1): 37-41.
Derakhshanfar, A., Bidadkosh, A. and Kazeminia, S. (2007). Vitamin E protection against gentamicin-induced nephrotoxicity in rats: a biochemical and histopathologic study. Iranian Journal of Veterinary Research, 20(3): 231-238. [In Persian]
Esposito, E., Rinaldi, B., Mazzon, E., Donniacuo, M., Impellizzer, D., Paterniti, I., et al. (2012). Anti-inflammatory effect of simvastatin in an experiment model of spinal cord trauma: involvement of PPAR-α. Journal of Neuroinflammation, 26(9): 1-81.
Ghosh, B., Sengupta, S., Bhattacharjee, B., Majumder, A. and Sarkar, S.B. (2004). Fenofibrate-induced myopathy. Neurology India, 52(2): 268-269.
Jabbari, M., Rostami, Z., Jenabi, A., Shoolami, Z.L. and Mooraki, A. (2011). Simvastatin Ameliorates Gentamicin-Induced Renal Injury in Rats. Saudi Journal of Kidney Diseases and Transplantation, 22(6): 1181-1186.
Krycer, J.R., Phan, L. and Brown, A.J. (2012). A key regulator of cholesterol homoeostasis, SREBP-2, can be targeted in prostate cancer cells with natural products. Biochemical Journal, 446(2): 191-201.
Koh, K.K., Sakuma, I. and Quon, M.J. (2011). Differential metabolic effects of distinct statins. Atherosclerosis, 215(1): 1-8.
Lefer, D.J., Scalia, R., Jones, S.P., Sharp, B.R., Hoffmeyer, M.R., Farvid, A.R., et al. (2001). HMG-CoA reductase inhibition protects the diabetic myocardium from ischemia-reperfusion injury. FASEB (Federation of American Societies for Experimental Biology) Journal, 15(8): 1454-1456.
Lopez Novoa, J.M., Quiros, Y., Vicente, L., Morales, A.I. and Lopez-Hernandez, F.J. (2011). New insights into the mechanism of aminoglycoside nephrotoxicity: an integrative point of view. Kidney International, 79(1): 33-45.
Mooradian, A.D., Haas, M.J., Batejko, O., Hovsepyan, M. and Feman, S.S. (2005). Statins ameliorate endothelial barrier per- permeability changes in the cerebral tissue of strepto zotocin- induced diabetic rats. American Diabetes Association, 54(10): 2977-2982.
Pastori, D., Polimeni, L., Baratta, F., Pani, A., Del Ben, M. and Angelico, F. (2015). The efficacy and safety of statins for the treatment of non-alcoholic fatty liver disease. Digestive and Liver Disease, 47(1): 4-11.
Pound, E.M., Kang, J.X. and Leaf, A. (2001). Partitioning of polyunsaturated fatty acids, which prevent cardiac arrhythmias, into phospholipid cell membranes. Journal of Lipid Research, 42(3): 346-351.
Quiros, Y., Vicente-Vicente, L., Morales, A.I., López-Novoa, J.M. and López-Hernández, F.J. (2011). An integrative overview on the mechanisms underlying the renal tubular cytotoxicity of gentamicin. Toxicological Sciences, 119(2): 245-256.
Rahman, M., Shad, F. and Smith, M.C. (2012). Acute kidney injury: a guide to diagnosis and management. American Family Physician, 86(7): 631-639.
Shekelle, P., Morton, C.S., Hardy, M., Coulter, I., Udani, J., Spar, M., et al. (2003). Effect of supplemental antioxidants vitamin C, vitamin E and coenzyme Q10 for the prevention and treatment of cardiovascular disease. Evidence Report/Technology Assessment, 86(6): 1-106.
Shishehbor, M.H., Brennan, M.L., Aviles, R.J., Penn, M.S., Spreche, D.L., Hazen, S.L., et al. (2003). Statins promote potent systemic antioxidant effects through specific inflammatory pathways. Circulation, 108(4): 426-431.
Tesfamariam, B., Frohlich, B.H. and Gregg, R.E. (1999). Differential effects of pravastatin, simvastatinand atorvastatin on Ca2+ release and vascular reactivity. Journal of Cardiovascular Pharmacology, 34(1): 95-101.
Vaquero, M., Caballero, R., Gómez, R., Núñez, L., Tamargo, J. and Delpón, E. (2007). Effects of atorvastatin and simvastatin on atrial plateau currents. Journal of Molecular and Cellular Cardiology, 42(5): 931-945.
Vaughan, C.J., Gotto, A.M. and Basson, C.T. (2000). The evolving role of statins in the management of atherosclerosis. Journal of the American College of Cardiology, 35(1): 1-10.
Von Stechow, D., Fish, S., Yahalom, D., Bab, I., Chorev, M., Muller, R., et al. (2003). Does simvastatin stimulate boneformation in vivo. Digital Access to Scholarship at Harvard, 4(8): 1-8.
Yagi, S., Akaike, M., Aihara, K., Iwase, T., Ishikawa, K., Yoshida, S., et al. (2011). Effect of low-dose (1 mg/day) pitavastatin on left ventricular diastolic function and albuminuria in patients with hyperlipidemia. AM (Ante Meridian) Journal of Cardiology, 107(11): 1644-1649.
_||_
Abotaleb, N., Pazouki, H., Homayoon, H. and Nouri, J. (1389). Simvastatin-induced renal protection against ischemia reperfusion injury mediated by activation of ATP-sensitive potassium channels. Razi Journal of Medical Sciences, 71(7): 7-13. [In Persian]
Ahlfors, C.E., Wennberg, R.P., Ostrow, J.D. and Tiribelli, C. (2009). Unbound (Free) bilirubin: improving the paradigm for evaluating neonatal jaundice. Clinical Chemistry, 55(7): 1288-1299.
Arboix, A., Garcia-Eroles, L., Oliveres, M., Targa, C., Balcells, M. and Massons, J. (2010). Pretreatment with statins improves early outcome in patients with first-ever ischaemic stroke: a pleiotropic effect of statins or a beneficial effect of hypercholesterolemia? BioMedCentral the Open Access Publisher Neurology, 10(18): 1-11.
Badyal, D.K. and Dadhich, A.P. (2001). Cytochrome P450 and drug interactions. Indian Journal of Pharmacology, 33(1): 248-259.
Bayorh, M.A., Ganafa, A.A., Eatman, D., Walton, M. and Feuerstein, G.Z. (2005). Simvastatin and losartan enhance Feuerstein GZ. Simvastatin and losartan enhance nitric oxide and reduce oxidative stress in salt induced hypertension. American Journal of Hypertension, 18(11): 1496-1502.
Bert, S., Gouyon, Y.B. and Semana, D.S. (2004). Calcium, sodium and potassium urinary excretion during the first five days of life in very preterm infants. Karger Journal Neonatology, 85(1): 37-41.
Derakhshanfar, A., Bidadkosh, A. and Kazeminia, S. (2007). Vitamin E protection against gentamicin-induced nephrotoxicity in rats: a biochemical and histopathologic study. Iranian Journal of Veterinary Research, 20(3): 231-238. [In Persian]
Esposito, E., Rinaldi, B., Mazzon, E., Donniacuo, M., Impellizzer, D., Paterniti, I., et al. (2012). Anti-inflammatory effect of simvastatin in an experiment model of spinal cord trauma: involvement of PPAR-α. Journal of Neuroinflammation, 26(9): 1-81.
Ghosh, B., Sengupta, S., Bhattacharjee, B., Majumder, A. and Sarkar, S.B. (2004). Fenofibrate-induced myopathy. Neurology India, 52(2): 268-269.
Jabbari, M., Rostami, Z., Jenabi, A., Shoolami, Z.L. and Mooraki, A. (2011). Simvastatin Ameliorates Gentamicin-Induced Renal Injury in Rats. Saudi Journal of Kidney Diseases and Transplantation, 22(6): 1181-1186.
Krycer, J.R., Phan, L. and Brown, A.J. (2012). A key regulator of cholesterol homoeostasis, SREBP-2, can be targeted in prostate cancer cells with natural products. Biochemical Journal, 446(2): 191-201.
Koh, K.K., Sakuma, I. and Quon, M.J. (2011). Differential metabolic effects of distinct statins. Atherosclerosis, 215(1): 1-8.
Lefer, D.J., Scalia, R., Jones, S.P., Sharp, B.R., Hoffmeyer, M.R., Farvid, A.R., et al. (2001). HMG-CoA reductase inhibition protects the diabetic myocardium from ischemia-reperfusion injury. FASEB (Federation of American Societies for Experimental Biology) Journal, 15(8): 1454-1456.
Lopez Novoa, J.M., Quiros, Y., Vicente, L., Morales, A.I. and Lopez-Hernandez, F.J. (2011). New insights into the mechanism of aminoglycoside nephrotoxicity: an integrative point of view. Kidney International, 79(1): 33-45.
Mooradian, A.D., Haas, M.J., Batejko, O., Hovsepyan, M. and Feman, S.S. (2005). Statins ameliorate endothelial barrier per- permeability changes in the cerebral tissue of strepto zotocin- induced diabetic rats. American Diabetes Association, 54(10): 2977-2982.
Pastori, D., Polimeni, L., Baratta, F., Pani, A., Del Ben, M. and Angelico, F. (2015). The efficacy and safety of statins for the treatment of non-alcoholic fatty liver disease. Digestive and Liver Disease, 47(1): 4-11.
Pound, E.M., Kang, J.X. and Leaf, A. (2001). Partitioning of polyunsaturated fatty acids, which prevent cardiac arrhythmias, into phospholipid cell membranes. Journal of Lipid Research, 42(3): 346-351.
Quiros, Y., Vicente-Vicente, L., Morales, A.I., López-Novoa, J.M. and López-Hernández, F.J. (2011). An integrative overview on the mechanisms underlying the renal tubular cytotoxicity of gentamicin. Toxicological Sciences, 119(2): 245-256.
Rahman, M., Shad, F. and Smith, M.C. (2012). Acute kidney injury: a guide to diagnosis and management. American Family Physician, 86(7): 631-639.
Shekelle, P., Morton, C.S., Hardy, M., Coulter, I., Udani, J., Spar, M., et al. (2003). Effect of supplemental antioxidants vitamin C, vitamin E and coenzyme Q10 for the prevention and treatment of cardiovascular disease. Evidence Report/Technology Assessment, 86(6): 1-106.
Shishehbor, M.H., Brennan, M.L., Aviles, R.J., Penn, M.S., Spreche, D.L., Hazen, S.L., et al. (2003). Statins promote potent systemic antioxidant effects through specific inflammatory pathways. Circulation, 108(4): 426-431.
Tesfamariam, B., Frohlich, B.H. and Gregg, R.E. (1999). Differential effects of pravastatin, simvastatinand atorvastatin on Ca2+ release and vascular reactivity. Journal of Cardiovascular Pharmacology, 34(1): 95-101.
Vaquero, M., Caballero, R., Gómez, R., Núñez, L., Tamargo, J. and Delpón, E. (2007). Effects of atorvastatin and simvastatin on atrial plateau currents. Journal of Molecular and Cellular Cardiology, 42(5): 931-945.
Vaughan, C.J., Gotto, A.M. and Basson, C.T. (2000). The evolving role of statins in the management of atherosclerosis. Journal of the American College of Cardiology, 35(1): 1-10.
Von Stechow, D., Fish, S., Yahalom, D., Bab, I., Chorev, M., Muller, R., et al. (2003). Does simvastatin stimulate boneformation in vivo. Digital Access to Scholarship at Harvard, 4(8): 1-8.
Yagi, S., Akaike, M., Aihara, K., Iwase, T., Ishikawa, K., Yoshida, S., et al. (2011). Effect of low-dose (1 mg/day) pitavastatin on left ventricular diastolic function and albuminuria in patients with hyperlipidemia. AM (Ante Meridian) Journal of Cardiology, 107(11): 1644-1649.
