بررسی اثر سیمواستاتین بر آسیب کلیوی القاء‌شده توسط جنتامایسین در موش صحرایی
محورهای موضوعی :
آسیب شناسی درمانگاهی دامپزشکی
زهرا بنی اسدی راد
1
,
اکرم عیدی
2
,
سید پژمان مرتضوی
3
,
علی حائری
4
1 - کارشناسی ارشد فیزیولوژی، گروه زیست‌شناسی، دانشکده علوم پایه، واحد علوم و تحقیقات، دانشگاه آزاد اسلامی، تهران، ایران.
2 - استاد فیزیولوژی، گروه زیست‌شناسی، دانشکده علوم پایه، واحد علوم و تحقیقات، دانشگاه آزاد اسلامی، تهران، ایران.
3 - دانشیار پاتولوژی، گروه پاتولوژی، دانشکده دامپزشکی، واحد علوم و تحقیقات، دانشگاه آزاد اسلامی، تهران، ایران.
4 - استاد فیزیولوژی، گروه زیست‌شناسی، دانشکده علوم پایه، واحد علوم و تحقیقات، دانشگاه آزاد اسلامی، تهران، ایران.
تاریخ دریافت : 1396/07/09
تاریخ پذیرش : 1397/09/14
تاریخ انتشار : 1398/05/01
کلید واژه:
موش صحرایی,
جنتامایسین,
سیمواستاتین,
سمیت کلیوی,
چکیده مقاله :
مصرف جنتامایسین موجب آسیب به بخش حلزونی گوش و مسمومیت برگشت پذیر کلیه می شود. ترکیبات مختلفی از جمله سیمواستاتین برای کاهش عوارض جانبی جنتامایسین پیشنهاد شده است. در مطالعه حاضر بررسی اثر سیمواستاتین درجهت کاهش آسیب کلیوی ناشی از مصرف آنتی بیوتیک جنتامایسین در موش های صحرایی نر نژاد ویستار انجام گرفت.بدین منظور موش‌های صحرایی به مدت 30 روز به صورت گاواژ با دوز های 5، 10 و 20 میلی گرم بر کیلو گرم وزنبدن سیمواستاتین، به‌طور روزانه تیمار شده و هم زمان جنتامایسین را با غلظت 40 میلی گرم بر کیلو گرم وزنبدن به صورت تزریق درون صفاقی دریافت کردند. سطوح اسید اوریک، اوره، سدیم، پتاسیم، نیتروژن اوره خون (blood urea nitrogen; BUN)، کراتینین و آلبومین در سرم موش هااندازه گیری گردیده و با استفاده از آزمون تحلیل واریانس یک طرفه و آزمون تعقیبی توکی مورد واکاوی آماری قرار گرفت. مقادیر 05/0>p معنی دار در نظر گرفته شد. افزایش معنی دار میزان کراتینین (01/0p <)، اوره (001/0p <)، نیتروژن اوره خون (001/0p <) و اسید اوریک (001/0p <) و کاهش معنی دار آلبومین (01/0p <) و سدیم (01/0p <) در حیوانات گروه دچار آسیب کلیوی توسط جنتامایسین در مقایسه با گروه کنترل سالم، مشاهده شد. تیمار با سیمواستاتین در غلظت 20 میلی گرم بر کیلو گرم وزن بدن در حیوانات دچار آسیب کلیوی باعث کاهش معنی دار کراتینین (01/0p <)، اوره (01/0p <)، نیتروژن اوره خون (001/0p <) و اسید اوریک (001/0p <) و افزایش معنی دار آلبومین (05/0p <) و سدیم (01/0p <) شد. نتایج مطالعه حاضر نشان دهنده بهبود آسیب کلیه ها در پی مصرف جنتامایسین در موش های صحرایی توسط سیمواستاتینمی باشد.
چکیده انگلیسی:
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.
منابع و مأخذ:
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.
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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.
