Melatonin and/or rowatinex attenuate streptozotocin-induced diabetic renal injury in rats
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摘要
The study aimed to explore the prophylactic effect of melatonin, rowatinex; a naturally occurring renal drug, and its combination on diabetic nephropathy in type 2 diabetic rats. Diabetes was induced by intraperitoneal injection of a single dose of streptozotocin(50 mg/g body weight). Three days before diabetes induction, rats were daily treated with melatonin, rowatinex and their combination continuously for 8 weeks. Evaluation was done through measuring blood urea nitrogen(BUN), serum uric acid, serum creatinine, urine creatinine, creatinine clearance, nitric oxide(NO), malondialdehyde(MDA), superoxide dismutase(SOD), glutathione(GSH), total antioxidant capacity(TAC),kidney injury molecule-1(KIM-1), heat shock protein-70(HSP-70), caspase-3, transforming growth factor β1(TGFβ1), DNA degradation by the comet assay and total protein contents. Histopathologic study was also done for the kidney and the pancreas. Drastic changes in all measured parameters of the diabetic rats were observed. Treatment with melatonin and rowatinex showed amelioration to variable degrees. In conclusion, melatonin showed the most potent effect on protecting rats from deleterious action of diabetic nephropathy followed by its combination with rowatinex.
The study aimed to explore the prophylactic effect of melatonin, rowatinex; a naturally occurring renal drug, and its combination on diabetic nephropathy in type 2 diabetic rats. Diabetes was induced by intraperitoneal injection of a single dose of streptozotocin(50 mg/g body weight). Three days before diabetes induction, rats were daily treated with melatonin, rowatinex and their combination continuously for 8 weeks. Evaluation was done through measuring blood urea nitrogen(BUN), serum uric acid, serum creatinine, urine creatinine, creatinine clearance, nitric oxide(NO), malondialdehyde(MDA), superoxide dismutase(SOD), glutathione(GSH), total antioxidant capacity(TAC),kidney injury molecule-1(KIM-1), heat shock protein-70(HSP-70), caspase-3, transforming growth factor β1(TGFβ1), DNA degradation by the comet assay and total protein contents. Histopathologic study was also done for the kidney and the pancreas. Drastic changes in all measured parameters of the diabetic rats were observed. Treatment with melatonin and rowatinex showed amelioration to variable degrees. In conclusion, melatonin showed the most potent effect on protecting rats from deleterious action of diabetic nephropathy followed by its combination with rowatinex.
The study aimed to explore the prophylactic effect of melatonin, rowatinex; a naturally occurring renal drug, and its combination on diabetic nephropathy in type 2 diabetic rats. Diabetes was induced by intraperitoneal injection of a single dose of streptozotocin(50 mg/g body weight). Three days before diabetes induction, rats were daily treated with melatonin, rowatinex and their combination continuously for 8 weeks. Evaluation was done through measuring blood urea nitrogen(BUN), serum uric acid, serum creatinine, urine creatinine, creatinine clearance, nitric oxide(NO), malondialdehyde(MDA), superoxide dismutase(SOD), glutathione(GSH), total antioxidant capacity(TAC),kidney injury molecule-1(KIM-1), heat shock protein-70(HSP-70), caspase-3, transforming growth factor β1(TGFβ1), DNA degradation by the comet assay and total protein contents. Histopathologic study was also done for the kidney and the pancreas. Drastic changes in all measured parameters of the diabetic rats were observed. Treatment with melatonin and rowatinex showed amelioration to variable degrees. In conclusion, melatonin showed the most potent effect on protecting rats from deleterious action of diabetic nephropathy followed by its combination with rowatinex.
引文
[1] Soro-Paavonen A, Forbes JM. Novel therapeutics for diabetic micro-and macrovascular complications[J]. Curr Med Chem,2006, 13(15):1777-1788.
[2] Moe OW, Berry CA, Rector FCJr. Renal Transport of Glucose,Amino Acids, Sodium, Chloride, and Water in the Kidney[M].Edited by Brenner BM. Philadelphia, USA:W.B. Saunders;2000; 375-415.
[3] Sternberg M, Cohen-Forterre L, Peyroux J. Connective tissue in diabetes mellitus:biochemical alterations of the intercellular matrix with special reference to proteoglycans, collagens and basement membranes[J]. Diabete Metab, 1985, 11(1):27-50.
[4] Bolton WK, Sturgill BC. Spontaneous glomerular sclerosis in aging Sprague-Dawley rats. II. Ultrastructural studies[J]. Am J Pathol, 1980, 98(2):339-356.
[5] Zafar M, Naqvi SNU. Effects of STZ-Induced diabetes on the relative weights of kidney, liver and pancreas in albino rats:a comparative study[J]. Int JMorphol, 2010, 28(1):135-142.
[6] Fadillioglu E, Kurcer Z, Parlakpinar H, et al. Melatonin treatment against remote organ injury induced by renal ischemia reperfusion injury in diabetes mellitus[J]. Arch Pharm Res, 2008, 31(6):705-712.
[7] Magee PN, Swann PF. Nitroso compounds[J]. Br Med Bull,1969, 25(3):240-244.
[8] Winiarska K, Fraczyk T, Malinska D, et al. Melatonin attenuates diabetes-induced oxidative stress in rabbits[J]. J Pineal Res,2006, 40(2):168-176.
[9] Sudnikovich EJ, Maksimchik YZ, Zabrodskaya SV, et al.Melatonin attenuates metabolic disorders due to streptozotocininduced diabetes in rats[J]. Eur J Pharmacol, 2007, 569(3):180-187.
[10] Robeva R, Kirilov G, Tomova A, et al. Melatonin-insulin interactions in patients with metabolic syndrome[J]. J Pineal Res, 2008, 44(1):52-56.
[11] Cam M, Yavuz O, Guven A, et al. Protective effects of chronic melatonin treatment against renal injury in streptozotocininduced diabetic rats[J]. J Pineal Res, 2003, 35(3):212-220.
[12] Thorsten B. Preclinical and clinical overview of terpenes in thetreatment of urolithiasis[J]. Eur Urol, 2010, 9:801-826.
[13] Punithavathi VR, Anuthama R, Prince PS. Combined treatment with naringin and vitamin C ameliorates streptozotocin-induced diabetes in male Wistar rats[J]. J Appl Toxicol, 2008, 28(6):806-813.
[14] Bhandari U, Kanojia R, Pillai KK. Effect of ethanolic extract of Zingiber officinale on dyslipidaemia in diabetic rats[J]. J Ethnopharmacol, 2005, 97(2):227-230.
[15] Yavuz O, Cam M, Bukan N, et al. Protective effect of melatonin onβ-cell damage in streptozotocin-induced diabetes in rats[J].Acta Histochem, 2003, 105(3):261-266.
[16] Romics I, Siller G, Kohnen R, et al. A special terpene combination(Rowatinex(?))improves stone clearance after extracorporeal shockwave lithotripsy in urolithiasis patients:results of a placebo-controlled randomised controlled trial[J].UrolInt, 2011, 86(1):102-109.
[17] Buege JA, Aust SD. Microsomal lipid peroxidation[J]. Methods Enzymol, 1978, 52:302-310.
[18] Moron MS, Depierre JW, Mannervik B. Levels of glutathione,glutathione reductase and glutathione S-transferase activities in rat lung and liver[J]. Biochim Biophys Acta, 1979, 582(1):67-78.
[19] Nishikimi M, Appaji N, Yagi K. The occurrence of superoxide anion in the reaction of reduced phenazine methosulfate and molecular oxygen[J]. Biochem Biophys Res Commun, 1972,46(2):849-854.
[20] Moshage H, Kok B, Huizenga JR, et al. Nitrite and nitrate determinations in plasma:a critical evaluation[J]. Clin Chem,1995,41(6 Pt 1):892-896.
[21] Bradford MM. A rapid and sensitive method for the quantitation of microgram quantities of protein utilizing the principle of protein-dye binding[J]. Anal Biochem, 1976, 72:248-254.
[22] Suzuki H, Suzuki K. Rat hypoplastic kidney(hpk/hpk)induces renal anemia, hyperparathyroidism, and osteodystrophy at the end stage of renal failure[J].J Vet Med Sci,1998,60(10):1051-1058.
[23] Chaudhary K, Phadke G, Nistala R, et al. The emerging role of biomarkers in diabetic and hypertensive chronic kidney disease[J]. Curr Diab Rep, 2010, 10(1):37-42.
[24] Pi J, Bai Y, Daniel KW, et al. Persistent oxidative stress due to absence of uncoupling protein 2 associated with impaired pancreatic beta-cell function[J]. Endocrinology, 2009, 150(7):3040-3048.
[25] Kanter M, Uysal H, Karaca T, et al. Depression of glucose levels and partial restoration of pancreatic beta-cell damage by melatonin in streptozotocin-induced diabetic rats[J]. Arch Toxicol, 2006, 80(6):362-369.
[26] Garcia-Maurino S, Pozo D, Calvo JR, et al. Correlation between nuclear melatonin receptor expression and enhanced cytokine production in human lymphocytic and monocytic cell lines[J]. J Pineal Res, 2000, 29(3):129-137.
[27] Parving HH, Lehnert H, Brochner-Mortensen J, et al., and the Irbesartan in Patients with Type 2 Diabetes and Microalbuminuria Study Group. The effect of irbesartan on the development of diabetic nephropathy in patients with type 2 diabetes[J]. N Engl J Med, 2001, 345(12):870-878.
[28] Anwer T. Melatonin ameliorates hyperinsulinemia, glucose intolerance and insulin resistance in stz-nicotinamide induced type 2 diabetic rats[J]. Int J Pharm Pharm Sci, 2014, 6:133-136.
[29] Shibata S, Nagase M,Yoshida S,et al. Podocyte as the target for aldosterone:roles of oxidative stress and Sgkl[J]. Hypertension, 2007, 49(2):355-364.
[30] Kirkali G, Gezer S, Umur N. Nitric oxide in chronic liver disease[J]. Turk J Med Sci, 2000, 30:511-515.
[31] Vaidya VS, Niewczas MA, Ficociello LH, et al. Regression of microalbuminuria in type 1 diabetes is associated with lower levels of urinary tubular injury biomarkers, kidney injury molecule-1, and N-acetyl-β-D-glucosaminidase[J]. Kidney Int,2011,79(4):464-470.
[32] Barutta F, Pinach S, Giunti S, et al. Heat shock protein expression in diabetic nephropathy[J]. Am J Physiol Renal Physiol, 2008, 295(6):F1817-F1824.
[33] Frances DE, Ronco MT, Monti JA, et al. Hyperglycemia induces apoptosis in rat liver through the increase of hydroxyl radical:new insights into the insulin effect[J]. J Endocrinol,2010, 205(2):187-200.
[34] Leonarduzzi G, Scavazza A, Biasi F, et al. The lipid peroxidation end product 4-hydroxy-2,3-nonenal up-regulates transforming growth factor beta-1-expression in the macrophage lineage. A link between oxidative energy and fibrosclerosis[J]. FASEB, 1997, J11:851-857.
[35] Woods JA, Young AJ, Gilmore IT, et al. Measurement of menadione-mediated DNA damage in human lymphocytes using the comet assay[J]. Free Radic Res, 1997, 26(2):113-124.
[36] Shaffie NM, Morsy FA, Ali AG, Sharaf HA. Effect of craway,coriander and fennel on the structure of kidney and islets of langerhan in alloxan-induced diabetic rats[J]. Histol Histochem Study Res, 2010, 2:27-40.
[37] Eliakim-Ikechukwu CF, Obri AI. Histological changes in the pancreas following administration of ethanolic extract of Alchornea cordifolia leaf in alloxan-induced diabetic Wistar rats[J]. Niger J Physiol Sci, 2009, 24(2):153-155.
[2] Moe OW, Berry CA, Rector FCJr. Renal Transport of Glucose,Amino Acids, Sodium, Chloride, and Water in the Kidney[M].Edited by Brenner BM. Philadelphia, USA:W.B. Saunders;2000; 375-415.
[3] Sternberg M, Cohen-Forterre L, Peyroux J. Connective tissue in diabetes mellitus:biochemical alterations of the intercellular matrix with special reference to proteoglycans, collagens and basement membranes[J]. Diabete Metab, 1985, 11(1):27-50.
[4] Bolton WK, Sturgill BC. Spontaneous glomerular sclerosis in aging Sprague-Dawley rats. II. Ultrastructural studies[J]. Am J Pathol, 1980, 98(2):339-356.
[5] Zafar M, Naqvi SNU. Effects of STZ-Induced diabetes on the relative weights of kidney, liver and pancreas in albino rats:a comparative study[J]. Int JMorphol, 2010, 28(1):135-142.
[6] Fadillioglu E, Kurcer Z, Parlakpinar H, et al. Melatonin treatment against remote organ injury induced by renal ischemia reperfusion injury in diabetes mellitus[J]. Arch Pharm Res, 2008, 31(6):705-712.
[7] Magee PN, Swann PF. Nitroso compounds[J]. Br Med Bull,1969, 25(3):240-244.
[8] Winiarska K, Fraczyk T, Malinska D, et al. Melatonin attenuates diabetes-induced oxidative stress in rabbits[J]. J Pineal Res,2006, 40(2):168-176.
[9] Sudnikovich EJ, Maksimchik YZ, Zabrodskaya SV, et al.Melatonin attenuates metabolic disorders due to streptozotocininduced diabetes in rats[J]. Eur J Pharmacol, 2007, 569(3):180-187.
[10] Robeva R, Kirilov G, Tomova A, et al. Melatonin-insulin interactions in patients with metabolic syndrome[J]. J Pineal Res, 2008, 44(1):52-56.
[11] Cam M, Yavuz O, Guven A, et al. Protective effects of chronic melatonin treatment against renal injury in streptozotocininduced diabetic rats[J]. J Pineal Res, 2003, 35(3):212-220.
[12] Thorsten B. Preclinical and clinical overview of terpenes in thetreatment of urolithiasis[J]. Eur Urol, 2010, 9:801-826.
[13] Punithavathi VR, Anuthama R, Prince PS. Combined treatment with naringin and vitamin C ameliorates streptozotocin-induced diabetes in male Wistar rats[J]. J Appl Toxicol, 2008, 28(6):806-813.
[14] Bhandari U, Kanojia R, Pillai KK. Effect of ethanolic extract of Zingiber officinale on dyslipidaemia in diabetic rats[J]. J Ethnopharmacol, 2005, 97(2):227-230.
[15] Yavuz O, Cam M, Bukan N, et al. Protective effect of melatonin onβ-cell damage in streptozotocin-induced diabetes in rats[J].Acta Histochem, 2003, 105(3):261-266.
[16] Romics I, Siller G, Kohnen R, et al. A special terpene combination(Rowatinex(?))improves stone clearance after extracorporeal shockwave lithotripsy in urolithiasis patients:results of a placebo-controlled randomised controlled trial[J].UrolInt, 2011, 86(1):102-109.
[17] Buege JA, Aust SD. Microsomal lipid peroxidation[J]. Methods Enzymol, 1978, 52:302-310.
[18] Moron MS, Depierre JW, Mannervik B. Levels of glutathione,glutathione reductase and glutathione S-transferase activities in rat lung and liver[J]. Biochim Biophys Acta, 1979, 582(1):67-78.
[19] Nishikimi M, Appaji N, Yagi K. The occurrence of superoxide anion in the reaction of reduced phenazine methosulfate and molecular oxygen[J]. Biochem Biophys Res Commun, 1972,46(2):849-854.
[20] Moshage H, Kok B, Huizenga JR, et al. Nitrite and nitrate determinations in plasma:a critical evaluation[J]. Clin Chem,1995,41(6 Pt 1):892-896.
[21] Bradford MM. A rapid and sensitive method for the quantitation of microgram quantities of protein utilizing the principle of protein-dye binding[J]. Anal Biochem, 1976, 72:248-254.
[22] Suzuki H, Suzuki K. Rat hypoplastic kidney(hpk/hpk)induces renal anemia, hyperparathyroidism, and osteodystrophy at the end stage of renal failure[J].J Vet Med Sci,1998,60(10):1051-1058.
[23] Chaudhary K, Phadke G, Nistala R, et al. The emerging role of biomarkers in diabetic and hypertensive chronic kidney disease[J]. Curr Diab Rep, 2010, 10(1):37-42.
[24] Pi J, Bai Y, Daniel KW, et al. Persistent oxidative stress due to absence of uncoupling protein 2 associated with impaired pancreatic beta-cell function[J]. Endocrinology, 2009, 150(7):3040-3048.
[25] Kanter M, Uysal H, Karaca T, et al. Depression of glucose levels and partial restoration of pancreatic beta-cell damage by melatonin in streptozotocin-induced diabetic rats[J]. Arch Toxicol, 2006, 80(6):362-369.
[26] Garcia-Maurino S, Pozo D, Calvo JR, et al. Correlation between nuclear melatonin receptor expression and enhanced cytokine production in human lymphocytic and monocytic cell lines[J]. J Pineal Res, 2000, 29(3):129-137.
[27] Parving HH, Lehnert H, Brochner-Mortensen J, et al., and the Irbesartan in Patients with Type 2 Diabetes and Microalbuminuria Study Group. The effect of irbesartan on the development of diabetic nephropathy in patients with type 2 diabetes[J]. N Engl J Med, 2001, 345(12):870-878.
[28] Anwer T. Melatonin ameliorates hyperinsulinemia, glucose intolerance and insulin resistance in stz-nicotinamide induced type 2 diabetic rats[J]. Int J Pharm Pharm Sci, 2014, 6:133-136.
[29] Shibata S, Nagase M,Yoshida S,et al. Podocyte as the target for aldosterone:roles of oxidative stress and Sgkl[J]. Hypertension, 2007, 49(2):355-364.
[30] Kirkali G, Gezer S, Umur N. Nitric oxide in chronic liver disease[J]. Turk J Med Sci, 2000, 30:511-515.
[31] Vaidya VS, Niewczas MA, Ficociello LH, et al. Regression of microalbuminuria in type 1 diabetes is associated with lower levels of urinary tubular injury biomarkers, kidney injury molecule-1, and N-acetyl-β-D-glucosaminidase[J]. Kidney Int,2011,79(4):464-470.
[32] Barutta F, Pinach S, Giunti S, et al. Heat shock protein expression in diabetic nephropathy[J]. Am J Physiol Renal Physiol, 2008, 295(6):F1817-F1824.
[33] Frances DE, Ronco MT, Monti JA, et al. Hyperglycemia induces apoptosis in rat liver through the increase of hydroxyl radical:new insights into the insulin effect[J]. J Endocrinol,2010, 205(2):187-200.
[34] Leonarduzzi G, Scavazza A, Biasi F, et al. The lipid peroxidation end product 4-hydroxy-2,3-nonenal up-regulates transforming growth factor beta-1-expression in the macrophage lineage. A link between oxidative energy and fibrosclerosis[J]. FASEB, 1997, J11:851-857.
[35] Woods JA, Young AJ, Gilmore IT, et al. Measurement of menadione-mediated DNA damage in human lymphocytes using the comet assay[J]. Free Radic Res, 1997, 26(2):113-124.
[36] Shaffie NM, Morsy FA, Ali AG, Sharaf HA. Effect of craway,coriander and fennel on the structure of kidney and islets of langerhan in alloxan-induced diabetic rats[J]. Histol Histochem Study Res, 2010, 2:27-40.
[37] Eliakim-Ikechukwu CF, Obri AI. Histological changes in the pancreas following administration of ethanolic extract of Alchornea cordifolia leaf in alloxan-induced diabetic Wistar rats[J]. Niger J Physiol Sci, 2009, 24(2):153-155.