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Improving Effects of Melatonin on the Histologic Alterations of Rat Kidneys Induced by Experimental Diabetes

Year 2005, Volume: 12 Issue: 3, 145 - 152, 01.06.2005

Abstract

Objective: This study was designed to investigate the improving effects of melatonin on renal histological alterations in streptozotocin (STZ)- induced diabetic rat model. Material and Metods: Fifteen Sprague-Dawley adult female rats were divided into three groups: control, diabetic (D) and diabetic treatment with melatonin (DM) groups. Experimental diabetes was induced by single dose STZ (45 mg/kg) intraperitoneally. After administration of STZ, the DM group began to receive a 10 mg/kg i.p. dose of melatonin per day. These enjection were continued until the end of the study (8 week). At the end of experimentation, blood glucose levels were determined and following routine tissue process kidneys were embedded in paraffin. Histochemical and immunohistochemical stains were applied and the specimens examined by light microscope. Results: After 8 week, the rats in diabetes group had significantly lower body weight and significantly higher blood glucose levels than the rats of control and DM group. The main histological changes resulting from diabetes were detected in glomerular and tubular basal membrane and epithelial cells (glycogen accumulation, swelling and vacuolization). We observed the positive improving effects of melatonin treatment on these findings. Conclusion: We concluded that chronically administration melatonin reduced renal injury in STZ- induced diabetic rats. Therefore, we believe that melatonin might be used to prevent development of diabetic renal damage. However, further researches are needed on long-term uses of melatonin in order to show its positive effects on diabetic complications. Key words: Experimental diabetes, Melatonin, Kidney, Histological alterations.

References

  • Yenigün M. Her Yönü İle Diabetes Mellitus. Haseki Hastanesi Vakfı Yayını II. 1995:15.
  • Catalano C, Marshall SM. Epidemiology of end-stage renal disease in patients with diabetes mellitus: from thr dark ages to the middle ages. Nephrol Dial Transplant 1992; 7: 181-190.
  • Carl-David A, Stenram U, Torffvit o et al. Effects of inhibition of glycation and oxidative stress on the development of diabetic nephropaty in rats. Journal of Diabetes Its Complications 2002; 16: 395-400.
  • Vural S, Sabuncu T, Arslan SO et al. Melatonin inhibits lipid peroxidation and stimulates the antioxidant status of diabetic rats. J Pineal Res 2001; 31: 193-198.
  • Baydas G, Canatan H, Turkoglu A. Comparative analysis of the protective effects of melatonin and vitamin C on streptozocin-induced diabetes mellitus. J Pineal Res 2002; 32: 225-230.
  • Tan DX, Reiter RJ, Manchester KC et al. Chemical and physical properties and potential mechanism: melatonin as a broad spectrum antioxidant and free radical scavenger. Curr Top Med Chen 2002; 2(2): 181-97.
  • Vijayalaxmi TCR, Reiter RJ, Herman TS. Melatonin: From basic research to cancer treatment clinics. Journal of Clinical Oncology 2002; 20(10): 2575- 2601.
  • Kowluru RA, Abbas SN, Odenbach S. Revesall of hyperglisemia and diabetic nephropaty. Effect of reinstitution of good metabolic control on oxidative stress in the kidney of diabetic rats. Journal of Diabetes and Its Complications 2004; 18: 282- 288.
  • Cam M, Yavuz O, Güven A et al. Protective effects of chronic melatonin treatmant against renal injury in streptozotocin-induced diabetic rats. J Pineal Res 2003; 35:212- 220.
  • Mamdouh Anwar M, Meki Abdel-Rahim MA.Oxidative stress in streptozotocin- induced diabetic rats: effects of garlic oil and melatonin. Comparative Biochemistry and Physiology Part A 2003; 135: 539-547.
  • Aksoy N, Vural H, Sabuncu T et al. Effects of melatonin on oxidative-antioxidative status of tissues in streptozotocin-induced diabetic rats. Cell Biochemistry and Function 2003; 21: 121-125.
  • Andallu B, Varadacharyulu NC. Antioxidant role of mulberry (morus indica L.Cu. Anantha) leaves in streptozotocin-diabetic rats. Clinica Chimica Acta 2003; 338: 3-10.
  • Montilla PL, Vargas JF, Tunez IF et al. Oxidative stress in diabetic rats induced by streptozotocin: Protective effects of melatonin. J Pineal Res 1998; 25: 94-100.
  • Andersson AK, Sandler S. Melatonin protects against streptozotocin, but not interleukin-1β-induced damage of rodent pancreatic B-cell. J Pineal res 2001; 30: 157- 165.
  • Görgün MF, Öztürk Z, Gümüştaş K et al. Melatonin administration effects plasma total sialic acid and lipid peroxidation levels in streptozotocin induced diabetic rats. Journal of Toxicology and Enviromental Health 2002; 65: 695-700.
  • Shima T, Chun SJ, Niijima A et al. Melatonin suppress hyperglisemia caused by intracerebroventricular injection of 2-deoxy-D-glucose in rats. Neuroscience Letters 1997; 226: 119-122.
  • Anhe GF, Caperuto LC, Pereira DS et al. In vivo activation of insulin receptor tyrosine kinase by melatonin in the rat hypothalamus. J Neurochem 2004; 90(3): 559- 66.
  • Maitra SK, Dey M, Dutta S et al. Influences of graded dose of melatonin on the levels of blood glucose and adrenal catecholamines in male roseringed parakeet (Psittacula krameri) under different photoperiods. Arch Physiol Biochem 2000; 108: 444-450.
  • Rao VSN, Santos FA, Silva RM et al. Effects of nitric exide synthase inhibitors and melatonin on the hyperglisemic response to streptozotocin in rats. Vascular Pharmacology 2002; 38: 127-130.
  • Peschke E, Fauteck JD, MuBhoff U et al. Evidence for a melatonin receptor within pancreatic islets of neonate rats: functional, autoradiographic, and molecular investigation. J Pinale Res 2000; 28: 156-164.
  • McCance KL, Huether Se. Pathophysiology The Biologic Basis for Disease in Adults and Children : In: McCane KL. Altered Cellular and Tissue Biology. Second edition. Mosby 1994: 73.
  • Lehman R, Schleicher ED. Molecular mechanism of diabetic nephropaty. Clinica Chimica Acta 2000; 297: 135-144.
  • Oztürk F, Iraz M, Eşrefoğlu M, ve ark. Deneysel diyabetin sıçan böbreklerinde meydana getirdiği histolojik değişiklikler. İnönü Üniversitesi Tıp Fakültesi Dergisi 2005; 12(1): 1-4.
  • Singh LP, Crook ED. Hexosamine regulation of glucose-mediated laminin synthesis in mesangial cells involves proetin kinases A and C. Am J Physiol Renal Physiol 2000; 279: 646-654.
  • Reeves BR, Andreoli TE. Transforming growth factor β contributes to progressive diabetic nephropathy.. PNAS 2000; 97(14): 7667-7669.
  • Ayo SH, Radnik RA, Gloss WF et al. High glucose causes an increase in extracellular matrix proteins in cultured mesangial cells. Am J Pathol 1990; 136: 1339-1348.
  • Catherwood MA, Powell LA, Anderson P et al. Glucose-induced oxidative stress in mesangial cells. Kidney Int 2002; 61: 599-608.
  • HA H, YU MR, KIM KH. Melatonin and taurinereduce early glomerulopathy in diabetic rats. Free Radic Biol Med 1999; 26: 944-950.
  • Gugliucci A. Glycation as the glucose link to diabetic complication. JAOA 2000; 100(10): 621-634.

Deneysel Diyabetin Sıçan Böbreklerinde Meydana Getirdiği Histolojik Değişiklikler Üzerine Melatoninin İyileştirici Etkileri

Year 2005, Volume: 12 Issue: 3, 145 - 152, 01.06.2005

Abstract

Amaç: Bu çalışma, streptozotosin (STZ) ile oluşturulan diyabetik rat modelinde, sıçan böbreklerinde oluşan histolojik değişiklikler üzerine melatoninin iyileştirici etkilerinin araştırılması amacıyla planlandı. Gereç ve Yöntem: Çalışmada kullanılan Spraque-Dawley cinsi; 15 adet erişkin dişi sıçan: kontrol, diyabet (D) ve melatonin ile tedavi edilen diyabet (DM) gruplarına ayrıldı. Deneysel diyabet D ve DM gruplarında tek doz STZ'nin (45 mg/kg) intraperitoneal uygulanması ile oluşturuldu. Diyabet oluşturulduktan sonra, DM grubuna 8 hafta her gün 10 mg/kg melatonin i.p. olarak uygulandı. Deneyin sonunda sıçanların kan-glikoz seviyeleri ölçüldü. Örnekler rutin doku takibinden sonra, parafine gömüldü. Histokimyasal ve immunohistokimyasal boyamaların ardından, kesitler ışık mikroskopta incelendi. Bulgular: Diyabet grubundaki sıçanların, kontrol ve DM grubuna göre kan-glikoz düzeyleri önemli derecede yükselirken, vucut ağırlıkları belirgin şekilde azaldı. Diyabete bağlı olarak gelişen temel histolojik değişiklikler glomerul ve tubül bazal membranları ile epitel hücrelerinde gözlendi. Uygulanan melatonin tedavisiyle, bu bulguların önemli ölçüde hafiflediği tesbit edildi. Sonuç: Kronik melatonin uygulaması STZ ile sıçanlarda oluşturulan diyabetin neden olduğu böbrek hasarını azalttı. Bu yüzden melatoninin diyabetik böbrek hasarının gelişimini önleyeceğini veya bulguları hafifleteceğini düşünmekteyiz. Yine de diyabetik komplikasyonlar üzerindeki pozitif etkisini göstermek için uzun süreli kullanımlar ile ilgili daha ileriki çalışmalara ihtiyaç bulunmaktadır. Anahtar kelimeler: Deneysel diyabet, Melatonin, Böbrek, Histolojik değişiklikler.

References

  • Yenigün M. Her Yönü İle Diabetes Mellitus. Haseki Hastanesi Vakfı Yayını II. 1995:15.
  • Catalano C, Marshall SM. Epidemiology of end-stage renal disease in patients with diabetes mellitus: from thr dark ages to the middle ages. Nephrol Dial Transplant 1992; 7: 181-190.
  • Carl-David A, Stenram U, Torffvit o et al. Effects of inhibition of glycation and oxidative stress on the development of diabetic nephropaty in rats. Journal of Diabetes Its Complications 2002; 16: 395-400.
  • Vural S, Sabuncu T, Arslan SO et al. Melatonin inhibits lipid peroxidation and stimulates the antioxidant status of diabetic rats. J Pineal Res 2001; 31: 193-198.
  • Baydas G, Canatan H, Turkoglu A. Comparative analysis of the protective effects of melatonin and vitamin C on streptozocin-induced diabetes mellitus. J Pineal Res 2002; 32: 225-230.
  • Tan DX, Reiter RJ, Manchester KC et al. Chemical and physical properties and potential mechanism: melatonin as a broad spectrum antioxidant and free radical scavenger. Curr Top Med Chen 2002; 2(2): 181-97.
  • Vijayalaxmi TCR, Reiter RJ, Herman TS. Melatonin: From basic research to cancer treatment clinics. Journal of Clinical Oncology 2002; 20(10): 2575- 2601.
  • Kowluru RA, Abbas SN, Odenbach S. Revesall of hyperglisemia and diabetic nephropaty. Effect of reinstitution of good metabolic control on oxidative stress in the kidney of diabetic rats. Journal of Diabetes and Its Complications 2004; 18: 282- 288.
  • Cam M, Yavuz O, Güven A et al. Protective effects of chronic melatonin treatmant against renal injury in streptozotocin-induced diabetic rats. J Pineal Res 2003; 35:212- 220.
  • Mamdouh Anwar M, Meki Abdel-Rahim MA.Oxidative stress in streptozotocin- induced diabetic rats: effects of garlic oil and melatonin. Comparative Biochemistry and Physiology Part A 2003; 135: 539-547.
  • Aksoy N, Vural H, Sabuncu T et al. Effects of melatonin on oxidative-antioxidative status of tissues in streptozotocin-induced diabetic rats. Cell Biochemistry and Function 2003; 21: 121-125.
  • Andallu B, Varadacharyulu NC. Antioxidant role of mulberry (morus indica L.Cu. Anantha) leaves in streptozotocin-diabetic rats. Clinica Chimica Acta 2003; 338: 3-10.
  • Montilla PL, Vargas JF, Tunez IF et al. Oxidative stress in diabetic rats induced by streptozotocin: Protective effects of melatonin. J Pineal Res 1998; 25: 94-100.
  • Andersson AK, Sandler S. Melatonin protects against streptozotocin, but not interleukin-1β-induced damage of rodent pancreatic B-cell. J Pineal res 2001; 30: 157- 165.
  • Görgün MF, Öztürk Z, Gümüştaş K et al. Melatonin administration effects plasma total sialic acid and lipid peroxidation levels in streptozotocin induced diabetic rats. Journal of Toxicology and Enviromental Health 2002; 65: 695-700.
  • Shima T, Chun SJ, Niijima A et al. Melatonin suppress hyperglisemia caused by intracerebroventricular injection of 2-deoxy-D-glucose in rats. Neuroscience Letters 1997; 226: 119-122.
  • Anhe GF, Caperuto LC, Pereira DS et al. In vivo activation of insulin receptor tyrosine kinase by melatonin in the rat hypothalamus. J Neurochem 2004; 90(3): 559- 66.
  • Maitra SK, Dey M, Dutta S et al. Influences of graded dose of melatonin on the levels of blood glucose and adrenal catecholamines in male roseringed parakeet (Psittacula krameri) under different photoperiods. Arch Physiol Biochem 2000; 108: 444-450.
  • Rao VSN, Santos FA, Silva RM et al. Effects of nitric exide synthase inhibitors and melatonin on the hyperglisemic response to streptozotocin in rats. Vascular Pharmacology 2002; 38: 127-130.
  • Peschke E, Fauteck JD, MuBhoff U et al. Evidence for a melatonin receptor within pancreatic islets of neonate rats: functional, autoradiographic, and molecular investigation. J Pinale Res 2000; 28: 156-164.
  • McCance KL, Huether Se. Pathophysiology The Biologic Basis for Disease in Adults and Children : In: McCane KL. Altered Cellular and Tissue Biology. Second edition. Mosby 1994: 73.
  • Lehman R, Schleicher ED. Molecular mechanism of diabetic nephropaty. Clinica Chimica Acta 2000; 297: 135-144.
  • Oztürk F, Iraz M, Eşrefoğlu M, ve ark. Deneysel diyabetin sıçan böbreklerinde meydana getirdiği histolojik değişiklikler. İnönü Üniversitesi Tıp Fakültesi Dergisi 2005; 12(1): 1-4.
  • Singh LP, Crook ED. Hexosamine regulation of glucose-mediated laminin synthesis in mesangial cells involves proetin kinases A and C. Am J Physiol Renal Physiol 2000; 279: 646-654.
  • Reeves BR, Andreoli TE. Transforming growth factor β contributes to progressive diabetic nephropathy.. PNAS 2000; 97(14): 7667-7669.
  • Ayo SH, Radnik RA, Gloss WF et al. High glucose causes an increase in extracellular matrix proteins in cultured mesangial cells. Am J Pathol 1990; 136: 1339-1348.
  • Catherwood MA, Powell LA, Anderson P et al. Glucose-induced oxidative stress in mesangial cells. Kidney Int 2002; 61: 599-608.
  • HA H, YU MR, KIM KH. Melatonin and taurinereduce early glomerulopathy in diabetic rats. Free Radic Biol Med 1999; 26: 944-950.
  • Gugliucci A. Glycation as the glucose link to diabetic complication. JAOA 2000; 100(10): 621-634.
There are 29 citations in total.

Details

Primary Language Turkish
Journal Section Articles
Authors

Nigar Vardı This is me

Mustafa Iraz This is me

Feral Öztürk This is me

Muharrem Uçar This is me

Mehmet Gül This is me

Mukaddes Eşrefoğlu This is me

Ali Otlu This is me

Publication Date June 1, 2005
Published in Issue Year 2005 Volume: 12 Issue: 3

Cite

APA Vardı, N., Iraz, M., Öztürk, F., Uçar, M., et al. (2005). Deneysel Diyabetin Sıçan Böbreklerinde Meydana Getirdiği Histolojik Değişiklikler Üzerine Melatoninin İyileştirici Etkileri. Journal of Turgut Ozal Medical Center, 12(3), 145-152.
AMA Vardı N, Iraz M, Öztürk F, Uçar M, Gül M, Eşrefoğlu M, Otlu A. Deneysel Diyabetin Sıçan Böbreklerinde Meydana Getirdiği Histolojik Değişiklikler Üzerine Melatoninin İyileştirici Etkileri. J Turgut Ozal Med Cent. June 2005;12(3):145-152.
Chicago Vardı, Nigar, Mustafa Iraz, Feral Öztürk, Muharrem Uçar, Mehmet Gül, Mukaddes Eşrefoğlu, and Ali Otlu. “Deneysel Diyabetin Sıçan Böbreklerinde Meydana Getirdiği Histolojik Değişiklikler Üzerine Melatoninin İyileştirici Etkileri”. Journal of Turgut Ozal Medical Center 12, no. 3 (June 2005): 145-52.
EndNote Vardı N, Iraz M, Öztürk F, Uçar M, Gül M, Eşrefoğlu M, Otlu A (June 1, 2005) Deneysel Diyabetin Sıçan Böbreklerinde Meydana Getirdiği Histolojik Değişiklikler Üzerine Melatoninin İyileştirici Etkileri. Journal of Turgut Ozal Medical Center 12 3 145–152.
IEEE N. Vardı, M. Iraz, F. Öztürk, M. Uçar, M. Gül, M. Eşrefoğlu, and A. Otlu, “Deneysel Diyabetin Sıçan Böbreklerinde Meydana Getirdiği Histolojik Değişiklikler Üzerine Melatoninin İyileştirici Etkileri”, J Turgut Ozal Med Cent, vol. 12, no. 3, pp. 145–152, 2005.
ISNAD Vardı, Nigar et al. “Deneysel Diyabetin Sıçan Böbreklerinde Meydana Getirdiği Histolojik Değişiklikler Üzerine Melatoninin İyileştirici Etkileri”. Journal of Turgut Ozal Medical Center 12/3 (June 2005), 145-152.
JAMA Vardı N, Iraz M, Öztürk F, Uçar M, Gül M, Eşrefoğlu M, Otlu A. Deneysel Diyabetin Sıçan Böbreklerinde Meydana Getirdiği Histolojik Değişiklikler Üzerine Melatoninin İyileştirici Etkileri. J Turgut Ozal Med Cent. 2005;12:145–152.
MLA Vardı, Nigar et al. “Deneysel Diyabetin Sıçan Böbreklerinde Meydana Getirdiği Histolojik Değişiklikler Üzerine Melatoninin İyileştirici Etkileri”. Journal of Turgut Ozal Medical Center, vol. 12, no. 3, 2005, pp. 145-52.
Vancouver Vardı N, Iraz M, Öztürk F, Uçar M, Gül M, Eşrefoğlu M, Otlu A. Deneysel Diyabetin Sıçan Böbreklerinde Meydana Getirdiği Histolojik Değişiklikler Üzerine Melatoninin İyileştirici Etkileri. J Turgut Ozal Med Cent. 2005;12(3):145-52.