Open Access Open Access  Restricted Access Subscription Access
Open Access Open Access Open Access  Restricted Access Restricted Access Subscription Access

Oxidative Stress Induced Diabetic Nephropathy


Affiliations
1 Department of Pharmacology, J.S.S. College of Pharmacy, (Off campus of JSS University, Mysore), Ooty–643 001, India
2 Department of Pharmacology, J.S.S College of Pharmacy, (Off campus of JSS University, Mysore) Ooty, Niligiris-643001, India
     

   Subscribe/Renew Journal


Diabetic nephropathy is one of the main causes of renal end-stage disease. Morphologically, the development of diabetic nephropathy is characterized by progressive thickening of the glomerular basement membrane and by expansion of the mesangial matrix which correlates to glomerular filtration function. Hyperglycemia generates more reactive oxygen species and also attenuates antioxidative mechanisms through glycation of the scavenging enzymes. Therefore, oxidative stress has been considered to be a common pathogenetic factor of the diabetic complications including nephropathy. A causal relationship between oxidative stress and diabetic nephropathy has been established by observations that (1) Lipid peroxides and 8-hydroxydeoxyguanosine, indices of oxidative tissue injury, were increased in the kidneys of diabetic rats with albuminuria.(2) High glucose directly increases oxidative stress in glomerular mesangial cells, a target cell of diabetic nephropathy.(3) oxidative stress induces mRNA expression of TGFb1( transforming growth factor beta1) and fibronectin which are the genes implicated in diabetic glomerular injury, and (4) Inhibition of oxidative stress ameliorates all the manifestations associated with diabetic nephropathy.

Keywords

Diabetic Nephropathy, Extracellular Matrix, High Glucose, Oxidative Stress.
Subscription Login to verify subscription
User
Notifications
Font Size


  • American Diabetes Association (ADA). Standards of Medical Care in Diabetes—2009. Diabetes Care. January 2009; 32:S13- S61.
  • Z. Mokini, F. Chiarelli, The molecular basis of diabetic microangiopathy, Pediatr. Endocrinol. Rev. 4 (2006) 138–152.
  • H. Sies, Oxidative stress: Introduction, in: H. Sies (Ed.), Oxidative Stress; Oxidants and Antioxidants, Academic Press, London, 1991, pp. xv–xxii.
  • L. Baud, L. Ardaillou, Reactive oxygen species: Production and role in the kidney, Am. J. Physiol. 251 (1986) F765–F776.
  • S.V. Shah, Role of reactive oxygen metabolites in experimental glomerular disease, Kidney Int. 35 (1989) 1093– 1106.
  • J.R. Diamond, The role of reactive oxygen metabolites in animal models of glomerular disease, Am. J. Kidney Dis.19 (1992) 292–300.
  • K.A. Nath.et al., The role of oxidants in progressive renal injury, Kidney Int. 45 (Suppl. 45) (1994) S111–S115.
  • K.A. Nath, A.K. Salahudeen, Introduction of renal growth and injury in the intact rat kidney by dietary deficiency of antioxidants, J. Clin. Invest. 86 (1990) 1179–1192.
  • P. Reichard. .et al., The effect of long-term intensified insulin treatment on the development of microvascular complications of diabetes mellitus, New Engl. J. Med. 329 (1993) 304–309.
  • The Diabetes Control and Complications Trial Research Group, The effect of intensive treatment of diabetes on the development and progression of long-term complication in insulin-dependent diabetes mellitus, New Engl. J. Med. 329 (1993) 977–986.
  • J.W. Baynes, Role of oxidative stress in development of complications in diabetes, Diabetes 40 (1991) 405–412.
  • S.P. Wolff, .et al., Protein glycation and oxidative stress in diabetes mellitus and aging, Free Radic. Biol. Med. 10 (1991) 339–352.
  • S.P. Wolff, Diabetes mellitus and free radicals, Br. Med. Bull. 49 (1993) 642–652.
  • R.G. Larkins, M.E. Dunlop, The link between hyperglycemia and diabetic nephropathy, Diabetologia 35 (1992) 499–504.
  • Hunjoo Ha *, Kyung Hwan Kim; Pathogenesis of diabetic nephropathy: the role of oxidative stress and protein kinase C ; Diabetes Research and Clinical Practice 45 (1999) 147–151.
  • G.L. King.et al., Diabetic vascular dysfunctions: A model of excessive activation of protein kinase C, Kidney Int. 52 (Suppl. 60) (1997) S77–S85.
  • P.A. Craven, F.R. DeRubertis, Protein kinase C is activated in glomeruli from streptozocin diabetic rats: Possible mediation by glucose, J. Clin. Invest. 83 (1989) 1667–1675.
  • P.A. Craven.et al., Increase in diacylglycerol mass in isolated glomeruli by glucose from de novo synthesis or glycerolipids, Diabetes 39 (1990) 667–674.
  • S.V. Sah, Light emission by isolated rat glomeruli in response to phorbol myristate acetate, J. Lab. Clin. Med. 98 (1981) 46–56.
  • A. Myanoshita.et al.Inhibitory effect of cyclic AMP on phorbolstimulated production of reactive oxygen metabolites in rat glomeruli, Biochem. Biophys. Res. Commun. 30 (1989) 519–525
  • H. Ha, H. Endou, Lipid peroxidation in isolated rat nephron segments, Am. J. Physiol. 263 (1992) F201– F207.
  • H. Ha, K.H. Kim, Role of protein kinase C-mediated oxidative stress in increased TGF-b1 and fibronectin mRNAs in mesangial cells: Implications for diabetic nephropathy (abstract), Nephrology 3 (Suppl. 1) (1997) A736.
  • M. Brownlee.et al., Advanced glycosylation end products in tissue and the biochemical basis of diabetic complications, New Engl. J. Med. 318 (1988) 1315–1321.
  • H. Vlassara, Recent progress in advanced glycation end products and diabetic complications, Diabetes 46 (Suppl. 2) (1997) S19–S25.
  • H.B. Lee.et al., Pathogenic role of advanced glycosylation end products in diabetic nephropathy, Kidney Int. 52 (Suppl. 60) (1997) S60–S65.
  • S.D. Yan.et al., Enhanced cellular oxidant stress by the interaction of advanced glycosylation end products with their receptors: binding proteins, J. Biol. Chem. 269 (1994) 9889– 9897.
  • J.L. Wautier.et al., Receptor mediated endothelial dysfunction in diabetic vasculopathy: s RAGE blocks hyperpermeability, J. Clin. Invest. 97 (1996) 238–243.
  • A.K. Salahudeen.et al., Pathogenesis of diabetic nephropathy: a radical approach, Nephrol. Dial. Transplant. 12 (1997) 664–668.
  • H. Ha, V.S. Kamanna.et al., Role of glycated low density lipoprotein in mesangial extracellular matrix synthesis, Kidney Int. 52 (Suppl. 60) (1997) S54–S59.

Abstract Views: 228

PDF Views: 0




  • Oxidative Stress Induced Diabetic Nephropathy

Abstract Views: 228  |  PDF Views: 0

Authors

R. Vadivelan
Department of Pharmacology, J.S.S. College of Pharmacy, (Off campus of JSS University, Mysore), Ooty–643 001, India
P. Umasankar
Department of Pharmacology, J.S.S College of Pharmacy, (Off campus of JSS University, Mysore) Ooty, Niligiris-643001, India
Dipanjan Mandal
Department of Pharmacology, J.S.S College of Pharmacy, (Off campus of JSS University, Mysore) Ooty, Niligiris-643001, India
A. Shanish
Department of Pharmacology, J.S.S College of Pharmacy, (Off campus of JSS University, Mysore) Ooty, Niligiris-643001, India
S. P. Dhanabal
Department of Pharmacology, J.S.S College of Pharmacy, (Off campus of JSS University, Mysore) Ooty, Niligiris-643001, India
K. Elango
Department of Pharmacology, J.S.S College of Pharmacy, (Off campus of JSS University, Mysore) Ooty, Niligiris-643001, India

Abstract


Diabetic nephropathy is one of the main causes of renal end-stage disease. Morphologically, the development of diabetic nephropathy is characterized by progressive thickening of the glomerular basement membrane and by expansion of the mesangial matrix which correlates to glomerular filtration function. Hyperglycemia generates more reactive oxygen species and also attenuates antioxidative mechanisms through glycation of the scavenging enzymes. Therefore, oxidative stress has been considered to be a common pathogenetic factor of the diabetic complications including nephropathy. A causal relationship between oxidative stress and diabetic nephropathy has been established by observations that (1) Lipid peroxides and 8-hydroxydeoxyguanosine, indices of oxidative tissue injury, were increased in the kidneys of diabetic rats with albuminuria.(2) High glucose directly increases oxidative stress in glomerular mesangial cells, a target cell of diabetic nephropathy.(3) oxidative stress induces mRNA expression of TGFb1( transforming growth factor beta1) and fibronectin which are the genes implicated in diabetic glomerular injury, and (4) Inhibition of oxidative stress ameliorates all the manifestations associated with diabetic nephropathy.

Keywords


Diabetic Nephropathy, Extracellular Matrix, High Glucose, Oxidative Stress.

References