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Metformin attenuates streptozotocin-induced diabetic nephropathy in rats through modulation of oxidative stress genes expression.
Chem Biol Interact. 2011 Jul 15; 192(3):233-42.CB

Abstract

Diabetes mellitus is a group of metabolic diseases characterized by hyperglycemia resulting from defects in insulin secretion and/or action. One of the most important complications of this metabolic disease is diabetic nephropathy. Hyperglycemia promotes oxidative stress and hence generation of reactive oxygen species (ROS), which is known to play a crucial role in the pathogenesis of diabetic nephropathy. Recent studies have established that metformin, an oral hypoglycemic drug, possesses antioxidant effects. However, whether metformin can protect against diabetic nephropathy has not been reported before. The overall objectives of the present study are to elucidate the potential nephroprotective effect of metformin in a rat diabetic nephropathy model and explore the exact underlying mechanism(s) involved. The effect of metformin on the biochemical changes associated with hyperglycemia induced by streptozotocin was investigated in rat kidney tissues. In addition, energy nucleotides (AMP and ATP), and Acetyl-CoA in the kidney homogenates and mitochondria, and the mRNA expression of oxidative stress and pro-inflammatory mediators were assessed. Our results showed that treatment of normoglycemic rats with metformin caused significant increase in ATP, Acetyl-CoA, and CoA-SH contents in kidney homogenates and mitochondria along with profound decrease in AMP level. On the other hand, treatment of diabetic nephropathy rats with metformin normalized all biochemical changes and the energy status in kidney tissues. At the transcriptional levels, metformin treatment caused significant restoration in diabetic nephropathy-induced oxidative stress mRNA levels, particularly GSTα, NQO1, and CAT genes, whereas inhibited TNF-α and IL-6 pro-inflammatory genes. Our data lend further credence for the contribution of metformin in the nephroprotective effect in addition to its well known hypoglycemic action.

Authors+Show Affiliations

Department of Pharmacology, College of Medicine, King Saud University, Riyadh, Saudi Arabia. aqahaider@hotmail.comNo affiliation info availableNo affiliation info availableNo affiliation info availableNo affiliation info availableNo affiliation info available

Pub Type(s)

Journal Article
Research Support, Non-U.S. Gov't

Language

eng

PubMed ID

21457706

Citation

Alhaider, Abdulqader A., et al. "Metformin Attenuates Streptozotocin-induced Diabetic Nephropathy in Rats Through Modulation of Oxidative Stress Genes Expression." Chemico-biological Interactions, vol. 192, no. 3, 2011, pp. 233-42.
Alhaider AA, Korashy HM, Sayed-Ahmed MM, et al. Metformin attenuates streptozotocin-induced diabetic nephropathy in rats through modulation of oxidative stress genes expression. Chem Biol Interact. 2011;192(3):233-42.
Alhaider, A. A., Korashy, H. M., Sayed-Ahmed, M. M., Mobark, M., Kfoury, H., & Mansour, M. A. (2011). Metformin attenuates streptozotocin-induced diabetic nephropathy in rats through modulation of oxidative stress genes expression. Chemico-biological Interactions, 192(3), 233-42. https://doi.org/10.1016/j.cbi.2011.03.014
Alhaider AA, et al. Metformin Attenuates Streptozotocin-induced Diabetic Nephropathy in Rats Through Modulation of Oxidative Stress Genes Expression. Chem Biol Interact. 2011 Jul 15;192(3):233-42. PubMed PMID: 21457706.
* Article titles in AMA citation format should be in sentence-case
TY - JOUR T1 - Metformin attenuates streptozotocin-induced diabetic nephropathy in rats through modulation of oxidative stress genes expression. AU - Alhaider,Abdulqader A, AU - Korashy,Hesham M, AU - Sayed-Ahmed,Mohamed M, AU - Mobark,Mohammed, AU - Kfoury,Hala, AU - Mansour,Mahmoud A, Y1 - 2011/03/30/ PY - 2010/12/25/received PY - 2011/03/22/revised PY - 2011/03/23/accepted PY - 2011/4/5/entrez PY - 2011/4/5/pubmed PY - 2011/7/26/medline SP - 233 EP - 42 JF - Chemico-biological interactions JO - Chem Biol Interact VL - 192 IS - 3 N2 - Diabetes mellitus is a group of metabolic diseases characterized by hyperglycemia resulting from defects in insulin secretion and/or action. One of the most important complications of this metabolic disease is diabetic nephropathy. Hyperglycemia promotes oxidative stress and hence generation of reactive oxygen species (ROS), which is known to play a crucial role in the pathogenesis of diabetic nephropathy. Recent studies have established that metformin, an oral hypoglycemic drug, possesses antioxidant effects. However, whether metformin can protect against diabetic nephropathy has not been reported before. The overall objectives of the present study are to elucidate the potential nephroprotective effect of metformin in a rat diabetic nephropathy model and explore the exact underlying mechanism(s) involved. The effect of metformin on the biochemical changes associated with hyperglycemia induced by streptozotocin was investigated in rat kidney tissues. In addition, energy nucleotides (AMP and ATP), and Acetyl-CoA in the kidney homogenates and mitochondria, and the mRNA expression of oxidative stress and pro-inflammatory mediators were assessed. Our results showed that treatment of normoglycemic rats with metformin caused significant increase in ATP, Acetyl-CoA, and CoA-SH contents in kidney homogenates and mitochondria along with profound decrease in AMP level. On the other hand, treatment of diabetic nephropathy rats with metformin normalized all biochemical changes and the energy status in kidney tissues. At the transcriptional levels, metformin treatment caused significant restoration in diabetic nephropathy-induced oxidative stress mRNA levels, particularly GSTα, NQO1, and CAT genes, whereas inhibited TNF-α and IL-6 pro-inflammatory genes. Our data lend further credence for the contribution of metformin in the nephroprotective effect in addition to its well known hypoglycemic action. SN - 1872-7786 UR - https://www.unboundmedicine.com/medline/citation/21457706/Metformin_attenuates_streptozotocin_induced_diabetic_nephropathy_in_rats_through_modulation_of_oxidative_stress_genes_expression_ L2 - https://linkinghub.elsevier.com/retrieve/pii/S0009-2797(11)00120-7 DB - PRIME DP - Unbound Medicine ER -