Carnosine prevents apoptosis of glomerular cells and podocyte loss in STZ diabetic rats. 2011

Eva Riedl, and Frederick Pfister, and Margarita Braunagel, and Paul Brinkkötter, and Paula Sternik, and Martina Deinzer, and Stephan J L Bakker, and Rob H Henning, and Jacob van den Born, and Bernhard K Krämer, and Gerjan Navis, and Hans-Peter Hammes, and Benito Yard, and Hannes Koeppel
5th Medical Clinic, University Medicine Mannheim, Medical Faculty Mannheim, Heidelberg University, Mannheim, Germany.

OBJECTIVE We identified carnosinase-1 (CN-1) as risk-factor for diabetic nephropathy (DN). Carnosine, the substrate for CN-1, supposedly is a protective factor regarding diabetic complications. In this study, we hypothesized that carnosine administration to diabetic rats might protect the kidneys from glomerular apoptosis and podocyte loss. METHODS We examined the effect of oral L-carnosine administration (1g/kg BW per day) on apoptosis, podocyte loss, oxidative stress, AGEs and hexosamine pathway in kidneys of streptozotocin-induced diabetic Wistar rats after 3 months of diabetes and treatment. RESULTS Hyperglycemia significantly reduced endogenous kidney carnosine levels. In parallel, podocyte numbers significantly decreased (-21% compared to non-diabetics, p<0.05), apoptotic glomerular cells numbers increased (32%, compared to non-diabetic, p<0.05) and protein levels of bax and cytochrome c increased (175% and 117%). Carnosine treatment restored carnosine kidney levels, prevented podocytes loss (+23% compared to diabetic, p<0.05), restrained glomerular apoptosis (-34% compared to diabetic; p<0.05) and reduced expression of bax and cytochrome c (-63% and -54% compared to diabetics, both p<0.05). In kidneys of all diabetic animals, levels of ROS, AGEs and GlcNAc-modified proteins were increased. CONCLUSIONS By inhibition of pro-apoptotic signaling and independent of biochemical abnormalities, carnosine protects diabetic rat kidneys from apoptosis and podocyte loss.

UI MeSH Term Description Entries
D007678 Kidney Glomerulus A cluster of convoluted capillaries beginning at each nephric tubule in the kidney and held together by connective tissue. Glomerulus, Kidney
D002336 Carnosine A naturally occurring dipeptide neuropeptide found in muscles. Carnosine Hydrochloride,Carnosine, (D-His)-Isomer,L-Carnosine,beta-Alanylhistidine,Hydrochloride, Carnosine,L Carnosine,beta Alanylhistidine
D003921 Diabetes Mellitus, Experimental Diabetes mellitus induced experimentally by administration of various diabetogenic agents or by PANCREATECTOMY. Alloxan Diabetes,Streptozocin Diabetes,Streptozotocin Diabetes,Experimental Diabetes Mellitus,Diabete, Streptozocin,Diabetes, Alloxan,Diabetes, Streptozocin,Diabetes, Streptozotocin,Streptozocin Diabete
D004195 Disease Models, Animal Naturally-occurring or experimentally-induced animal diseases with pathological processes analogous to human diseases. Animal Disease Model,Animal Disease Models,Disease Model, Animal
D000117 Acetylglucosamine The N-acetyl derivative of glucosamine. Acetyl Glucosamine,N-Acetyl Glucosamine,N-Acetyl-beta-D-Glucosamine,N-Acetylglucosamine,beta-N-Acetylglucosamine,2-Acetamido-2-Deoxy-D-Glucose,2-Acetamido-2-Deoxyglucose,N-Acetyl-D-Glucosamine,2 Acetamido 2 Deoxy D Glucose,2 Acetamido 2 Deoxyglucose,Glucosamine, Acetyl,Glucosamine, N-Acetyl,N Acetyl D Glucosamine,N Acetyl Glucosamine,N Acetyl beta D Glucosamine,N Acetylglucosamine,beta N Acetylglucosamine
D000284 Administration, Oral The giving of drugs, chemicals, or other substances by mouth. Drug Administration, Oral,Administration, Oral Drug,Oral Administration,Oral Drug Administration,Administrations, Oral,Administrations, Oral Drug,Drug Administrations, Oral,Oral Administrations,Oral Drug Administrations
D000818 Animals Unicellular or multicellular, heterotrophic organisms, that have sensation and the power of voluntary movement. Under the older five kingdom paradigm, Animalia was one of the kingdoms. Under the modern three domain model, Animalia represents one of the many groups in the domain EUKARYOTA. Animal,Metazoa,Animalia
D013311 Streptozocin An antibiotic that is produced by Stretomyces achromogenes. It is used as an antineoplastic agent and to induce diabetes in experimental animals. Streptozotocin,2-Deoxy-2-((methylnitrosoamino)carbonyl)amino-D-glucose,Streptozotocine,Zanosar
D017127 Glycation End Products, Advanced A heterogeneous group of compounds derived from rearrangements, oxidation, and cross-linking reactions that follow from non-enzymatic glycation of amino groups in PROTEINS; LIPIDS; or NUCLEIC ACIDS. Their accumulation in vivo accelerates under hyperglycemic, oxidative, or inflammatory conditions. Heat also accelerates the formation of advanced glycation end products (AGEs) such seen with the browning of food during cooking. Advanced Glycation End Product,Advanced Glycation Endproduct,Advanced Maillard Reaction End Product,Glycated Lipids,Glycotoxins,Maillard Product,Maillard Reaction End Product,Maillard Reaction Product,Advanced Glycation End Products,Advanced Glycation Endproducts,Advanced Maillard Reaction End Products,Glycation Endproducts, Advanced,Maillard Products,Maillard Reaction End Products,Maillard Reaction Products,Glycation Endproduct, Advanced,Lipids, Glycated,Product, Maillard Reaction,Products, Maillard,Products, Maillard Reaction,Reaction Products, Maillard
D017208 Rats, Wistar A strain of albino rat developed at the Wistar Institute that has spread widely at other institutions. This has markedly diluted the original strain. Wistar Rat,Rat, Wistar,Wistar Rats

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