The carbonyl scavenger carnosine ameliorates dyslipidaemia and renal function in Zucker obese rats.
The metabolic syndrome is a risk factor that increases the risk for development of renal and vascular complications. This study addresses the effects of chronic administration of the endogenous dipeptide carnosine (β-alanyl-L-histidine, L-CAR) and of its enantiomer (β-alanyl-D-histidine, D-CAR) on hyperlipidaemia, hypertension, advanced glycation end products, advanced lipoxidation end products formation and development of nephropathy in the non-diabetic, Zucker obese rat. The Zucker rats received a daily dose of L-CAR or D-CAR (30 mg/kg in drinking water) for 24 weeks. Systolic blood pressure was recorded monthly. At the end of the treatment, plasma levels of triglycerides, total cholesterol, glucose, insulin, creatinine and urinary levels of total protein, albumin and creatinine were measured. Several indices of oxidative/carbonyl stress were also measured in plasma, urine and renal tissue. We found that both L- and D-CAR greatly reduced obese-related diseases in obese Zucker rat, by significantly restraining the development of dyslipidaemia, hypertension and renal injury, as demonstrated by both urinary parameters and electron microscopy examinations of renal tissue. Because the protective effect elicited by L- and D-CAR was almost superimposable, we conclude that the pharmacological action of L-CAR is not due to a pro-histaminic effect (D-CAR is not a precursor of histidine, since it is stable to peptidic hydrolysis), and prompted us to propose that some of the biological effects can be mediated by a direct carbonyl quenching mechanism.
Aldini
Giancarlo
G
Department of Pharmaceutical Sciences Pietro Pratesi, Università degli Studi di Milano, Milan, Italy. giancarlo.aldini@unimi.it
Orioli
Marica
M
Rossoni
Giuseppe
G
Savi
Federica
F
Braidotti
Paola
P
Vistoli
Giulio
G
Yeum
Kyung-Jin
KJ
Negrisoli
Gianpaolo
G
Carini
Marina
M
D000284:Administration, Oral; D000418:Albumins / Q000032:analysis; D000818:Animals; D001786:Blood Glucose / Q000032:analysis; D001794:Blood Pressure / Q000187:drug effects; D002336:Carnosine / Q000494:pharmacology* / Q000627:therapeutic use; D002784:Cholesterol / Q000097:blood; D003404:Creatinine / Q000652:urine; D016166:Free Radical Scavengers / Q000494:pharmacology* / Q000627:therapeutic use; D017127:Glycation End Products, Advanced / Q000097:blood / Q000652:urine; D006949:Hyperlipidemias / Q000150:complications / Q000188:drug therapy*; D006973:Hypertension / Q000150:complications; D007328:Insulin / Q000097:blood; D007668:Kidney / Q000473:pathology; D007677:Kidney Function Tests; D024821:Metabolic Syndrome / Q000097:blood* / Q000150:complications / Q000503:physiopathology / Q000652:urine*; D009765:Obesity / Q000097:blood* / Q000150:complications / Q000503:physiopathology / Q000652:urine*; D018384:Oxidative Stress / Q000187:drug effects; D051381:Rats; D011924:Rats, Zucker; D013237:Stereoisomerism; D014280:Triglycerides / Q000097:blood
D000418:Albumins; D001786:Blood Glucose; D016166:Free Radical Scavengers; D017127:Glycation End Products, Advanced; D007328:Insulin; D014280:Triglycerides; D002336:Carnosine; D002784:Cholesterol; D003404:Creatinine