The carbonyl scavenger carnosine ameliorates dyslipidaemia and renal function in Zucker obese rats.
Bottom Line: 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.
Affiliation: Department of Pharmaceutical Sciences Pietro Pratesi, Università degli Studi di Milano, Milan, Italy. firstname.lastname@example.orgShow MeSH
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Mentions: Figure 3 reports the PK profiles of L- and D-CAR. Endogenous concentration of L-CAR before the treatment was 0.193 ± 0.04 nmoles/ml. After an oral administration of L-CAR (100 mg/kg), the maximal plasma level of the compound was reached 1 hr after dosing (Cmax 147.7 ± 6.50 nmoles/ml). The plasma concentration declined rapidly and returned to the baseline at 2 hrs after dosing. The half-life of the compound was estimated to be 0.24 ± 0.02 hrs. The systemic exposure up to infinite time was 118.45 ± 9.24 nmoles*hr/ml. The variability (CV%) of the systemic exposures descriptors, Cmax and AUC(0 –∞), was 8.97% and 12.04%, respectively.
Affiliation: Department of Pharmaceutical Sciences Pietro Pratesi, Università degli Studi di Milano, Milan, Italy. email@example.com