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The carbonyl scavenger carnosine ameliorates dyslipidaemia and renal function in Zucker obese rats.

Aldini G, Orioli M, Rossoni G, Savi F, Braidotti P, Vistoli G, Yeum KJ, Negrisoli G, Carini M - J. Cell. Mol. Med. (2010)

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.

View Article: PubMed Central - PubMed

Affiliation: Department of Pharmaceutical Sciences Pietro Pratesi, Università degli Studi di Milano, Milan, Italy. giancarlo.aldini@unimi.it

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Selected Reaction Monitoring (SRM) chromatogram, relative to CAR-HNE parent ion → product ions transition, in LN (A), ZK (B) and Zucker treated animals (ZK + D, C; ZK + L, D) and CAR-HNE structure.
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fig08: Selected Reaction Monitoring (SRM) chromatogram, relative to CAR-HNE parent ion → product ions transition, in LN (A), ZK (B) and Zucker treated animals (ZK + D, C; ZK + L, D) and CAR-HNE structure.

Mentions: By applying a recently developed LC-MS/MS method [14], we have shown that the Michael adduct between CAR and HNE is a stable and reliable biomarker of lipid peroxidation and carbonylation in vivo. By demonstrating higher levels of this adduct in urine from ZK rats compared to LN animals, we confirmed HNE overproduction in obese animals and the role of CAR as an endogenous detoxifying agent of RCS. The same analytical approach was applied in this study to confirm the in vivo RCS-trapping ability of exogenous L- and D-CAR. Figure 8 summarizes these results and shows typical LC-ESI-MS/MS profiles of urine, relative to the four groups of animals, acquired in MRM by setting the precursor ion at m/z 383.1 (CID@40.00 V). As reported in Table 2, the CAR-HNE levels increased 6.3-fold in ZK rats compared with LN animals. The treatment with L-CAR provides a further 1.7-fold increase in CAR-HNE levels compared to ZK rats, and D-CAR was slightly, but not significantly, more effective (2.2-fold increase).


The carbonyl scavenger carnosine ameliorates dyslipidaemia and renal function in Zucker obese rats.

Aldini G, Orioli M, Rossoni G, Savi F, Braidotti P, Vistoli G, Yeum KJ, Negrisoli G, Carini M - J. Cell. Mol. Med. (2010)

Selected Reaction Monitoring (SRM) chromatogram, relative to CAR-HNE parent ion → product ions transition, in LN (A), ZK (B) and Zucker treated animals (ZK + D, C; ZK + L, D) and CAR-HNE structure.
© Copyright Policy
Related In: Results  -  Collection

Show All Figures
getmorefigures.php?uid=PMC4373334&req=5

fig08: Selected Reaction Monitoring (SRM) chromatogram, relative to CAR-HNE parent ion → product ions transition, in LN (A), ZK (B) and Zucker treated animals (ZK + D, C; ZK + L, D) and CAR-HNE structure.
Mentions: By applying a recently developed LC-MS/MS method [14], we have shown that the Michael adduct between CAR and HNE is a stable and reliable biomarker of lipid peroxidation and carbonylation in vivo. By demonstrating higher levels of this adduct in urine from ZK rats compared to LN animals, we confirmed HNE overproduction in obese animals and the role of CAR as an endogenous detoxifying agent of RCS. The same analytical approach was applied in this study to confirm the in vivo RCS-trapping ability of exogenous L- and D-CAR. Figure 8 summarizes these results and shows typical LC-ESI-MS/MS profiles of urine, relative to the four groups of animals, acquired in MRM by setting the precursor ion at m/z 383.1 (CID@40.00 V). As reported in Table 2, the CAR-HNE levels increased 6.3-fold in ZK rats compared with LN animals. The treatment with L-CAR provides a further 1.7-fold increase in CAR-HNE levels compared to ZK rats, and D-CAR was slightly, but not significantly, more effective (2.2-fold increase).

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.

View Article: PubMed Central - PubMed

Affiliation: Department of Pharmaceutical Sciences Pietro Pratesi, Università degli Studi di Milano, Milan, Italy. giancarlo.aldini@unimi.it

Show MeSH
Related in: MedlinePlus