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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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Glomerular capillary loops in LN (A), ZK (B) and Zucker treated animals (ZK + L, C; ZK + D, D). Arrows point to GBM. Up left: LN rat with normal GBM thickness, podocyte and foot processes; up right: ZK rat with thick GBM, edematous podocyte and foot processes; down left and down right: ZK + L and ZK + D rats with almost normal GBM thickness, podocyte and foot processes. GBM: glomerular basement membrane; P: podocyte, FP: foot processes.
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fig07: Glomerular capillary loops in LN (A), ZK (B) and Zucker treated animals (ZK + L, C; ZK + D, D). Arrows point to GBM. Up left: LN rat with normal GBM thickness, podocyte and foot processes; up right: ZK rat with thick GBM, edematous podocyte and foot processes; down left and down right: ZK + L and ZK + D rats with almost normal GBM thickness, podocyte and foot processes. GBM: glomerular basement membrane; P: podocyte, FP: foot processes.

Mentions: At the ultrastructural level, the increase in GBM thickness in ZK rats compared to LN animals (5.8 ± 0.6 nm versus 3.9 ± 0.5 nm; P < 0.01) is another important morphologic modification in renal disease linked to metabolic syndrome, already reported in Zucker obese rats [52] and in FVBdb/db diabetic mice [51]. Although measurements were done on only four animals for each group, the results reported in Figure 6D clearly indicate the ability of both the treatments to prevent GBM alteration, with D-CAR being able to maintain the GBM thickness in the range of the LN controls (3.75 ± 0.8 nm). Furthermore, in treated rats, glomeruli foot processes of podocytes show normal appearance whereas in ZK they are swollen, as clearly shown in Figure 7A–D.


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)

Glomerular capillary loops in LN (A), ZK (B) and Zucker treated animals (ZK + L, C; ZK + D, D). Arrows point to GBM. Up left: LN rat with normal GBM thickness, podocyte and foot processes; up right: ZK rat with thick GBM, edematous podocyte and foot processes; down left and down right: ZK + L and ZK + D rats with almost normal GBM thickness, podocyte and foot processes. GBM: glomerular basement membrane; P: podocyte, FP: foot processes.
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Related In: Results  -  Collection

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

fig07: Glomerular capillary loops in LN (A), ZK (B) and Zucker treated animals (ZK + L, C; ZK + D, D). Arrows point to GBM. Up left: LN rat with normal GBM thickness, podocyte and foot processes; up right: ZK rat with thick GBM, edematous podocyte and foot processes; down left and down right: ZK + L and ZK + D rats with almost normal GBM thickness, podocyte and foot processes. GBM: glomerular basement membrane; P: podocyte, FP: foot processes.
Mentions: At the ultrastructural level, the increase in GBM thickness in ZK rats compared to LN animals (5.8 ± 0.6 nm versus 3.9 ± 0.5 nm; P < 0.01) is another important morphologic modification in renal disease linked to metabolic syndrome, already reported in Zucker obese rats [52] and in FVBdb/db diabetic mice [51]. Although measurements were done on only four animals for each group, the results reported in Figure 6D clearly indicate the ability of both the treatments to prevent GBM alteration, with D-CAR being able to maintain the GBM thickness in the range of the LN controls (3.75 ± 0.8 nm). Furthermore, in treated rats, glomeruli foot processes of podocytes show normal appearance whereas in ZK they are swollen, as clearly shown in Figure 7A–D.

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