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: A 2.4-fold increase in plasma creatinine concentration was observed in ZK compared to LN rats (P < 0.001), an effect that was significantly restrained by both L-CAR (–31.7%versus ZK; P < 0.001) and D-CAR (–36%versus ZK; P < 0.001) (data not shown). A similar protective trend was also observed by considering the urinary albumin, creatinine and protein excretions, which were increased 14-fold (P < 0.001), 2.5-fold (P < 0.001) and 6.8-fold (P < 0.001), respectively, in ZK rats compared to the LN animals. Both L-CAR and D-CAR provided a significant protection against the development of proteinuria/albuminuria/creatininuria, which was restrained by approximately 50% (data not shown). The overall renoprotective effect of both the compounds is well described by the parameters reported in Figure 6. Creatinine clearance (expressed as GFR), was reduced by 45.8% in ZK compared to LN rats, and was significantly improved by both L-CAR (+28.3%versus ZK) and D-CAR (+25.1%versus ZK) (Fig. 6A). A more pronounced protective effect was induced by both the compounds on the urinary albumin-to-creatinine ratio, which is the early, easily measurable and reliable biomarker of nephropathy  (Fig. 6C). The 35-fold increase observed in ZK compared to LN animals was, in fact, restrained by 65–70% in both L- and D-CAR treated animals.
Affiliation: Department of Pharmaceutical Sciences Pietro Pratesi, Università degli Studi di Milano, Milan, Italy. email@example.com