A carnosine analog with therapeutic potentials in the treatment of disorders related to oxidative stress.

Publisher: Public Library of Science Country of Publication: United States NLM ID: 101285081 Publication Model: eCollection Cited Medium: Internet ISSN: 1932-6203 (Electronic) Linking ISSN: 19326203 NLM ISO Abbreviation: PLoS One Subsets: MEDLINE

Original Publication: San Francisco, CA : Public Library of Science

Antioxidants/*pharmacology ; Carnosine/*analogs & derivatives ; Oxidative Stress/*drug effects; Abietanes/pharmacology ; Animals ; Anserine/pharmacology ; Apoptosis/drug effects ; Carnosine/pharmacology ; Cell Line ; Cell Survival/drug effects ; Inflammation/drug therapy ; Metabolic Diseases/drug therapy ; Metabolic Diseases/metabolism ; Metabolic Diseases/pathology ; Microscopy, Electron, Scanning ; Models, Biological ; Muscle Fibers, Skeletal/drug effects ; Muscle Fibers, Skeletal/metabolism ; Muscle Fibers, Skeletal/pathology ; Peroxisome Proliferator-Activated Receptor Gamma Coactivator 1-alpha/metabolism ; Rats ; Sirtuins/metabolism ; Superoxide Dismutase/metabolism

Interactive relationships among metabolism, mitochondrial dysfunction and inflammation at skeletal muscle level play a key role in the pathogenesis of disorders related to oxidative stress. Mitochondrial dysfunction and oxidative stress result in cellular energy deficiency, inflammation and cell death inducing a vicious cycle that promotes muscle wasting. The histidine-containing dipeptides, carnosine and anserine, are carbonyl scavengers whose cytoprotective contributions extend beyond the antioxidant defence, but the physiological meaning of these capacities is actually limited. In the present study, we compared and investigated the potential protective effects of three different histidine-containing dipeptides: carnosine, anserine and carnosinol, a carnosine-mimetic new compound, against oxidative stress induction in rat L6 skeletal muscle cells. The hydrogen peroxide induced-oxidative stress significantly altered cell morphology, induced apoptosis, oxidative stress and inflammation, decreased mitochondrial peroxisome proliferator-activated receptor gamma coactivator-1α (PGC-1α)/sirtuin3 pathway and the antioxidant system. Notably, all three investigated dipeptides in the present study, with a different extent and in a concentration-dependent manner, reduced myotube oxidative stress, apoptosis and inflammation. The present study underlined that carnosinol, maintaining the safety condition of carnosine and anserine, was the more efficient studied dipeptide in the preservation of mitochondrial environment mediated by PGC-1α and sirtuin3 expression and thereby in the reduction of oxidative stress-related alterations in this in vitro skeletal muscle model. Furthermore, we observed that carnosinol's antioxidant effects are not blocked inhibiting sirtuin3, but are maintained with almost the same extend, indicating its multiple capacities of reactive carbonyl species-scavenging and of mitochondrial modulation through PGC-1α. In conclusion, carnosinol retained and surpassed the efficacy of the well-known investigated histidine-containing dipeptides improving oxidative stress, inflammation and also cell metabolism and so becoming a greatly promising therapeutic carnosine derivate.
Competing Interests: The authors have declared that no competing interests exist.

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0 (Abietanes)
0 (Antioxidants)
0 (Peroxisome Proliferator-Activated Receptor Gamma Coactivator 1-alpha)
0 (Ppargc1a protein, rat)
0 (SIRT3 protein, rat)
483O455CKD (carnosol)
8HO6PVN24W (Carnosine)
EC 1.15.1.1 (Superoxide Dismutase)
EC 1.15.1.1 (superoxide dismutase 2)
EC 3.5.1.- (Sirtuins)
HDQ4N37UGV (Anserine)

Date Created: 20190410 Date Completed: 20200115 Latest Revision: 20200827

20250114

PMC6456212

10.1371/journal.pone.0215170

30964920