Inhibition of low-density lipoprotein oxidation by carnosine and histidine

Carnosine is a beta -alanylhistidine dipeptide found in skeletal muscle and nervous tissue that has been reported to possess antioxidant activity. Car nosine is a potential dietary antioxidant because it is absorbed into plasm a intact. This research investigated the ability of carnosine to inhibit th e oxidation of low-density lipoprotein (LDL) in comparison to its constitue nt amino acid, histidine. Carnosine (3 muM) inhibited Cu2+-promoted LDL (20 mug of protein/mL) oxidation at carnosine/copper ratios as low as 1:1, as determined by lass of tryptophan fluorescence and formation of conjugated d ienes. Carnosine (6 muM) lost its ability to inhibit conjugated diene forma tion and tryptophan oxidation after 2 and 4 h of incubation, respectively, of LDL with 3 muM CU2+. Compared to controls, histidine (3 muM) inhibited t ryptophan oxidation and conjugated diene formation 36 and 58%, respectively , compared to 21 and 0% for carnosine (3 CIM) after 3 h of oxidation. Histi dine was more effective at inhibiting copper-promoted formation of carbonyl s on bovine serum albumin than carnosine, but carnosine was more effective at inhibiting copper-induced ascorbic acid oxidation than histidine. Neithe r carnosine nor histidine was a strong inhibitor of 2,2'-azobis(2-amidinopr opane) dihydrochloride-promoted oxidation of LDL, indicating that their mai n antioxidant mechanism is through copper chelation.