l-carnosine (β-alanyl-l-histidine) and carcinine (β-alanylhistamine) act as natural antioxidants with hydroxyl-radical-scavenging and lipid-peroxidase activities

Abstract

Carnosine (beta-alanyl-L-histidine) and carcinine (beta-alanylhistamine) are natural imidazole-containing compounds found in the non-protein fraction of mammalian tissues. Carcinine was synthesized by an original procedure and characterized. Both carnosine and carcinine (10-25 mM) are capable of inhibiting the catalysis of linoleic acid and phosphatidylcholine liposomal peroxidation (LPO) by the O2(-.)-dependent iron-ascorbate and lipid-peroxyl-radical-generating linoleic acid 13-monohydroperoxide (LOOH)-activated haemoglobin systems, as measured by thiobarbituric-acid-reactive substance. Carcinine and carnosine are good scavengers of OH. radicals, as detected by iron-dependent radical damage to the sugar deoxyribose. This suggests that carnosine and carcinine are able to scavenge free radicals or donate hydrogen ions. The iodometric, conjugated diene and t.l.c. assessments of lipid hydroperoxides (13-monohydroperoxide linoleic acid and phosphatidylcholine hydroperoxide) showed their efficient reduction and deactivation by carnosine and carcinine (10-25 mM) in the liberated and bound-to-artificial-bilayer states. This suggests that the peroxidase activity exceeded that susceptible to direct reduction with glutathione peroxidase. Imidazole, solutions of beta-alanine, or their mixtures with peptide moieties did not show antioxidant potential. Free L-histidine and especially histamine stimulated iron (II) salt-dependent LPO. Due to the combination of weak metal chelating (abolished by EDTA), OH. and lipid peroxyl radicals scavenging, reducing activities to liberated fatty acid and phospholipid hydroperoxides, carnosine and carcinine appear to be physiological antioxidants able to efficiently protect the lipid phase of biological membranes and aqueous environments.

Zinc deficiency or excess within the physiological range increases genome instability and cytotoxicity, respectively, in human oral keratinocyte cells

“…Carnosine is an antioxidant, derived from the amino acids b-histidine and L-alanine, and has been shown to protect against X-ray irradiation and promote wound healing (Klebanov et al 1998;Hipkiss 1998;Hipkiss and Chana 1998;Hipkiss et al 1997;). Several potential antioxidant mechanisms which maybe involved include: (a) its chelating action against metal ions; (b) superoxide-dismutase (SOD)-like activity; and (c) ROS and free radical scavenging (Babizhayev et al 1994;. Similarly, it is possible that some observed effects of ZnSO 4 may have been influenced not only by Zn but also by the SO 4 2-ion.…”

Carnosine and cancer: a perspective

“…In general, ionizing radiation is still a highly effective therapeutic tool for different types of cancer and is, therefore, frequently employed. Since formation of ROS is one of the major reasons for cellular injury after radiation (Riley 1994), carnosine may protect healthy tissue from damage and inflammation due to its antioxidant (Babizhayev et al 1994;Chan et al 1994) or anti-inflammatory properties [for a review see (Nagai 1980)]. The hypothesis of Guney et al (2006) has not been tested in humans, but 20 years ago Severin et al (1990) reported that carnosine administered per os (50-200 mg/kg/day) during a period of 20 days prior to irradiation increased survival rates in albino mice subjected to whole-body X-irradiation (5.0 Gy).…”

Immunostimulating activities of the novel peptidomimetic L-glutamyl-histamine

“…Chemically, the antioxidant activity of L-Glu-Hist shown at high concentrations of peptidomimetic is not due solely to the imidazole moieties of the molecule, as imidazole itself did not show antioxidant activity, and histamine exhibited a pro-oxidant action dependent on the concentration of catalytically active free iron ions (this study and [17]). The antioxidant activity of L-Glu-Hist may involve the reduction of oxidative potential or stabilization of the imidazole radical, due probably to the peptide bond.…”

“…The other tested compounds, i.e. imidazole and b-alanine, were inactive to LPO (see [17]), suggesting that the redox potential of the whole peptidomimetic molecule is essential for exhibition of its pro-or antioxidant activities.…”

“…Recently the original family of histamine-containing peptidomimetic compounds has been synthesized [16,17]. Its first-representative natural pseudodipeptide carcinine ( balanylhistamine) has been described as a universal antioxidant in both lipid and aqueous domains with repairing activity to cell membrane damage linked physiologically to Lcarnosine ( b -alanyl-L-histidine) in the carnosine-histidinehistamine metabolic pathway and endowed with higher resistance to enzymatic hydrolysis comparatively to L-carnosine.…”