Antioxidant activity of carnosine, homocarnosine, and anserine present in muscle and brain.

Abstract

Carnosine, homocarnosine, and anserine are present in high concentrations in the muscle and brain of many animals and humans. However, their exact function is not clear. The antioxidant activity of these compounds has been examined by testing their peroxyl radical-trapping ability at physiological concentrations. Carnosine, homocarnosine, anserine, and other histidine derivatives all showed antioxidant activity. All of these compounds showing peroxyl radicaltrapping activity were also electrochemically active as reducing agents in cyclic voltammetric measurements. Furthermore, carnosine inhibited the oxidative hydroxylation of deoxyguanosine induced by ascorbic acid and copper ions. Other roles of carnosine, such as chelation of metal ions, quenching of singlet oxygen, and binding of hydroperoxides, are also discussed. The data suggest a role for these histidine-related compounds as endogenous antioxidants in brain and muscle.One of the processes involved in the adaptation of organisms to live in an aerobic atmosphere was the development of mechanisms for defense against damage induced by oxygen and active oxygen species (1). Active oxygen has been suggested as a major cause of cancer, aging, and several diseases (1-6). These reactive compounds can react with DNA, RNA, lipids, and proteins (1-7).Natural defense mechanisms vary from one species to another and within the tissues of the same species. Skeletal muscle and brain are two of the tissues that have the most active oxidative metabolism, yet the concentrations of the antioxidants vitamin E and vitamin C in these tissues are not particularly high (8,9). Carnosine (,B-alanyl-L-histidine) was discovered at the beginning of the century in skeletal muscle (10). Since then, carnosine and related compounds anserine (8-alanyl-3-methyl-L-histidine) and homocarnosine (y-aminobutyryl-Lhistidine) have been reported (11) to be present in the range of 1-20 mM in the skeletal muscles of many vertebrates. There are high levels of carnosine in human muscles (2-20 mM) (11), olfactory epithelium and bulbs (0.3 mM-5 mM) (12)(13)(14)(15), and in other parts of the brain. Homocarnosine is present in cerebrospinal fluid and brain (2-50 p.M) (12)(13)(14)(15)(16)(17), and anserine is present in the brain (18).Although it is accepted that camosine and its analogues should play some physiological role in muscle and brain, no unified hypothesis exists that can satisfactorily explain their role (18). Carnosine has been postulated to act as a buffer to neutralize lactic acid produced in skeletal muscle that is undergoing anaerobic glycolysis (19 Assay for the Lipid Peroxyl Radical-Trapping Activity. The azo compounds 2,2'-azobis(2,4-dimethylvoleronitrile) (AMVN) and 2,2'-azobis(2-amidinopropane dihydrochloride) (AAPH) (Polyscience, Warrington, PA) were used as free-radical initiators in both homogeneous and liposome systems (30)(31)(32). The rate of peroxyl-radical formation from these initiators is constant at a given temperature and, once produced, can initiate free-radical ch...

Carnosine-related dipeptides in the mammalian brain

“…In our opinion, the hypothetical role(s) of carnosine-related dipeptides could be linked to some common feature(s) concerning the metabolism of these cell populations, although no direct evidence in this direction is at present available. Nevertheless, there is strong evidence that carnosine and structurally related dipeptides possess a wide range of properties, such as antioxidant, metal chelator, free radical scavenger, inhibitor of protein glycosilation (Boldyrev et al, , 1988(Boldyrev et al, , 1997Kohen et al, 1988;Boldyrev, 1993;Hipkiss et al, 1995;Preston et al, 1998; for review, see Hipkiss, 1998), which enable them to prevent several types of damage responsible for cell senescence (McFarland and Holliday, 1994;Sri-Kantha et al, 1996). Thus, carnosine-related dipeptides could exert a protective role in cell populations of the nervous system which, due to their location and/or function and metabolism, can come in contact with potentially harmful substances.…”

“…In particular, neurons contain very low levels of reduced glutathione, an antioxidant responsible for removal of cytosolic peroxides (Slivka et al, 1987), and their membranes contain a high proportion of freeradical-susceptible polyunsaturated fatty acids (see Evans, 1993). Interestingly enough, several studies demonstrated a significative antioxidant activity for carnosine-related dipeptides, both in muscle and brain tissue (see for example Boldyrev et al, 1987Boldyrev et al, , 1988Boldyrev et al, , 1997Kohen et al, 1988;Boldyrev, 1993). The activity showed by these dipeptides is due to the imidazole moiety of the molecule, and consists of several anti-oxidant properties, i.e.…”

“…The activity showed by these dipeptides is due to the imidazole moiety of the molecule, and consists of several anti-oxidant properties, i.e. stabilization of membranes (Boldyrev et al, 1988), scavenging of free radical intermediates (Kohen et al, 1988;Salim-Hanna et al, 1991;Pavlov et al, 1993), chelation of divalent transition metals such as iron, copper and zinc (Brown, 1981;Kohen et al, 1988;Klebanov et al, 1998), elimination of lipid peroxidation products in a nonenzymatic way Dupin et al, 1987). These properties are strictly related to each other; for example, important compounds in free radical biochemistry, such as hydrogen peroxide, in the presence of transition metal ions produce the more reactive and damaging hydroxyl radical (Cheeseman and Slater, 1993).…”

Oxaliplatin complexes with carnosine and its derivatives: in vitro cytotoxicity, mass spectrometric and computational studies with a focus on complex fragmentation

“…[24] The endogenous dipeptide L-carnosine (β-alanyl-L-histidine) was discovered by Gulewitsch and Amiradzibi [25] from muscle tissue extracts in 1900 [26,27] and is found in several organs including the brain (olfactory bulb and hippocampus) [28], cardiac muscle, kidney and stomach. [29,30] In the skeletal muscle and nerve cells it is found at concentrations of up to 20 mM.…”

Aminoacyl-histidine dipeptides in the glial cells of the adult rabbit forebrain☆,1

“…An involvement in neurotransmission within the olfactory system has been proposed in the past [23]. Nevertheless, the distribution of carnosine-LI in the central nervous system (CNS), prevalently associated to glial/ependymal cells [3,7,26] along with the identification of several effects displayed by these molecules in vitro [4,5,13,18,24], strongly suggest that they could subserve other functions [7]. In the mammalian brain, carnosine has been detected almost exclusively in astrocytes, oligodendrocytes, ependymal cells and tanycytes [3,10,26; for review see Ref.…”