Antioxidative properties of histidine-containing dipeptides from skeletal muscles of vertebrates

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 the voluntary musculature, during muscle performance, the dipeptides show remarkable buffering properties by neutralizing the largescale formation of lactic acid, thus preventing the decrease of cytosolic pH (Bate-Smith, 1938;Skulachev, 1978). In addition, several histidine-containing dipeptides display antioxidant properties by preventing the accumulation of oxidized products derived from the lipid peroxidation of biological membranes (Boldyrev et al, 1988;Boldyrev, 1993;Klebanov et al, 1998; for the antioxidant effect of carnosine and other hypothetical roles in the nervous system, see section 4). Other less substantiated hypotheses have also been suggested: some consider these molecules as products of redundant metabolic pathways, which accumulate as a result of degradation of longer polypeptide chains.…”

“…These compounds can exert a nonspecific buffering function during muscle performance; however, this property seems to be restricted to muscle tissue and plays only an accessory role in the overall potent buffering effect of cytosolic proteins/components (Boldyrev et al, 1988). On the other hand, it is well known that some physiological processes such as muscle performance and electrical conduction along nerve fibers involve free radical lipid peroxidation in biological membranes, and that skeletal muscle and brain are two of the tissues which have the most active oxidative metabolism (Vladimirov and Archakov, 1972;Evans, 1993).…”

“…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).…”