Carnosine attenuates the development of senile features when used as a supplement to a standard diet of senescence accelerated mice (SAM). Its effect is apparent on physical and behavioral parameters and on average life span. Carnosine has a similar effect on mice of the control strain, but this is less pronounced due to the non-accelerated character of their senescence processes.

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A positive dose-dependent effect of carnosine (beta-alanyl-L-histidine) on the lifespan of male Drosophila melanogaster flies was shown. The mean lifespan of male flies receiving 200 mg/liter carnosine approached that of females. At the same time carnosine had no effect on the lifespan of female flies. This positive effect of carnosine probably reflects its protective action against age-related accumulation of free radicals and did not depend on carnosine metabolism in the body. Addition of 200 mg/liter histidine and beta-alanine (separately or in combination) had no effect on the mean lifespan of flies.

The effect of dietary carnosine on the behavioral and biochemical characteristics of rats under experimental ischemia was studied. Carnosine was shown to improve the animals orientation and learning in "Open Field" and "T-Maze" tests, and this effect was accompanied with an increase in glutamate binding to N-methyl-D-aspartate (NMDA) receptors in brain synaptosomes. Long-term brain ischemia induced by both sides' occlusion of common carotid arteries resulted in 55% mortality of experimental rats, and those who survived were characterized by partial suppression of orientation in T-maze. In the group of rats treated with carnosine, mortality after ischemic attack was decreased (from 55% to 17%) and most of the learning parameters were kept at the pre-ischemic level. Monoamine oxidase B (MAO B) activity in brain of the carnosine treated rats was not changed by ischemia significantly (compared to that of ischemic untreated rats) but NMDA binding to brain synaptosomal membranes being increased by ischemic attack was significantly suppressed and reached the level characteristic of normal brain. The suggestion was made that carnosine possesses a dual effect on NMDA receptors resulting in increase in their amount after long-term treatment but decrease the capacity to bind NMDA after ischemic attack.

Bioactive peptide carnosine ([3-alanyl-L-histidine) and its acetylated derivative added to cardioplegic solution in physiological concentrations (2-10 raM) promote complete recovery of the contractile function of rat heart after cardioplegia. Carnosine prevented the release of myoglobin, while acetylcarnosine prevented the loss of both myoglobin and nucleotides. These data attest to membrane-protective effects of these compounds. Key Words: carnosine; acetylcarnosine; cardiac ischemia; cardioplegyAt present, cardiac arrest with cardioplegic solutions containing high concentrations of K § and/or Mg > is widely used in cardiac surgery. However, cardiac contractility is often impaired during reperfusion period because of inadequacy of the anti-ischemic protection [8]. More than 50 different compositions of cardioplegic solutions have been proposed, but all of them remain far form perfect [3,4,8]. Recent attention has been focused on histidine-containing peptides, hydrophilic cell antioxidants possessing membrane-stabilizing and antioxidant properties [2]. Despite similar physicochemical properties of carnosine and acetylcarnosine (AC) their distribution in the organism is tissue specific: carnosine is predominantly localized in skeletal muscles (10-40 raM), while in the myocardium almost all carnosine is acetylated on its animo group. The total concentration of histidine-containing peptides in mammalian heart is about 10 mM [9]. The mechanism of this unequal distribution remains unclear. Both peptides exhibit a protective effect in subtotal myocardial ischemia [1]. In light of this we compared the effects of these compounds on ischemic heart using a cardioplegic solution (CPS). MATERIALS AND METHODSExperiments were carried out on Langendorf-perfused hearts from albino random-bred rats. The rats were decapitated under ether narcosis, the chest was opened, and the heart was removed and placed into cool perfusion solution containing (in raM): 140 NaCI, 0.5 NaH2PO 4, 5 KC1, 5 Trizma Base (pH 7.4), 11 glucose, and 2 CaC12. The aorta was cannulated and the heart was perfused with warm (37~ oxygenated solution at a rate of 10 ml/min/g wet tissue.In all experiments, the hearts were perfused for 15 min with the initial solution until stabilization of the contractile function and parameters of heart function at the end of this stabilization period were taken as 100%. Cardiac arrest was induced by 2-rain perfusion with CPS containing (in mM): 110 NaC1, 16 KC1, 20 NaHCO 3 (pH 7.8), 16 MgCI 2, and 1.2 CaC12 and the coronary flow was stopped for 30 rain tbr total ischemia modeling. Test agents were added to CPS in concentrations from 2 to 10 mM corresponding to their concentrations in native heart [2,9]. Reperfusion was performed with the initial solution. Temperature was maintained at 37~ throughout the experiment. In special experimental series hypothermic conditions were created. To this end CPS was cooled to 21_+2~ before perfusion. When CPS containing 10 mM AC was used, 3-rain perfusion was required for cardiac arrest (in