Carnosine is a neuroprotective dipeptide consisting of beta-alanine and L-histidine. It demonstrates a number of useful features, including stimulation of brain and muscle microcirculation and a rejuvenating effect on cultured cells. Its activity is based on its antioxidant and antiglycating action that, in addition to heavy metal chelation and pH-buffering ability, makes carnosine an essential factor for preventing neurodegeneration and accumulation of senile features. Recently, carnosine was successfully used to treat patients after brain stroke or patients with Parkinson disease. We conclude that carnosine can be recommended for patients under oxidative stress as a natural remedy having high efficiency and no side effects.

Carnosine, a specific constituent of excitable tissues of vertebrates, exhibits a significant antioxidant protecting effect on the brain damaged by ischemic-reperfusion injury when it was administered to the animals before ischemic episode. In this study, the therapeutic effect of carnosine was estimated on animals when this drug was administered intraperitoneally (100 mg/kg body weight) after ischemic episode induced by experimental global brain ischemia. Treatment of the animals with carnosine after ischemic episode under long-term (7-14 days) reperfusion demonstrated its pronounced protective effect on neurological symptoms and animal mortality. Carnosine also prevented higher lipid peroxidation of brain membrane structures and increased a resistance of neuronal membranes to the in vitro induced oxidation. Measurements of malonyl dialdehyde (MDA) in brain homogenates showed its increase in the after brain stroke animals and decreased MDA level in the after brain stroke animals treated with carnosine. We concluded that carnosine compensates deficit in antioxidant defense system of brain damaged by ischemic injury. The data presented demonstrate that carnosine is effective in protecting the brain in the post-ischemic period.

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Purpose The aim of this study was to create and assess biological activity of a new compound based on carnosine and acetylsalicylic acid (ASA) that will comprise antioxidant effect with antiplatelet activity, while simultaneously preventing side effects on the gastrointestinal tract. Methods Salicyl-carnosine (SC) was synthesized by condensation of ASA and carnosine. Antioxidant activity was determined by spectrophotometric and chemiluminescence methods. Antiplatelet activity was carried out by the light transmissionaggregometry method using the inductor ADP. Chronic gastric ulcer in rats was modeled using glacial acetic acid. Results Using SOD-like activity, iron-induced chemiluminescence, BaSO4-activated respiratory burst, and evaluation of red blood cell structure stabilization during oxidative damage induced by sodium hypochlorite, it was shown that SC possesses antioxidant activity analogous, or better, than that of carnosine. Antiplatelet activity of SC was evaluated in the blood of healthy individuals, and was also shown to be comparable to, or exceeding that of ASA. Also SC demonstrates high resistance to hydrolysis by tissue and serum carnosinases. Most importantly, it was shown that SC has protected the gastric mucosa against the formation of stomach ulcerative lesions and promoted their epithelization, therefore overcoming the undesirable inherent side effects of ASA. Conclusions SC preserves pharmacologically significant properties of ASA and carnosine while retaining an anti-ulcer activity and resistance to the carnosinase hydrolysis at the same time. These properties are particularly promising for the potential development of new anti-inflammatory and antithrombotic drugs. KeywordsCarnosine . Acetylsalicylic acid . Salicylic acid . Antioxidant . Antiplatelet action . Gastrointestinal ulcer Abbreviations ASA acetylsalicylic acid CL chemiluminescence COX cyclooxygenase HPLC high performance liquid chromatography HRMS high resolution mass spectrometry LP lipoproteins LPO lipid peroxidation NBT nitroblue tetrazolium NSAIDs non-steroidal anti-inflammatory drugs

Two novel derivatives of carnosine--(S)-trolox-L-carnosine (STC) and (R)-trolox-L-carnosine (RTC) are characterized in terms of their antioxidant and membrane-stabilizing activities as well as their resistance to serum carnosinase. STC and RTC were synthesized by N-acylation of L-carnosine with (S)- and (R)-trolox, respectively. STC and RTC were found to react more efficiently with 2,2-diphenyl-1-picrylhydrazyl radical (DPPH) and protect serum lipoproteins from Fe(2+)-induced oxidation more successfully than carnosine and trolox. At the same time, STC, RTC and trolox suppressed oxidative hemolysis of red blood cells (RBC) less efficiently than carnosine taken in the same concentration. When oxidative stress was induced in suspension of cerebellum granule cells by their incubation with N-methyl-D-aspartate (NMDA), or hydrogen peroxide (H(2)O(2)), both STC and RTC more efficiently decreased accumulation of reactive oxygen species (ROS) than carnosine and trolox. Both STC and RTC were resistant toward hydrolytic degradation by human serum carnosinase. STC and RTC were concluded to demonstrate higher antioxidant capacity and better ability to prevent cerebellar neurons from ROS accumulation than their precursors, carnosine and trolox.

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