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[The anti-ischemic and antioxidant activity of the pharmacological agonist of galanin receptor GalR2 and carnosine in in vitro and in vivo model systems]


. 2022 Jun;68(3):190-200.


doi: 10.18097/PBMC20226803190.

[Article in

Russian]

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[Article in

Russian]

L I Serebryakova et al.


Biomed Khim.


2022 Jun.

Antioxidant and anti-ischemic properties of the pharmacological agonist of galanin receptor GalR2 WTLNSAGYLLGPβAH (Gal) and its C-terminal fragment, dipeptide carnosine (βAH), were studied in the model of regional ischemia and reperfusion of the rat heart in vivo in the dose range of 0.5-5.0 mg/kg and Cu²⁺-induced free radical oxidation of low density lipoproteins (LDL) of human plasma in vitro for peptide concentrations of 0.01 mM and 0.1 mM. Gal was obtained by automatic solid phase synthesis using the Fmoc methodology; its structure was characterized by 1H-NMR spectroscopy and MALDI-TOF mass spectrometry. Intravenous administration of the optimal dose of Gal (1 mg/kg) to rats after ischemia was more effective than carnosine in reducing of the myocardial infarct size and the activity of creatine kinase-MB and lactate dehydrogenase in blood plasma at the end of reperfusion. It also improved the metabolic state of the reperfused myocardium and reduced the formation of peroxidation products during reperfusion. Gal reduced more effectively the formation of adducts of hydroxyl radicals in the interstitium of the area at risk (AAR) of the rat heart than carnosine. Carnosine at a dose of 1 mg/kg more effectively increased the activity of catalase and glutathione peroxidase in the AAR by the end of reperfusion compared to Gal. In a model of Cu²⁺-initiated oxidation of human plasma LDL 0.1 mM carnosine demonstrated a significantly more pronounced reduction in the formation of lipid radicals compared to Gal. The results show that Gal can be considered as a promising agent that reduces myocardial injury during reperfusion and oxidative stress.

Antioksidantnye i protivoishemicheskie svoĭstva farmakologicheskogo agonista retseptorov galanina WTLNSAGYLLGPβAH (Gal) i ego S-kontsevogo fragmenta dipeptida karnozina (βAH) izucheny na modeli regional’noĭ ishemii i reperfuzii serdtsa krysy in vivo v diapazone doz 0,5-5,0 mg/kg i Cu²⁺-indutsirovannogo svobodnoradikal’nogo okisleniia lipoproteinov nizkoĭ plotnosti (LNP) plazmy cheloveka in vitro dlia kontsentratsiĭ peptidov 0,01 mM i 0,1 mM. Gal poluchen avtomaticheskim tverdofaznym sintezom s ispol’zovaniem Fmoc-metodologii; ego struktura okharakterizovana s pomoshch’iu 1N-IaMR-spektroskopii i MALDI-TOF mass-spektrometrii. Vnutrivennoe vvedenie krysam optimal’noĭ dozy Gal (1mg/kg) posle ishemii v bol’sheĭ stepeni, chem v sluchae karnozina, umen’shalo razmery infarkta miokarda i snizhalo aktivnost’ kreatinkinazy-MV i laktatdegidrogenazy v plazme krovi v kontse reperfuzii, uluchshalo metabolicheskoe sostoianie reperfuziruemogo miokarda i umen’shalo obrazovanie produktov perekisnogo okisleniia pri reperfuzii. Gal umen’shal obrazovanie adduktov gidroksil’nykh radikalov v interstitsii zony riska (ZR) v dostoverno bol’sheĭ stepeni, chem karnozin. Karnozin v doze 1 mg/kg bolee éffektivno uvelichival aktivnost’ katalazy i glutationperoksidazy v ZR levogo zheludochka serdtsa krysy k kontsu reperfuzii po sravneniiu s Gal. V modeli Cu²⁺-initsiirovannogo okisleniia LNP plazmy krovi cheloveka 0,1 mM karnozin prodemonstriroval dostoverno bolee vyrazhennoe umen’shenie obrazovaniia lipidnykh radikalov po sravneniiu s Gal. Rezul’taty pokazyvaiut, chto Gal mozhno rassmatrivat’ v kachestve perspektivnogo sredstva, snizhaiushchego povrezhdeniia serdtsa pri reperfuzii i okislitel’nom stresse.


Keywords:

antioxidant enzymes; cardiac energy state; cardiac ischemia and reperfusion; carnosine; galanin; lipid peroxidation; myocardial infarction; rat.



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