دورية أكاديمية

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

التفاصيل البيبلوغرافية
العنوان: [The anti-ischemic and antioxidant activity of the pharmacological agonist of galanin receptor GalR2 and carnosine in in vitro and in vivo model systems].
عنوان ترانسليتريتد: Protivoishemicheskaia i antioksidantnaia aktivnost' farmakologicheskogo agonista retseptora galanina GalR2 i karnozina v model'nykh sistemakh in vitro i in vivo.
المؤلفون: Serebryakova LI; National Medical Research Center for Cardiology, Moscow, Russia., Studneva IM; National Medical Research Center for Cardiology, Moscow, Russia., Veselova OM; National Medical Research Center for Cardiology, Moscow, Russia., Dobrokhotov IV; National Medical Research Center for Cardiology, Moscow, Russia., Konovalova GG; National Medical Research Center for Cardiology, Moscow, Russia., Timoshin AA; National Medical Research Center for Cardiology, Moscow, Russia., Abramov AA; National Medical Research Center for Cardiology, Moscow, Russia., Avdeev DV; National Medical Research Center for Cardiology, Moscow, Russia., Sidorova MV; National Medical Research Center for Cardiology, Moscow, Russia., Lankin VZ; National Medical Research Center for Cardiology, Moscow, Russia., Pisarenko OI; National Medical Research Center for Cardiology, Moscow, Russia.
المصدر: Biomeditsinskaia khimiia [Biomed Khim] 2022 Jun; Vol. 68 (3), pp. 190-200.
نوع المنشور: Journal Article
اللغة: Russian
بيانات الدورية: Publisher: Rossiĭskai︠a︡ akademii︠a︡ medit︠s︡inskikh nauk Country of Publication: Russia (Federation) NLM ID: 101196966 Publication Model: Print Cited Medium: Print ISSN: 2310-6972 (Print) Linking ISSN: 23106905 NLM ISO Abbreviation: Biomed Khim Subsets: MEDLINE
أسماء مطبوعة: Original Publication: Moskva : Rossiĭskai︠a︡ akademii︠a︡ medit︠s︡inskikh nauk, 2003-
مواضيع طبية MeSH: Carnosine*/pharmacology , Carnosine*/therapeutic use , Myocardial Reperfusion Injury*/drug therapy , Myocardial Reperfusion Injury*/metabolism, Animals ; Antioxidants/metabolism ; Ischemia/drug therapy ; Ischemia/metabolism ; Myocardium/metabolism ; Rats ; Rats, Wistar ; Receptors, Galanin/agonists
مستخلص: 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.
فهرسة مساهمة: Keywords: antioxidant enzymes; cardiac energy state; cardiac ischemia and reperfusion; carnosine; galanin; lipid peroxidation; myocardial infarction; rat
Local Abstract: [Publisher, Russian] 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.
المشرفين على المادة: 0 (Antioxidants)
0 (Receptors, Galanin)
8HO6PVN24W (Carnosine)
تواريخ الأحداث: Date Created: 20220619 Date Completed: 20220621 Latest Revision: 20220621
رمز التحديث: 20240628
DOI: 10.18097/PBMC20226803190
PMID: 35717583
قاعدة البيانات: MEDLINE