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«Антипролиферативное действие карнозина и его производных на опухолевые клетки нейрального происхождения ...»

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ADDIN EN.CITE.DATA [20, 21, 23, 208-210]. 1.3.2. Антиоксидантные свойства карнозина и его производныхКарнозин эффективно препятствовал окислению 2,5-бис(гидроксиметил)фурана (BHMF) и N,N-диметил-4-нитрозоанилин (RNO) под действием света в растворе, содержащем фотосенсибилизатор PEVuZE5vdGU+PENpdGU+PEF1dGhvcj5EYWhsPC9BdXRob3I+PFllYXI+MTk4ODwvWWVhcj48UmVj

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ADDIN EN.CITE.DATA [211, 212]. BHMF и RNO представляют собой ловушки синглетного кислорода (1О2), ингибирование окисления ловушек с помощью карнозина указывает на способность карнозина взаимодействовать с 1О2. Кроме того, карнозин снижал интенсивность хемилюминесценции, индуцируемой синглетным кислородом, образующимся в смеси Н2О2+NaClO, подтверждая способность тушить 1О2 ADDIN EN.CITE <EndNote><Cite><Author>Швачко</Author><Year>1990</Year><RecNum>166</RecNum><DisplayText>[213]</DisplayText><record><rec-number>166</rec-number><foreign-keys><key app="EN" db-id="w2wfxafe6va9z5eev2l55aa8sxsa599eev2s">166</key></foreign-keys><ref-type name="Journal Article">17</ref-type><contributors><authors><author><style face="normal" font="default" charset="204" size="100%">Швачко,</style><style face="normal" font="default" size="100%"> </style><style face="normal" font="default" charset="204" size="100%">А.Г., Формазюк, В.Е., Сергиенко В.И.</style></author></authors></contributors><titles><title><style face="normal" font="default" charset="204" size="100%">Тушение хемилюминесценции синглетного кислорода в присутствии карнозина</style></title></titles><pages><style face="normal" font="default" charset="204" size="100%">155-156</style></pages><dates><year><style face="normal" font="default" charset="204" size="100%">1990</style></year></dates><urls></urls></record></Cite></EndNote>[213]. Интересно отметить, что при эквимолярных концентрациях эффективность тушения 1О2 карнозином была выше, чем у гистидина, известной ловушки для 1О2 PEVuZE5vdGU+PENpdGU+PEF1dGhvcj5CcmF3bjwvQXV0aG9yPjxZZWFyPjE5ODE8L1llYXI+PFJl

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ADDIN EN.CITE.DATA [211, 212, 214]. Более высокая эффективность карнозина по сравнению с гистидином, возможно, связана с особенностями внутримолекулярных взаимодействий (влияние -аланина), что приводит к большей реакционной способности гистидина в молекуле карнозина.

Методом синхронной регистрации светопоглощения при радиолизе водного раствора карнозина было выявлено образование комплекса между супероксидом и карнозином с частичным переносом заряда. Образование комплекса приводило к снижению константы скорости дисмутации О2-• и повышению его стабильности в водном растворе ADDIN EN.CITE <EndNote><Cite><Author>Pavlov</Author><Year>1990</Year><RecNum>135</RecNum><DisplayText>[14]</DisplayText><record><rec-number>135</rec-number><foreign-keys><key app="EN" db-id="w2wfxafe6va9z5eev2l55aa8sxsa599eev2s">135</key></foreign-keys><ref-type name="Journal Article">17</ref-type><contributors><authors><author>Pavlov, A. R.</author><author>Revina, A. A.</author><author>Dupin, A. M.</author><author>Boldyrev, A. A.</author><author>Iaropolov, A. I.</author></authors></contributors><titles><title>[Interactions of carnosine and superoxide radicals in aqueous solutions]</title><secondary-title>Biull Eksp Biol Med</secondary-title><alt-title>Biulleten&apos; eksperimental&apos;noi biologii i meditsiny</alt-title></titles><periodical><full-title>Biull Eksp Biol Med</full-title><abbr-1>Biulleten&apos; eksperimental&apos;noi biologii i meditsiny</abbr-1></periodical><alt-periodical><full-title>Biull Eksp Biol Med</full-title><abbr-1>Biulleten&apos; eksperimental&apos;noi biologii i meditsiny</abbr-1></alt-periodical><pages>391-3</pages><volume>110</volume><number>10</number><edition>1990/10/01</edition><keywords><keyword>Carnosine/ chemistry</keyword><keyword>Free Radicals</keyword><keyword>Hydrogen-Ion Concentration</keyword><keyword>Solutions</keyword><keyword>Superoxides/ chemistry</keyword></keywords><dates><year>1990</year><pub-dates><date>Oct</date></pub-dates></dates><orig-pub>Vzaimodeistvie karnozina s superoksidnymi radikalami v vodnykh rastvorov.</orig-pub><isbn>0365-9615 (Print)&#xD;0365-9615 (Linking)</isbn><accession-num>2177670</accession-num><urls></urls><remote-database-provider>NLM</remote-database-provider><language>rus</language></record></Cite></EndNote>[14]. Способность карнозина взаимодействовать с супероксид анионом была подтверждена в независимой работе Klebanov et al, где карнозин препятствовал восстановлению нитро-голубого тетразолия под действием О2-• образованного в смеси ксантин+ксантиноксидаза ADDIN EN.CITE <EndNote><Cite><Author>Klebanov</Author><Year>1997</Year><RecNum>144</RecNum><DisplayText>[17]</DisplayText><record><rec-number>144</rec-number><foreign-keys><key app="EN" db-id="w2wfxafe6va9z5eev2l55aa8sxsa599eev2s">144</key></foreign-keys><ref-type name="Journal Article">17</ref-type><contributors><authors><author>Klebanov, G. I.</author><author>Teselkin Yu, O.</author><author>Babenkova, I. V.</author><author>Popov, I. N.</author><author>Levin, G.</author><author>Tyulina, O. V.</author><author>Boldyrev, A. A.</author><author>Vladimirov Yu, A.</author></authors></contributors><auth-address>Russian State Medical University, Moscow, Russia.</auth-address><titles><title>Evidence for a direct interaction of superoxide anion radical with carnosine</title><secondary-title>Biochem Mol Biol Int</secondary-title><alt-title>Biochemistry and molecular biology international</alt-title></titles><periodical><full-title>Biochem Mol Biol Int</full-title><abbr-1>Biochemistry and molecular biology international</abbr-1></periodical><alt-periodical><full-title>Biochem Mol Biol Int</full-title><abbr-1>Biochemistry and molecular biology international</abbr-1></alt-periodical><pages>99-106</pages><volume>43</volume><number>1</number><edition>1997/10/07</edition><keywords><keyword>Carnosine/ metabolism/pharmacology</keyword><keyword>Luminescent Measurements</keyword><keyword>Luminol/metabolism</keyword><keyword>Nitroblue Tetrazolium/metabolism</keyword><keyword>Oxidation-Reduction</keyword><keyword>Superoxides/ metabolism</keyword><keyword>Xanthine Oxidase/metabolism</keyword></keywords><dates><year>1997</year><pub-dates><date>Sep</date></pub-dates></dates><isbn>1039-9712 (Print)&#xD;1039-9712 (Linking)</isbn><accession-num>9315287</accession-num><urls></urls><remote-database-provider>NLM</remote-database-provider><language>eng</language></record></Cite></EndNote>[17]. Сравнение эффективности тушения О2-•, образующегося в смеси глутатион+пероксидаза+люминол, выявило, что карнозин и гистидин демонстрировали примерно одинаковую эффективность, в то время как -аланин был неактивен, что указывает на определяющую роль гистидина при взаимодействии карнозина с супероксидом PEVuZE5vdGU+PENpdGU+PEF1dGhvcj5LbGViYW5vdjwvQXV0aG9yPjxZZWFyPjE5OTg8L1llYXI+

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ADDIN EN.CITE.DATA [215].

С помощью метода электронного парамагнитного резонанса (ЭПР) было продемонстрировано, что добавление карнозина к смеси реакции Фентона приводит к формированию продукта способного конкурировать со спиновой ловушкой для OH• - 5,5-диметилпирролин-N-оксидом (DMPO) ADDIN EN.CITE <EndNote><Cite><Author>Chan</Author><Year>1994</Year><RecNum>145</RecNum><DisplayText>[16, 216]</DisplayText><record><rec-number>145</rec-number><foreign-keys><key app="EN" db-id="w2wfxafe6va9z5eev2l55aa8sxsa599eev2s">145</key></foreign-keys><ref-type name="Journal Article">17</ref-type><contributors><authors><author>Chan, W. K. M., </author><author>Decker, E. A., </author><author>Lee, J. B., </author><author>Butterfield, D. A. </author></authors></contributors><titles><title>EPR spin-trapping studies of the hydroxyl radical scavenging activity of carnosine and related dipeptides</title><secondary-title>J Agric Food Chem</secondary-title></titles><periodical><full-title>J Agric Food Chem</full-title><abbr-1>Journal of agricultural and food chemistry</abbr-1></periodical><pages>1407-1410</pages><volume>42</volume><dates><year>1994</year></dates><urls></urls></record></Cite><Cite><Author>RUBTSOV</Author><Year>1991</Year><RecNum>171</RecNum><record><rec-number>171</rec-number><foreign-keys><key app="EN" db-id="w2wfxafe6va9z5eev2l55aa8sxsa599eev2s">171</key></foreign-keys><ref-type name="Journal Article">17</ref-type><contributors><authors><author>RUBTSOV, AM</author><author>SCHARA, M.</author><author>SENTJURC, M.</author><author>BOLDYREV, AA</author></authors></contributors><titles><title>HYDROXYL RADICAL-SCAVENGING ACTIVITY OF CARNOSINE - A SPIN TRAPPING STUDY</title><secondary-title>Acta Pharmaceutica Jugoslavika</secondary-title></titles><periodical><full-title>Acta Pharmaceutica Jugoslavika</full-title></periodical><pages>401-407</pages><volume>41</volume><number>4</number><dates><year>1991</year></dates><label>boldyrev1991hydroxyl1978455</label><work-type>journal article</work-type><urls><related-urls><url>http://istina.msu.ru/publications/article/1978455/</url></related-urls></urls></record></Cite></EndNote>[16, 216]. Гистидин и гомокарнозин взаимодействовали с OH• менее эффективно, чем карнозин. Образование комплексов OH• с -аланином и ГАМК обнаружено не было. Интересно отметить, что эффективность связывания OH• в смеси -аланин+гистидин была ниже, чем в присутствии карнозина, что еще раз подтверждает важную роль внутримолекулярных взаимодействий для антиоксидантного эффекта карнозина ADDIN EN.CITE <EndNote><Cite><Author>Chan</Author><Year>1994</Year><RecNum>145</RecNum><DisplayText>[16]</DisplayText><record><rec-number>145</rec-number><foreign-keys><key app="EN" db-id="w2wfxafe6va9z5eev2l55aa8sxsa599eev2s">145</key></foreign-keys><ref-type name="Journal Article">17</ref-type><contributors><authors><author>Chan, W. K. M., </author><author>Decker, E. A., </author><author>Lee, J. B., </author><author>Butterfield, D. A. </author></authors></contributors><titles><title>EPR spin-trapping studies of the hydroxyl radical scavenging activity of carnosine and related dipeptides</title><secondary-title>J Agric Food Chem</secondary-title></titles><periodical><full-title>J Agric Food Chem</full-title><abbr-1>Journal of agricultural and food chemistry</abbr-1></periodical><pages>1407-1410</pages><volume>42</volume><dates><year>1994</year></dates><urls></urls></record></Cite></EndNote>[16].

В ряде работ были продемонстрированы способности карнозина взаимодействовать с продуктами ПОЛ, препятствуя распространению окислительного повреждения. Карнозин сдерживал накопление малонового альдегида, образующегося в результате окисления фрагментов саркоплазматического ретикулума, и способствовал сохранению функций мембран ADDIN EN.CITE <EndNote><Cite><Author>Dupin</Author><Year>1984</Year><RecNum>113</RecNum><DisplayText>[18]</DisplayText><record><rec-number>113</rec-number><foreign-keys><key app="EN" db-id="w2wfxafe6va9z5eev2l55aa8sxsa599eev2s">113</key></foreign-keys><ref-type name="Journal Article">17</ref-type><contributors><authors><author>Dupin, A. M.</author><author>Boldyrev, A. A.</author><author>Arkhipenko Iu, V.</author><author>Kagan, V. E.</author></authors></contributors><titles><title>[Carnosine protection of Ca2+ transport against damage induced by lipid peroxidation]</title><secondary-title>Biull Eksp Biol Med</secondary-title><alt-title>Biulleten&apos; eksperimental&apos;noi biologii i meditsiny</alt-title></titles><periodical><full-title>Biull Eksp Biol Med</full-title><abbr-1>Biulleten&apos; eksperimental&apos;noi biologii i meditsiny</abbr-1></periodical><alt-periodical><full-title>Biull Eksp Biol Med</full-title><abbr-1>Biulleten&apos; eksperimental&apos;noi biologii i meditsiny</abbr-1></alt-periodical><pages>186-8</pages><volume>98</volume><number>8</number><edition>1984/08/01</edition><keywords><keyword>Animals</keyword><keyword>Biological Transport/drug effects</keyword><keyword>Calcium/ metabolism</keyword><keyword>Carnosine/ pharmacology</keyword><keyword>Dipeptides/ pharmacology</keyword><keyword>Lipid Peroxides/ metabolism</keyword><keyword>Muscles/drug effects/metabolism</keyword><keyword>Oxidation-Reduction/drug effects</keyword><keyword>Rana temporaria</keyword><keyword>Sarcoplasmic Reticulum/drug effects/metabolism</keyword></keywords><dates><year>1984</year><pub-dates><date>Aug</date></pub-dates></dates><orig-pub>Zashchita karnozinom transporta Ca2+ ot povrezhdenii, vyzyvaemykh perekisnym okisleniem lipidov.</orig-pub><isbn>0365-9615 (Print)&#xD;0365-9615 (Linking)</isbn><accession-num>6331862</accession-num><urls></urls><remote-database-provider>NLM</remote-database-provider><language>rus</language></record></Cite></EndNote>[18]. Карнозин также снижал количество пероксильных радикалов, образующихся в липосомах печени в результате инициации ПОЛ с помощью азосоединений PEVuZE5vdGU+PENpdGU+PEF1dGhvcj5Lb2hlbjwvQXV0aG9yPjxZZWFyPjE5ODg8L1llYXI+PFJl

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