Abstract
Redox balance maintaining is a prerequisite for normal cardiomyocytes metabolism. Reperfusion injury of the heart is characterized by an explosive increase in ROS generation, cell membranes damage, dysfunction of proteins, the development of muscle contracture etc. It was shown that the hydrogen sulfide (H2S) and the precursor of its synthesis the amino acid L-cysteine provided cardioprotective effect against ischemiareperfusion, In addition, L-cysteine is one of amino acids that form an antioxidant glutathione (GSH). The aim of our work was to investigate the effect of GSH and H2S synthesis modulation on the oxidative and nitrosative stress in cardiac tissues under conditions of ischemia-reperfusion. The H2S synthesis inhibitor propargylglycine (PAG), the GSH synthesis inhibitor butionine sulfoxime (BSO) and L-cysteine were administered intraperitoneally. Next, ischemia-reperfusion of the Langendorff isolated rat heart was performed. In the tissues of rat's hearts, before and after ischemia, we determined the rate of ROS generation, content of POL products, the activity of NO synthesizing enzymes. Results of our study showed that pretreatment with PAG + L-cysteine combination prevented heart function disturbances, ROS formation, increased low molecular weight nitrosothiols content, preserved the activity of constitutive NOS and inhibited the activity of inducible NOS in the pre-ischemic period as well as in the period of reperfusion. Pretreatment with BSO in PAG + L-cysteine group significantly reduced the effectiveness of the combination and abolished cardioprotective effect. Generation of superoxide and hydroxyl anions was increased, activity of inducible NO-synthase was 3.5-fold increased comparing with PAG + L-cysteine pretreated group. Pretreatment with PAG + L-cysteine combination inhibited the formation of ROS and preserved the activity of constitutive NOS, thus providing stable production of NO. Pretreatment with BSO completely abolished an antioxidant effect of PAG + L-cysteine decreasing bioavailability of glutathione.
Highlights
Підтримання окисно-відновного балансу є необхідною умовою для забезпечення нормального метаболізму клітин серця
the use of marine objects as a source for the production of target molecules requires some optimization of existing methodological approaches to their isolation
The problem of optimization of the method of obtaining peptides from hydrobionts of the Antarctic region on the example of the hydrobiont Nacellaconcinna is solved in the work
Summary
Підтримання окисно-відновного балансу є необхідною умовою для забезпечення нормального метаболізму клітин серця. ВПЛИВ МОДУЛЮВАННЯ СИНТЕЗУ СІРКОВОДНЮ ТА ГЛУТАТІОНУ НА ОКИСНО-НІТРОЗАТИВНИЙ МЕТАБОЛІЗМ МІОКАРДА В УМОВАХ ІШЕМІЇ-РЕПЕРФУЗІЇ Метою нашої роботи було дослідити вплив модуляції синтезу GSH та H2S на окисно-нітрозативний метаболізм тканин серця в умовах ішемії-реперфузії. Премедикація BSO у групі PAG+L-цистеїн значно знижувала ефективність комбінації та погіршувала відновлення функції серця під час реперфузії.
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Schedule a callMore From: Bulletin of Taras Shevchenko National University of Kyiv. Series: Biology
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