The purpose of this study is to investigate the effects of bioflavonoids, epigallocatechin-3-gallate (EGCG) and quercetin, on the production of reactive oxygen and nitrogen species in the liver of rats under round-the-clock light exposure with an intensity of 1500 lux for 30 days while being kept on carbohydrate-lipid diet (20% fructose solution and appropriate food) for 60 days. In the liver tissues, the rate of the superoxide anion production by NADPH-dependent electron transport chains (microsomal monooxygenases and constitutive uncoupled NO synthases) increased by 1.93 times, by the mitochondrial respiratory chain by 1.89 times, and it was doubled by leukocyte NADPH-oxidase. The total activity of NO synthase was increased by 2.35 times, the activity of its inducible isoform increased by 2.57 times, and the concentration of alkali and alkaline earth metals peroxynitrites elevated by 1.68 times. Administration of bioflavonoids-epigallocatechin-3-gallate and quercetinsignificantly restrained the rate of superoxide anion production in the liver tissues by microsomal monooxygenases and NO synthase by 39.1 and 40.1%, by the mitochondrial respiratory chain by 37.2 and 34.4%, by leukocyte NADPH-oxidase by 35.0 and 32.1%, respectively. Epigallocatechin-3-gallate and quercetin inhibited the total activity of NO-synthase by 46.7 and 36.2%, the activity of its inducible isoform by 49.6 and 39,0%, increased the activity of the constitutive isoenzyme NO-synthase by 2.9 times and its coupling index by 4.5 and 4.7 times. Additionally, administration of these bioflavonoids lowered the concentration of peroxynitrites of alkali and alkaline earth metals by 30.5 and 34.3% compared to the respective values obtained in the group of rats, which did not receive the bioflavonoids, but were exposed to light and carbohydrate-lipid-rich diet. We suggest that epigallocatechin3-gallate and quercetin in the above experimental conditions are effective means to restrain the formation of reactive oxygen and nitrogen species in the liver tissue.
Досліджували вплив гіпомелатонінемії, індукованої цілодобовим освітленням щурів інтенсивністю 1500 лк протягом 60 діб, на вуглеводний і ліпідний обмін за умов призначення висококалорійної вуглеводно-ліпідної дієти (20 %-й розчин фруктози та відповідний раціон). Виявлено, що за цих умов зменшувалася концентрація мелатоніну у сироватці крові на 55,6 % порівняно з результатом, отриманим при окремому цілодобовому освітленні. У тварин спостерігалися більш глибокі метаболічні порушення, притаманні синдрому інсулінорезистентності (рівень гіперінсулінемії, дисліпопротеїнемії, гіпо-α-ліпопротеїнемії, гіпертригліцеридемії, підвищення маси вісцерального жиру). Це супроводжувалося розвитком декомпенсованого пероксидного окиснення ліпідів у крові щурів, зменшенням антиоксидантного потенціалу, але без істотних змін вмісту маркерів системного запалення (фактора некрозу пухлини α та церулоплазміну). При цьому утворення вторинних продуктів пероксидації (сполук, що реагують з тіобарбітуровою кислотою) перевищувало на 49,1 та 11,9 % відповідний результат груп з окремим впливом цілодобового освітлення та дієти. Ключові слова: синдром інсулінорезистентності; гіпомелатонінемія; висококалорійна вуглеводноліпідна дієта; вуглеводний і ліпідний обмін; системна запальна відповідь.
This article describes the effect of NF-κB inhibitor ammonium pyrrolidine dithiocarbamate and Nrf2 inducer dimethylfumarate on indicators of oxidative-nitrosative stress in skeletal muscles of rats with chronic hypomelatoninemia, induced by roundthe-clock illumination with an intensity of 1500 lux for 30 days, against the background of a carbohydrate-lipid diet (20% fructose solution and appropriate food) for 60 days. The study demonstrated that the administration of ammonium pyrrolidine dithiocarbamate and dimethylfumarate under the experimental conditions impedes the development of hypomelatoninemia, this was accompanied by a two-fold increase in the blood serum melatonin concentration compared to the control group. Moreover, the administration of ammonium pyrrolidine dithiocarbamate and dimethylfumarate significantly reduces the production of superoxide anion radical by electron transport chains of mitochondria (by 47.9 and 51.3%) and sarcoplasmic reticulum (by 48.6 and 52.0%) in the homogenate of femoral muscles, the total activity of NO synthase (by 37.2 and 36.2%) and its inducible isoform (by 41.1 and 40.0%), the concentration of peroxynitrites of alkaline and alkaline earth metals (by 37.2 and 41.0 %), while the activity of constitutive NO-synthases (by 2.9 and 2.8 times) and their conjugation index (by 5.2 and 5.4 times) increases compared to the respective control values. We suggest that modulators of redox-sensitive transcription factors NF-κB and Nrf2 under conditions of chronic hypomelatoninemia and the exposure to the carbohydrate-lipid diet are effective means to restrain the development of oxidative-nitrosative stress in skeletal muscles.
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