Betulin, a pentacyclic triterpene, possesses antioxidant, anti-inflammatory and hepatoprotective properties. The aim of this study was to evaluate the impact of liver mitochondria in hepatoprotection of betulin using a rat model of alcoholic steatohepatitis induced by ethanol administration (4 g/kg, intragastric) for 8 weeks. The treatment with betulin (50 and 100 mg/kg b.w., intragastric) during this period attenuated the histological signs of steatohepatitis and lowered the serum and liver triglyceride contents, as well as the serum activities of aspartate aminotransferase, alanine aminotransferase, and alkaline phosphatase. Betulin (100 mg/kg) decreased the liver/body weight ratio and inhibited the increase in the serum levels of TNFα, IL-1β, TGFβ, and hyaluronic acid, demonstrating hepatoprotective, anti-inflammatory, and antifibrotic potential. Betulin also inhibited the formation of superoxide anions in mitochondria and the end-products of lipid peroxidation in liver tissue, the amount of which was significantly increased in ethanol-treated rats. The disturbances in mitochondrial respiration, uncoupling of oxidative phosphorylation and decreasing of mitochondrial complex I, II, and IV activities in rats with steatohepatitis, were reverted by betulin administration. The increased susceptibility of mitochondria to Ca2+-induced permeability transition pore formation in the hepatitis group was improved in rats treated with betulin. In conclusion, betulin, having antioxidant properties, exerts a beneficial effect in the rat model of alcoholic steatohepatitis via prevention of liver mitochondria dysfunction, which may be attributed to the inhibition of mitochondrial permeability transition.

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Aim The liver is the main target for alcohol-induced injury. The aims of this work were to carry out further research into the mechanisms of liver damage induced by long-term administration of high-dose ethanol to rats and to evaluate the hepatoprotective potential of red cabbage (Brassica oleracea var. capitata f. rubra) anthocyanins (RCE). Material/Methods Male albino Wistar rats were divided into four groups. Group 1 was the control. Groups 2 through 4 received ethanol (4 g/kg body weight, 8 weeks). Group 3 received 11 mg RCE/kg and Group 4 received 22 mg RCE/kg. Dry lyophilised RCE was prepared from fresh red cabbage and analysed. We then evaluated the liver histology, mitochondrial respiration, and biochemical and immunological parameters in these groups of rats. Results The rat intoxication caused steatohepatitis characterised by macro- and microvesicular steatosis, ballooning and fatty liver dystrophies, lymphocytic infiltration, neutral lipid accumulation, and elevations of the serum activities of the liver injury marker enzymes. The treatment of alcohol-administered rats with RCE (mainly, cyanidin-3-diglucoside-5-glucoside, cyanidin-3-coumaroylrutinoside-5-hexoside, cyanidin-3-feruloylrutinoside-5-hexoside, delphinidin-3-feruloylrutinoside-hexoside) dose-dependently alleviated these pathological changes: The sizes of hepatocyte lipid vacuoles and the inflammatory signs were decreased, and the levels of the rat serum biochemical markers of liver injury, proinflammatory cytokines TNFα and IL-6, and the adipokine leptin (and not TGFβ) were significantly reversed. The RCE administration during intoxication completely recovered the changed liver mitochondria respiration rates and the ADP/O coefficient, as well as the phagocytic index and neutrophil metabolic activity in the blood. In experiments in vitro, RCE (13.6 μg/ml) modulated the respiratory parameters of isolated rat liver mitochondria, dissipated mitochondrial membrane potential, and inhibited the Ca2+-induced mitochondrial permeability transition. Conclusion The red cabbage anthocyanins could be useful for treatment of alcoholic liver injury due to their Ca2+-ionophoric/protonophoric activity, influence on Ca2+ homeostasis, and improving mitochondrial functions and inflammatory status.

Институт биохимии биологически активных соединений Национальной академии наук Беларуси, Гродно, Беларусь Введение. Печёночная энцефалопатия (ПЭ) является наиболее тяжёлым осложнением как острой, так и хронической печёночной недостаточности. Спектр современной фармакотерапии ПЭ ограничен, поэтому поиск дополнительных альтернативных средств для лечения этой патологии актуален. Цель исследования-оценка эффективности применения S-аденозилметионина (SAM) в коррекции экспериментальной ПЭ у крыс. Материалы и методы. В качестве источника SAM применяли отечественный препарат ГепталНАН (Академфарм, Минск). В опыте использовали крыс с ПЭ, индуцированной введением тиоацетамида (350 мг/ кг, в/бр, в течение 3 дней). Препарат SAM в двух дозах (200 и 400 мг/кг) вводили 4-кратно внутрижелудочно. Для оценки фармакологического эффекта SAM использовали поведенческие тесты, гистологические и биохимические методы исследования. Результаты. Введение SAM улучшало поведенческие реакции животных с ПЭ, снижало уровень аммиака и продуктов азотистого обмена в сыворотке крови, демонстрировало гепатопротективный и антиоксидантный эффекты. Низкая доза SAM (200 мг/кг) снижала смертность у крыс, получавших ТАА, уменьшала содержание ФНО-α в сыворотке крови. Заключение. Препарат SAM в условиях экспериментальной ПЭ оказывал защитное действие, улучшая поведенческие реакции, снижая уровень аммиака в крови и оказывая гепатопротективное и антиоксидантное действие.