Изучали влияние гидросульфида натрия — донатора сероводорода на параметры прооксидантно-антиоксидантного баланса у крыс при ишемии-реперфузии печени. Оценивали уровень продуктов перекисного окисления липидов (диеновые конъюгаты, малоновый диальдегид, основания Шиффа), факторов антиоксидантной системы (α-токоферол, ретинол, восстановленный глутатион, активность каталазы), маркеров повреждения печени — аланин- и аспартатаминотрансфераз. Установлено, что однократная инфузия гидросульфида натрия (14 мкмоль/кг за 5 мин до реперфузии) снижает уровень конечных продуктов перекисного окисления липидов в печени на 61,7 % (p = 0,0000007) и активность трансаминаз крови в среднем на 50,0 % (p = 0,000000002), повышает уровень ряда антиоксидантов в крови и печени в конце реперфузионного периода у экспериментальных животных. Защитное действие гидросульфида натрия может быть опосредовано модулирующим эффектом сероводорода на антиоксидантную систему, что снижает интенсивность окислительного стресса при ишемии-реперфузии печени у крыс.

Tissue relative "hyperoxia" during reperfusion can cause oxidative stress due to oxygen participation in free radical processes. The influence of the hydrogen sulfide on the blood oxygen was investigated during hepatic ischemia(30 min, m.Pringle) and reperfusion(120 min) in rats. The parameters of blood oxygen (р50, Hb, MetHb, HbCO, pCO2,pO2, pH, TCO2, ABE, SBC), summary nitrite/nitrate level, plasma hydrogen sulfide and transaminases (ALT, AST) as a marker of liver damage were estimated. It's detected, that a single injection of sodium hydrosulfide (14 μmol/kg, 5 min before reperfusion) improves blood oxygen parameters (p50, pH, TCO2, ABE, SBC), plasma hydrogen sulfide and decreases transaminase levels during hepatic ischemia-reperfusion in rats. It was no changes in the MetHb or HbCO concentrations after sodium hydrosulfide infusion. The protective effect of hydrogen sulfide can be bind with increased hemoglobin oxygen affinity in the blood during reperfusion.

The role of blood oxygen in the protective mechanism of ischemic preconditioning (IPC) was investigated in rabbits during hepatic ischemia-reperfusion (HIR). Animals were divided into 2 experimental groups: in the 1st group (n = 11) hepatic ischemia (30 min) was induced by Pringle maneuver, reperfusion was lasted 120 min; in the 2nd group (n = 8) the short period of vascular clamping (10 min) and reperfusion (10 min) were performed before HIR. The parameters of blood oxygen (рО2, p50, Hb), acid-base balance (рН, рСО2, TCO2, ABE, SBE, SBC and etc.), lipid peroxidation (Schiff bases, conjugated dienes), antioxidant system (catalase, α-tocopherol), plasma transaminases (ALT, AST) and nitrite/nitrate concentration (NOx) were measured. HIR in the 1st group leads to elevation of p50, lipid peroxidation, ALT and AST accompanied by reduction of рН, TCO2, ABE, SBE, SBC, catalase activity, α-tocopherol and NOx levels. IPC significantly reduces p50, lipid peroxidation, ALT and AST simultaneously improves рН, TCO2, ABE, SBC, catalase activity, α-tocopherol and NOx levels. These findings indicate that IPC prevents oxidative stress in liver trough increased blood hemoglobin-oxygen affinity and limitation of oxygen participation in free radical processes during reperfusion.

Oxidative damages are a key pathogenetical mechanism of hepatic ischemia-reperfusion syndrome. The aim of the review is to analyze the current concepts of the pathogenesis of oxidative stress in the liver during ischemia-reperfusion and the most effective approaches to the correction of this pathology. The possibility of using gasotransmitters as universal modulators of the redox state in post-ischemic tissues is given particular attention.

The antioxidant effect of melatonin on the blood oxygen transport and prooxidant-antioxidant balance during with hepatic ischemia-reperfusion (HIR) with inhibited NO synthase function has been studied in male Wistar rats. The animals were divided into 4 groups: (1) control; (2) hepatic ischemia (Pringle m., 30 min) and reperfusion for 120 min (HIR, n = 9); (9) HIR with melatonin (10 mg/kg, i.p., 10 min before HIR, n = 9); and (4) same with NO inhibitor (L-NAME, 10 mg/kg) added 5 min before melatonin administration. The indices of blood oxygen transport (p50act, pCO2, pH, pO2, etc.) and prooxidant-antioxidant balance (Schiff bases, conjugated dienes, catalase, retinol, alpha-tocopherol) were measured in blood and liver. HIR in group 1 resulted in higher p50act in mixed venous blood and sever oxidative disturbances: rise of CD and SB, decrease of alpha-T, Ret, and Cat. Melatonin in group 3 significantly improved these changes in p50act and prooxidant-antioxidant balance during HIR, but L-NAME in group 4 partly eliminated this effect. It is concluded that the antioxidant effect of melatonin during HIR is partly associated with NO-depended mechanisms, which can modify blood hemoglobin affinity to oxygen, thus limiting oxygen binding in free-radical processes.

The parameters of blood oxygen transport, the products of lipid peroxidation and antioxidative factors were determined in rats during the hepatic ischemia/reperfusion (HIR) under preliminary single injections of different doses ofrecombinant human erythropoietin (rhEPO). Hepatic ischemia was induced for 30 min by Pringle maneuver, reperfusion lasted 120 min. The experiments had shown that HIR led to the significant decreases in the hemoglobin oxygen affinity, activation of lipid peroxidation, depletion of the antioxidant system, increases blood transaminases (ALT and AST). rhEPO in dose 100 IU/kg aggravates decreasing hemoglobin oxygen affinity, improves some antioxidant parameters, but didn't correct lipid peroxidation or plasma transaminases during HIR. rhEPO infusion id dose 1000 IU/kg leads to oxyhemoglobin dissociative curve shift left-wards, improves prooxidant-antioxidant balance and plasma ALT, AST activities at the end of re-perfusion period.

The parameters of blood oxygen transport were determined in rabbits during the hepatic ischemia/reperfusion (HIR) with or without sodium nitroprusside (SNP) administration. Hepatic ischemia was induced for 30 min by a. hepatica propria clamping, reperfusion lasted 120 min. Indices of blood oxygen transport (hemoglobin-oxygen affinity index (p50), pO2, pH, pCO2, HCO3-, TCO2, ABE, etc.) and nitrite/nitrate (NO(x)) amounts were measured in blood during HIR. Animals were subdivided into two groups: 1st group--HIR; 2nd--HIR plus SNP infusion (SNP, Sigma, i.v. 10 mcmol/kg). The experiments had shown that HIR led to significant acidic changes in the acid-base balance and high blood p50. The SNP infusion in the 2nd group led to less changing in the p50 values during HIR which were accompanied with high NO(x) levels. We conclude that oxyhemoglobin dissociation curve shift leftwards after SNP administration promotes the maintenance liver during ischemia-reperfusion.

We have studied the effect of 1-methylnicotinamide (MNA) on prooxidant - antioxidant balance parameters by measuring the concentrations of lipid peroxidation products (conjugated dienes (CD) and Schiff bases (SB)) and antioxidant system factors (alpha-tocoferol (alpha-T), retinol (Ret) in the blood and liver homogenates and by evaluating the activity of catalase (Cat) and alanine and aspartate aminotransferases in the blood plasma in the course of hepatic ischemia-reperfusion in a group of 16 adult male Wistar rats (weighing 360-440 g). The anmals were divided into two groups: (1) hepatic ischemia (30 min, m. Pringle) and reperfusion (120 min) (HIR, n = 8); (2) HIR with MNA (100 mg/kg. i.p. 10 min before HIR, n = 8). In the first group, the plasma level of CD raised to 264.4% (p < 0.05), SB to 633.3% (p < 0.05), the concentration of alpha-T decreased by 19% (p < 0.05), that of Ret by 35.8 % (p < 0.05), and Cat by 45.8 % (p < 0.05) at the end of reperfusion as compared to control values before ischemia. In the second group, at the end of reperfusion the level of CD increased only to 51.4% (p < 0.05), SB to 130.3% (p < 0.05), Cat to 65% (p < 0.05), and the concentration of alpha-T in the plasma decreased only to 11% (p < 0.05), and Ret to 20.7% (p < 0.05). It is concluded that MNA significantly improves the prooxidant - antioxidant balance parameters during hepatic ischemia-reperfusion in rats.

The blood oxygen transport parameters were investigated in rats during hepatic ischemia-reperfusion under 1-methylnicotinamide administration. It has been determined that hemoglobin oxygen affinity significantly decreased in experimental animals after ischemia and at the end of reperfusion. It has been shown that in rats under 1-methylnicotinamide administration blood oxygen-binding properties changed less at the end of reperfusion period than in animals that didn’t receive the preparation. The role of blood oxygen transport function and possible mechanisms of 1-methylnicotinamide protective effect on the liver during ischemia-reperfusion are analyzed.

Parameters of blood oxygen transport in rabbits under nitroglycerine infusion were investigated under conditions of hepatic ischemia-reperfusion. The potential mechanisms of nitroglycerine protective influence on the liver under ischemia-reperfusion, realized through the system of oxygen transport, are analyzed. Pathophysiological aspects of hemoglobin oxygen affinity participation in hepatic injury development during ischemia-reperfusion in rabbits and nitric oxide role in this pathology are considered. We investigated the nitroglycerine influence on parameters of blood oxygen transport in rabbits with hepatic ischemia-reperfusion. These data suggested the important role of nitroglycerine in correction of blood oxygen transport parameters under hepatic ischemia-reperfusion.

Previous investigations indicated a protective effect of L-arginine (300 mg/kg) against hepatic reperfusion injury. This was an investigation of the mechanism of this protective effect. The infusion of L-arginine under the conditions of inhibited NO synthesis (L-NAME, 10 mg/kg) significantly increased lipid peroxidation processes and transaminase activity and decreased antioxidant defense in postischemic liver. It is concluded that protective mechanism of L-arginine against hepatic reperfusion injury is associated with NO synthesis.

The disbalance between reactive oxygen species generation and antioxidant defensive factors importantly contributes in the development of hepatic reperfusion damage. Changes in blood oxygen transport during hepatic ischemia/reperfusion are involved in its development. Ischemia-induced oxyhemoglobin dissociation curve shift rightwards also exists during the hepatic reperfusion and thereby may facilitate the free radical attacks against the liver. The least disorders in blood oxygen transport, prooxidant-antioxidant balance and hepatic morpho-functional state were observed during the postischemic period under the conditions of moderate hypoxia. The protective effect of L-arginine during the hepatic ischemia-reperfusion may be partially due to the changed hemoglobin function and thereby tissue oxygen delivery and to the keeping of body prooxidant-antioxidant balance. The development of new pharmacological tools to modify the blood oxygen transport and generate the optimal nitric oxide amounts may be a promising strategy for correction of reperfusion injury.

The effect of nitroglycerine on some parameters of the prooxidant-antioxidant balance and functional state of the liver under conditions of ischemia/reperfusion was studied on rabbits. Hepatic ischemia/reperfusion was accompanied by accumulation of LPO products, depletion of the antioxidant defense system, and increase in blood transaminase activity. Nitroglycerine infusion before the reperfusion period decreased the concentration of LPO products, increased activity of the antioxidant system, and improved liver function.

The L -arginine-NO system functioning in rabbits with hepatic ischemia and reperfusion was modified by infusing the NO synthase (NOS) inhibitor N G -nitro- L -arginine (15 mg/kg) or the NOS substrate L -arginine (300 mg/kg). The effect was evaluated by determining the lipid peroxidation (LPO) products (conjugated dienes, Schiff bases) and antioxidant system factors (α-tocopherol, retinol, catalase activity factor). The degree of reperfusive damage was evaluated by the alanine amino transferase (AlAT) and aspartate amino transferase (AsAT) activity in the blood of experimental animals. The development of ischemia and reperfusion leads to a significant growth in the LPO rate, depletion of the antioxidant system factors in the blood and liver tissue, and increase in the AlAT and AsAT activity. The L -arginine infusion prior to the reperfusion period decreased violation of the prooxidant - antioxidant state and favored normalization of the AlAT and AsAT activity in the blood. No such effects were observed as a result of the NOS inhibition prior to the onset of ischemia.

The L-arginine--NO system functioning in rabbits with hepatic ischemia and reperfusion was modified by infusing the NO synthase (NOS) inhibitor NG-nitro-L-arginine (15 mg/kg) or the NOS substrate L-arginine (300 mg/kg). The effect was evaluated by determining the lipid peroxidation (LPO) products (conjugated dienes, Schiff bases) and antioxidant system factors (alpha-tocopherol, retinol, catalase activity factor). The degree of reperfusive damage was evaluated by the alanine amino transferase (AlAT) and aspartate amino transferase (AsAT) activity in the blood of experimental animals. The development of ischemia and reperfusion leads to a significant growth in the LPO rate, depletion of the antioxidant system factors in the blood and liver tissue, and increase in the AlAT and AsAT activity. The L-arginine infusion prior to the reperfusion period decreased violation of the prooxidant-antioxidant state and favored normalization of the AlAT and AsAT activity in the blood. No such effects were observed as a result of the NOS inhibition prior to the onset of ischemia.

Indices of blood oxygen transport (hemoglobin-oxygen affinity, pCO2, pH, pO2, etc.) and prooxidant-antioxidant state (Schiff bases, conjugated dienes, catalase, retinal, alpha-tocopherol) were measured in rabbit blood and the liver during postischemic reperfusion. Hepatic ischemia was induced for 30 min by ligation of a hepatica propria, and reperfusion lasted for 120 min. Hepatic ischemia worsened blood oxygen transport. Restoration of arterial blood flow did not result in improvement of oxygen delivery. Moreover, marked metabolic acidosis was observed throughout 2 hr of reperfusion. Ischemia induced a shift of oxyhemoglobin dissociation curve to the right. This shift persisted after restoration of hepatic arterial blood flow facilitating increased oxygen transport to tissues. Changes in blood oxygen transport during hepatic ischemia/reperfusion were accompanied with high activity of free radical processes. During reperfusion, the largest increase in content of lipid peroxidation products and the greatest fall of some antioxidant levels except catalase were observed indicating impairment of liver prooxidant-antioxidant balance. The results showed that activation of lipid peroxidation and a decrease in some antioxidant levels during hepatic reperfusion were associated with lowering of hemoglobin-oxygen affinity and suggest participation of the latter in impairment of prooxidant-antioxidant balance.