Efficacy of hesperidin on plasma,heart and liver tissue lipids in rats subjected to isoproterenol-induced cardiotoxicity

The present study examines the preventive role of hesperidin (HDN) on plasma, cardiac and hepatic lipids in isoproterenol (ISO)-induced rats. Myocardial injury was induced by subcutaneous injection of isoproterenol hydrochloride (85 mg/kg BW) twice at an interval of 24 h, for two consecutive days. HDN was administered by post-orally at a dose of 200 mg/kg BW. The results showed increased levels of plasma cholesterol, low density lipoprotein-cholesterol (LDL-C), very low density lipoprotein-cholesterol (VLDL-C), triglycerides (TG), free fatty acids (FFA) and phospholipids (PL) and decreased level of high density lipoprotein-cholesterol (HDL-C) in ISO-induced rats. ISO rats also showed an increase in cholesterol, TG and FFA and decrease in PL levels in the heart and liver tissues. HDN treatment brought the above parameters towards normal level. This experiment shows that HDN possesses hypolipidemic effect in ISO-induced rats.     

Symplocos cochinchinensis attenuates streptozotocin-diabetes induced pathophysiological alterations of liver,kidney, pancreas and eye lens in rats

The beneficial effects of hydroethanol extract of Symplocos cochinchinensis (SCE) has been explored against hyperglycemia associated secondary complications in streptozotocin induced diabetic rat model. The experimental groups consist of normal control (NC), diabetic control (DC), DC + metformin 100 mg kg⁻¹ bwd, DC + SCE 250 and DC + SCE 500. SCEs and metformin were administered daily for 21 days and sacrificed on day 22. Oral glucose tolerance test, plasma insulin, % HbA1c, urea, creatinine, aspartate aminotransferase, alanine aminotransferase, albumin, total protein etc. were analysed. Aldose reductase (AR) activity in the eye lens was also checked. On day 21, DC rats showed significantly abnormal glucose response, HOMA-IR, % HbA1c, decreased activity of antioxidant enzymes and GSH, elevated AR activity, hepatic and renal oxidative stress markers like malondialdehyde, protein carbonyls compared to NC. DC rats also exhibited increased level of plasma urea and creatinine. Treatment with SCE protected from the deleterious alterations of biochemical parameters in a dose dependent manner including histopathological alterations in pancreas. SCE 500 exhibited 46.28% of glucose lowering effect and decreased HOMA-IR (2.47), % HbA1c (6.61), lens AR activity (15.99%), and hepatic, renal oxidative stress and function markers compared to DC group. Considerable amount of liver and muscle glycogen was replenished by SCE treatment in diabetic animals. Although metformin showed better effect, the activity of SCE was very much comparable with this drug.     

Changes in creatine kinase activity in the brain,heart, liver,and blood plasma of hypoxia rats

The effect of hypoxic and cytotoxic hypoxia on creatine kinase (CK) activity of the blood plasma, the brain, heart, and liver tissues, and the nuclear and mitochondrial fractions of the brain was studied. Hypoxia causes marked changes in CK activity of all the tissues and organelles studied. The magnitude and direction of the changes in CK activity depend on the type and duration of hypoxia, the organ-specificity of the CK, and disturbance of the permeability of cell membranes.Laboratory of Physiology of the Cerebral Circulation, A. L. Polenov Neurosurgical Institute, Leningrad. (Presented by Academician of the Academy of Medical Sciences of the USSR V. N. Chernigovskii). Translated from Byulleten' Éksperimental'noi Biologii i Meditsiny, Vol. 81, No. 2, pp. 177–179, February, 1976.     

Comparison of lipid peroxidation parameters in the heart,liver, and brain of rats with different degrees of resistance to hypoxia

The relationship between the intensity of lipid peroxidation and the activity of the antioxidant system in the heart, liver, and brain is studied in male Wistar rats with low and high resistance to hypoxia tested by being “raised” to an altitude of 11.5 km and in intact outbred rats. It is found that in all groups of rats the content of lipid peroxidation products is highest in the liver, lower in the heart, and lowest in the brain. In all groups, the rate of the ascorbate-induced lipid peroxidation is highest in the brain, lower in the liver, and lowest in the heart. The activity of the antioxidant system is highest in the brain, lower in the liver, and lowest in the heart of low-resistance and outbred rats, while in high-resistance rats it is the same in all the organs. Thus, the difference in the parameters of lipid peroxidation and, particularly, of the antioxidant system in the studied organs is most pronounced in rats with a low resistance to hypoxia. Translated fromByulleten' Eksperimental'noi Biologii i Meditsiny, Vol. 121, N ^o 2, pp. 138–143, February, 1996 Presented by A. I. Archakov, Member of the Russian Academy of Medical Sciences     

败血症大鼠肝,肾,心,肺线粒体功能的变化

本实验根据Wichterman等人方法建立盲肠结扎穿孔(CLP)败血症大鼠模型,观察了CLP败血症早、晚期心、肺、肝和肾线粒体功能的变化。CLP12h,肝、肾和心线粒体呼吸控制率(RCR)较对照组明显降低(分别为P<0.001,P<0.05,P<0.01)。CLP16h,肺线粒体RCR亦有明显降低(P<0.001)。各生命脏器线粒体P/O值也都较对照组显著下降(P<0.001)。CLP20h,RCR和P/O都下降更甚。结果提示CLP败血症过程中,生命脏器线粒体损伤的广泛性和严重性,生命脏器线粒体损伤可能是败血症过程中多种器官功能衰竭的始动环节,线粒体的损伤可能与细菌和/或内毒素的直接作用有关。     

Proteomic analysis of mitochondrial proteins in cardiomyocytes from rats subjected to intermittent hypoxia

Intermittent hypoxia (IH) markedly enhances cardiac tolerance against ischemia/reperfusion injury, but its mechanism and molecular basis remain unclear. For exploring the expression of mitochondrial proteins induced by IH, two-dimensional electrophoresis and Thermo Finnigan LTQ mass spectrometer (MS) were applied. After comparing the protein profiles of myocardial mitochondria between IH and normoxic hearts, 14 protein spots were found to be altered more than threefold between the two groups, 11 of which were identified by Finnigan LTQ MS. Among these 11 proteins, 9 were involved in energy metabolism, including 7 that were increased after IH. The latter were identified as aldehyde dehydrogenase, methylmalonate-semialdehyde dehydrogenase, ATP synthase β chain, mitochondrial aconitase, malate dehydrogenase, electron transfer flavoprotein α subunit and sirtuin 5. Two other proteins, ubiquinol-cytochrome C reductase iron-sulfur subunit and aspartate aminotransferase, were decreased after IH. Biochemical tests for energy metabolism in mitochondria supported the proteomic results. IH exposure also increased the expression of a molecular chaperone—heat shock protein 60 and an antioxidant protein, peroxiredoxin 5. These findings will provide clues for understanding the mechanism of IH-induced cardiac protection and may lead to the development of interventional strategies designed to utilize the advantages of IH clinically.     

Organ-specific characteristics of blood supply in the liver, kidney, and brain in acute blood loss in rats with various resistance to circulatory hypoxia

A marked fall in arterial blood pressure, organ blood flow rates and tissue perfusion in the liver, kidneys and brain was registered by ultrasound and laser Doppler flowmetry in rats with low (LR) and high resistance (HR) to circulatory hypoxia (average life spans less than 1.5 h and more than 3 h were 42 and 58%, respectively) at the end of acute massive hemorrhage. In the posthemorrhagic period organ hemodynamics and microcirculation showed a tendency to further decrease in LR rats. In HR rats blood flow in hepatic, renal and common carotid arteries were restored for a while up to 115-120%, 85-90% and 60-65%, respectively, following bleeding arrest. At this new posthemorrhagic level the brain flow was actively maintained in the compensatory phase of the posthemorrhagic period due to autoregulatory changes in the carotid resistance. Such a peculiar reaction of the brain blood vessels in HR rats is considered as an adaptive response protecting the brain during massive hemorrhage under severe tissue hypoxia against autoreperfusion and reoxygenation-induced damage.     

Diet restriction plays an important role in the alterations of heart mitochondrial function following exposure of young rats to chronic hypoxia

Male Wistar rats aged 4 weeks, were subjected to hypobaric hypoxia (barometric pressure 505 hPa, PI,O2 106 hPa) or to diet restriction (reproducing the effect of hypoxia-induced anorexia) for 4 weeks. Each group (control, hypoxic, pair-fed, n = 16), was divided into two sub-groups housed individually in either normal cages or cages with running wheels allowing evaluation of voluntary activity (n = 8 each). The skinned-fibre technique was used to evaluate the functional properties of myofibrillar mitochondria from right and left ventricles in situ. The oxidative fibres from the soleus and diaphragm muscles were also investigated for comparison. Analysis of variance did not detect any significant effect of voluntary running activity. With calorie restriction, the maximal respiratory rate (Vmax) in the presence of 1 mM adenosine 5'-diphosphate (ADP) in myocardial fibres fell significantly (by about 25%) but was unchanged in skeletal myocytes. Following hypoxia, Vmax in myocardial fibres increased by 25% compared with the calorie restricted group and in soleus and diaphragm muscle fibres by about 30% compared with control. In myocardial fibres of control rats, creatine (20 mM) increased the sub-maximal respiratory rate by 80% in the presence of 0.1 mM ADP. Under calorie restriction or hypoxia the stimulatory effect was significantly reduced to 34-56%. This alteration was due to a decrease in the apparent Michaelis-Menten constant (Km) of mitochondrial respiration for ADP evaluated in the absence of creatine, while the Km in presence of creatine 20 mM was unchanged. In conclusion, reduced food intake decreased the oxidative capacity (Vmax) and the apparent Km for ADP of mitochondria in both left and right ventricles. Chronic hypoxia per se was responsible for an increase in the oxidative capacity of all oxidative muscles but did not exert significant effects on the control of respiration by ADP and creatine in myocardium.     

Changes in the liver of rats exposed in utero to chronic hypoxia

Central Research Laboratory, Khabarovsk Medical Institute. (Presented by Academician of the Academy of Medical Sciences of the USSR S. V. Severin.) Translated from Byulleten' Éksperimental'noi Biologii i Meditsiny, Vol. 110, No. 11, pp. 541–543, November, 1990.     

The oxidant and antioxidant effects of 25-hydroxyvitamin D3 in liver, kidney and heart tissues of diabetic rats

Abstract Previous studies have implicated protective effects of vitamin D on insulin secretion and pancreas cell function. The goal of the present study is to determine if a combination therapy of 25-hydroxyvitamin D3 and insulin had any advantage over insulin therapy alone on lipid peroxidation and antioxidant activity in the streptozotocin (STZ)-induced diabetic rat. The lipid peroxidation product, thiobarbituric acid-reacting substances (TBARS), was measured to assess free radical activity in the heart, kidney and liver tissues. The enzymatic activities of glutathione peroxidase (GSH-Px), superoxide dismutase (SOD) and catalase (CAT) were measured as indicators of antioxidation in these tissues. Sprague-Dawley rats were made diabetic with a single injection of STZ (75 mg/kg i.p.). Rats were separated into three groups, each containing 10 animals: Group 1, non-diabetic and no drug treatment was given; Group 2, diabetic rats were treated with 3 IU/day subcutaneous (s.c.) insulin; and Group 3, diabetic rats were treated with 3 IU/day (s.c.) insulin plus 1 mg/kg/day per oral (p.o.) 25-hydroxyvitamin D3 for a period of 4 weeks. At the end of the study, TBARS contents of the liver, kidney and heart tissues in Groups 2 and 3 were found to be significantly increased as compared to Group 1 (P<0.05) and kidney MDA levels in Group 3 were also significantly increased as compared to Group 2 (P<0.05). The SOD and CAT contents of the heart in Group 2 were significantly increased as compared to Groups 1 and 3 (P<0.05). GSH-Px activity was unaltered in all groups (P>0.05). We suggest that a combination of insulin with 25-hydroxyvitamin D3 treatment would not be more beneficial than the use of insulin alone in antioxidant defence of diabetic liver and kidney tissues.     

Localization of purine and pyrimidine nucleoside phosphorylases in heart, kidney, and liver

In isolated livers and kidneys perfused with Krebs-Henseleit solution, the relationship of the concentration of adenosine (Ado) to that of its degradation products inosine (Ino) and hypoxanthine (Hyp) in biliary, urinary, and venous effluents were determined. They revealed ratios of Hyp:Ado:Ino, 1.9:1:0.9, 0.7:1:0.6, and 1.3:1:0.5 for guinea pig biliary, guinea pig urinary, and rat urinary effluents, respectively, and their respective venous effluent were 58:1:29, 8.6:1:5.4, and 7.4:1:3.2. The greater proportion of Ino and Hyp in the venous effluents suggests active production in Ino and Hyp at the vessel wall. Purine nucleoside phosphorylase localization was determined histochemically and found most active in the cytoplasm of capillary endothelium and Kupffer cells. Thus, there is agreement between purine analysis and histochemical findings. The reliability of the histochemical technique was also tested by comparing activities of purine nucleoside phosphorylase (a cytoplasmic enzyme) and pyrmidine nucleoside phosphorylase (a nuclear enzyme) that catalyze similar reactions (nucleoside + inorganic phosphate in equilibrium base + ribose-1-phosphate) but with different base specificites and cellular localization, as indicated by cell fractionation studies. The histochemical results show that in contrast to the purine nucleoside phosphorylase, the pyrmidine specific enzyme was most active in the nuclei of endothelial and Kupffer cells. Thus, the technique discriminates between the two enzymes.