The effects of exercise on lipogenic enzyme activity and glyceride synthesis by liver homogenates of diabetic rats

The purpose of this study was to determine if exercise ameliorates the elevated levels of triglycerides in diabetic rats and also to determine if the capacity of liver to synthesize glycerides correlates with changes in plasma triglyceride levels. Forty female rats were divided into four groups: sedentary control, sedentary diabetic, exercised control, and exercised diabetic. Diabetes was induced by intravenous injection of alloxan (40 mg/kg), and control rats were sham-dosed with physiologic saline. All rats remained sedentary in their cages for the first week after the injections. The exercised groups were exercised for seven consecutive days for 2 h/d at 20 m/min (0 grade). All rats were killed 24 hours after the last exercise bout. Blood glucose levels were significantly higher in the diabetic group than the nondiabetic counterparts, but exercise did not affect glucose levels in either the diabetic or nondiabetic groups. Exercise, however, significantly lowered plasma triglyceride and free fatty acid levels in both diabetic and nondiabetic rats. The activities of the five enzymes involved in fatty acid synthesis were all depressed in the diabetic rats compared to controls, and exercise had no effect on the activities of the enzymes. The capacity of liver to synthesize total lipids, diglycerides, or triglycerides was not different in the diabetic rats from that of nondiabetic rats, and exercise did not change that. Only phospholipid synthesis from glycerol-3-phosphate was affected by diabetes. It is concluded that exercise ameliorates the elevations in plasma triglyceride levels that result from diabetes.(ABSTRACT TRUNCATED AT 250 WORDS)     

Remote ischemic preconditioning protects liver ischemia-reperfusion injury by regulating eNOS-NO pathway and liver microRNA expres-sions in fatty liver rats

BACKGROUND: Ischemic preconditioning (IPC) is a strategy to reduce ischemia-reperfusion (I/R) injury. The protective effect of remote ischemic preconditioning (RIPC) on liver I/R injury is not clear. This study aimed to investigate the roles of RIPC in liver I/R in fatty liver rats and the involvement of en-dothelial nitric oxide synthase-nitric oxide (eNOS-NO) path-way and microRNA expressions in this process. METHODS: A total of 32 fatty rats were randomly divided into the sham group, I/R group, RIPC group and RIPC+I/R group. Serum alanine aminotransferase (ALT), aspartate ami-notransferase (AST) and nitric oxide (NO) were measured. Hematoxylin-eosin staining was used to observe histological changes of liver tissues, TUNEL to detect hepatocyte apoptosis, and immunohistochemistry assay to detect heat shock protein 70 (HSP70) expression. Western blotting was used to detect liver inducible NOS (iNOS) and eNOS protein levels and real-time quantitative polymerase chain reaction to detect miR-34a, miR-122 and miR-27b expressions. RESULTS: Compared with the sham and RIPC groups, serum ALT, AST and iNOS in liver tissue were significantly higher in other two groups,while serum NO and eNOS in liver tissue were lower, and varying degrees of edema, degeneration and in-flammatory cell infiltration were found. Cell apoptosis num-ber was slightly lower in the RIPC+I/R group than that in I/R group. Compared with the sham group, HSP70 expressions were significantly increased in other three groups (all P<0.05). Compared with the sham and RIPC groups, elevated miR-34a expressions were found in I/R and RIPC+I/R groups (P<0.05). MiR-122 and miR-27b were found significantly decreased in I/R and RIPC+I/R groups compared with the sham and RIPC groups (all P<0.05). CONCLUSION: RIPC can reduce fatty liver I/R injury by affect-ing the eNOS-NO pathway and liver microRNA expressions.     

Liver Microsomal Fatty Acid Composition in Ethanol-Fed Rats: Effect of Different Dietary Fats and Relationship to Liver Injury

The rat intragastric feeding model for alcoholic liver disease was used to study the effect of different diets on the fatty acid composition of liver microsomes. Rats were fed corn oil and ethanol (CE), saturated fat and ethanol (SF+E) or corn oil and dextrose (CD) for either 2 or 4 weeks. Rats were also fed saturated and dextrose (SF+D) for 4 weeks. In comparison with the CD diet, lower levels of arachidonic acid were detected in rats fed the CE, SF+E, and SF+D diets. However, the diet-induced changes in levels of arachidonic acid varied as a function of length of feeding. In rats fed the CE diet, we detected a significant decrease in the level of arachidonic acid compared with CD animals. Conversely, in rats fed the SF+E diet, the level of arachidonic acid increased compared with the SF+D group. In addition, a significant correlation was noted between levels of oleic acid and arachidonic acid in both corn oil ( r =–0.85, p < 0.01) and saturated fat ( r =–0.76, p < 0.05) groups. However, the changes in levels of arachidonic acid and oleic acid were in opposite directions in the two groups. Levels of docosahexaenoic acid decreased between the 2 and 4 weeks in animals maintained on the CE diet. Levels of stearic acid increased between 2 and 4 weeks in rats fed the SF+E diet. The lowest level of linoleic acid was detected in the SF+D and SF+E groups, but levels of linoleic acid remained constant in all groups throughout the study. Histological evaluation indicated that ethanol-induced liver injury was limited to rats fed the diet containing corn oil for 4 weeks. Thus, diet-dependent differences in liver microsomal fatty acid composition may help to explain why ethanol-induced liver injury occurs in rats fed corn oil, but not saturated fat.     

Exercise at anaerobic threshold intensity and insulin secretion by isolated pancreatic islets of rats

To evaluate the effect of acute exercise and exercise training at the anaerobic threshold (AT) intensity on aerobic conditioning and insulin secretion by pancreatic islets, adult male Wistar rats were submitted to the lactate minimum test (LMT) for AT determination. Half of the animals were submitted to swimming exercise training (trained), 1 h/day, 5 days/week during 8 weeks, with an overload equivalent to the AT. The other half was kept sedentary (sedentary). At the end of the experimental period, the rats were submitted to an oral glucose tolerance test and to another LMT. Then, the animals were sacrificed at rest or immediately after 20 minutes of swimming exercise at the AT intensity for pancreatic islets isolation. At the end of the experiment mean workload (% bw) at AT was higher and blood lactate concentration (mmol/L) was lower in the trained than in the control group. Rats trained at the AT intensity showed no alteration in the areas under blood glucose and insulin during OGTT test. Islet insulin content of trained rats was higher than in the sedentary rats while islet glucose uptake did not differ among the groups. The static insulin secretion in response to the high glucose concentration (16.7 mM) of the sedentary group at rest was lower than the sedentary group submitted to the acute exercise and the inverse was observed in relation to the trained groups. Physical training at the AT intensity improved the aerobic condition and altered insulin secretory pattern by pancreatic islets.     

藏红花对酒精及酒精加四氯化碳所致大鼠肝损伤的防治作用

目的：探索藏红花对酒精及酒精四氯化碳所致大鼠肝损伤的防治作用。方法：取Wistar雄性大鼠设5组,分别灌胃生理盐水（A）、白酒（B）、白酒加藏红花（C）,白酒加CCl4(D),在D组基础上加用藏红花（E）对5组大鼠血清ALT和肝脏组织学病变进行比较。结果：藏红花能降低白酒和四氯化碳引起的ALT升高（P＜0．05）;B、C组及D、E组互比肝脏组织学改变有明显差异（P＜0．05）。结论：藏红花对酒精及酒精四氯化碳所致肝损伤有一定的防治作用。     

Exercise training increases the activity of pyruvate dehydrogenase complex in skeletal muscle of diabetic rats

The effects of diabetes and exercise training on the activity of pyruvate dehydrogenase (PDH) complex in skeletal muscle were examined in rats. Male Sprague-Dawley rats were divided into four groups as follows: non-diabetic sedentary, non-diabetic trained, diabetic sedentary, and diabetic trained groups. Diabetic rats were prepared by a bolus injection of intravenous streptozotocin (50 mg/kg body weight). Exercise training was performed by having rats run on a treadmill at a speed of 25 m/min for 45 min/day, 6 days/wk for 4 wks. Exercise training decreased serum concentrations of glucose and non-esterified fatty acid in diabetic rats. GLUT4 content in skeletal muscle in sedentary rats was significantly decreased by diabetes; however, exercise training significantly increased the GLUT4 content in diabetic rats. The total and actual activities and the proportion of actual activity of the PDH complex were decreased in diabetic sedentary rats. Exercise training did not affect the total activity of the PDH complex in non-diabetic rats, whereas it increased the total activity in diabetic rats to the same level as that in non-diabetic rats. In diabetic rats, exercise training tended to increase the proportion of actual activity of the PDH complex from 2.7 +/- 0.4% to 4.7 +/- 0.8%, although the proportion of actual activity in non-diabetic rats was decreased by exercise training. The present study suggests that exercise training may improve glucose metabolism in the skeletal muscle of streptozotocin-induced diabetic rats probably through the mechanisms of increasing both GLUT4 content and the activity of the PDH complex.     

The Effect of a Silybin-Vitamin E-Phospholipid Complex on Nonalcoholic Fatty Liver Disease: A Pilot Study

Oxidative stress leads to chronic liver damage. Silybin has been conjugated with vitamin E and phospholipids to improve its antioxidant activity. Eighty-five patients were divided into 2 groups: those affected by nonalcoholic fatty liver disease (group A) and those with HCV-related chronic hepatitis associated with nonalcoholic fatty liver disease (group B), nonresponders to treatment. The treatment consisted of silybin/vitamin E/phospholipids. After treatment, group A showed a significant reduction in ultrasonographic scores for liver steatosis. Liver enzyme levels, hyperinsulinemia, and indexes of liver fibrosis showed an improvement in treated individuals. A significant correlation among indexes of fibrosis, body mass index, insulinemia, plasma levels of transforming growth factor-β, tumor necrosis factor-α, degree of steatosis, and γ-glutamyl transpeptidase was observed. Our data suggest that silybin conjugated with vitamin E and phospholipids could be used as a complementary approach to the treatment of patients with chronic liver damage. Other members of the Real Sud Group: L. Cimino, Federico II University, Naples; V. De Girolamo and A. Marone, Ascalesi Hospital, Naples; C. De Stefano, S. Carlo Hospital, Potenza; G. De Stefano, Madonna delle Grazie Hospital, Matera; D. Disalvo and B. Provenzano, Villa D’Agri Hospital, Potenza; P. Esposito and A. Simonetti, Second University, Naples; M. D. Iannece and R. Pempinello, Cotugno Hospital, Naples; R. Iorio, Giugliano Hospital, Naples; S. Monastra and M. Di Pierro, S. Gennaro Hospital, Naples.     

Protective effect of some vitamins against the toxic action of ethanol on liver regeneration induced by partial hepatectomy in rats

AIM： To investigate the effects of vitamins （A, C and E） on liver injury induced by ethanol administration during liver regeneration in rats. METHODS： Male Wistar rats subjected to 70% partial hepatectomy were divided into five groups （groups 1-5）. During the experiment, animals of Group 1 drank only water. The other four groups （2-5） drank 30 mL of ethanol/L of water. Group 3 additionally received vitamin A, those of group 4 vitamin C and those of group 5 received vitamin E. Subsequently serum alanine aminotransferase （ALT）, aspartate aminotransferase （AST）, albumin and bilirubin were measured colorimetrically. Lipid peroxidation （thiobarbituric-acid reactive substances, TBARS） both in plasma and liver was measured, as well as liver mass gain assessment and total DNA. RESULTS： Compared with sham group, serum AST and ALT increased significantly under ethanol treatment （43% and 93%, respectively, with P 〈 0.05）. Vitamin C and vitamin E treatment attenuated the ethanol-induced increases in ALT and AST activity. Ethanol treatment also decreased serum albumin concentration compared to sham group （3.1 ± 0.4 g/dL vs 4.5 ± 0.2 g/dL; P 〈 0.05）. During liver regeneration vitamins C and E significantly ameliorated liver injury for ethanol administration in hepatic lipid peroxidation （4.92 nmol/mg and 4.25 nmol/mg vs 14.78 nmol/mg, respectively, with P 〈 0.05）. In association with hepatic injury, ethanol administration caused a significant increase in both hepatic and plasma lipid peroxidation. Vitamins （C and E） treatment attenuated hepatic and plasma lipid peroxidation. CONCLUSION： Vitamins C and E protect against liver injury and dysfunction, attenuate lipid peroxidation, and thus appear to be significantly more effective than vitamin A against ethanol-mediated toxic effects during liver regeneration.     

Markedly Enhanced Cytochrome P450 2E1 Induction and Lipid Peroxidation Is Associated with Severe Liver Injury in Fish Oil—Ethanol-Fed Rats

We evaluated the role of changes in cytochrome P-450 2E1 (CYP 2E1) and lipid peroxidation in relation to development of severe liver injury in fish oil–ethanol-fed rats. The experimental animals (male Wistar rats) were divided into 5 rats/group and were fed the following diets for 1 month: corn oil and ethanol (CO+E) or corn oil and dextrose (CO+D), and fish oil and ethanol (FO+E) or fish oil and dextrose (FO+D). For each animal, microsomal analysis of CYP 2E1 protein, aniline hydroxylase activity, fatty acid composition, and conjugated dienes was conducted. Also, evaluation of severity of pathology was done for each rat. The mean ± SD of the pathology score was significantly higher ( p < 0.01) in the FO+E (6.0 ± 1.3) group than in the CO+E group (3.0 ± 0.5). No pathological changes were evident in the dextrose-fed controls. The CYP 2E1 protein levels (mean ± SD) were significantly higher ( p < 0.01) in the FO+E group (13.1 ± 2.0) compared with the CO+E (4.7 ± 1.2) and FO+D (1.8 ± 0.5) groups. Higher levels of eicosapentaenoic and docosa-hexaenoic acids and lower levels of arachidonic acid were detected in liver microsomes from rats fed fish oil compared with corn oil. A significant correlation was obtained between CYP 2E1 protein and conjugated diene levels ( r = 0.78, p < 0.01). Our results showing markedly increased CYP 2E1 induction and lipid peroxidation in the FO+E group provides one possible explanation for the greater severity of liver injury in this group.     

The Effects of Rosiglitazone,Metformin, and Diet with Exercise in Nonalcoholic Fatty Liver Disease

Our aım was to evaluate effects of metformin, rosiglitazone, and diet with exercise in nonalcoholic fatty liver disease. Forty-seven patients (mean age, 44±10 years; 17 female) whose ALT levels had been high for at least 6 months and with hepatosteatosis detected by liver biopsy and/or USG were enrolled in this study. Of these, 12 were treated with 850 mg/day metformin (group 1), 11 with 4 mg/day rosiglitazone (group 2), and 24 with diet and exercise (group 3) for 1 year. ALT normalization at months 6 and 12 was accepted as treatment response. Liver biopsy was performed in all patients in groups 1 and 2 before treatment and 12 patients (4 in group 1, 8 in group 2) after treatment; but in group 3 it was performed only in patients who approved this procedure (12 patients). Body mass index did not change in groups 1 and 2, but it decreased significantly in group 3 (30±3 to 28±2 kg/m²) at month 12. Treatment response rate was 33.3, 54.5, and 54.2% in groups 1, 2, and 3, respectively, at month 6. This rate was 22.2, 37.5, and 41.2 in groups 1, 2, and 3, respectively, at month 12. Rate of steatosis and stage of fibrosis did not change after treatment. Diet with exercise seems to be superior to metformin and rosiglitazone. Decreasing treatment response at month 12 compared to month 6 may be due to fluctuations of ALT levels. Treatment response should be evalulated histologically.     

Induction of a 72-kDa Heat Shock Protein and Cytoprotection Against Thioacetamide-Induced Liver Injury in Rats

Heat shock proteins are ubiquitous intracellularproteins induced by various physiological stress-relatedevents. A 72-kDa heat shock protein (HSP72) has beenreported to be an endogenous cytoprotectant in variety of cells in vitro . In order tostudy the cytoprotective function of HSP72 in the liver,the effect of preinduction of HSP72 in rat liver bysystemic hyperthermia on thioacetamide-induced hepatic injury was investigated in this study.Expression of HSP72 in the liver was investigated byimmunoblot and densitometric analysis. Rats wereinjected with thioacetamide (100 mg/kg, subcutaneously)with or without preinduction of HSP72 byhyperthermia. Serum AST and ALT concentrations weremeasured before and after thioacetamide injection inboth group. Histologic alteration of the liver wasevaluated also. Systemic hyperthermia (42.5°C, 20min) significantly induced HSP72 in the liver.Thioacetamide-induced hepatic injury was clearlyprevented by preinduction of HSP72 by hyperthermia.Prevention of hepatocyte damage was more clear in the areaaround central veins where HSP72 induction was apparent.Our findings might suggest that HSP72 has an importantfunction in the liver with respect to cytoprotection. These results might be important forunderstanding the mechanism of adaptivecytoprotection in the liver mediated by thefunction of heat shock proteins as molecularchaperons as reported in vitro.     

Changes in Microsomal Phospholipases and Arachidonic Acid in Experimental Alcoholic Liver Injury: Relationship to Cytochrome P-450 2E1 Induction and Conjugated Diene Formation

We evaluated the role of changes in microsomal phospholipases (A and C) and arachidonic acid in the intragastric rat feeding model. The experimental animals (male Wistar rats), divided into 4–5 rats/group, were fed the following diets: corn oil and ethanol and corn oil plus dextrose. One set of groups was killed after 2 weeks of feeding, and the second set was killed after 1 month. For each animal, microsomal analysis of cytochrome P-450 2E1 (CYP 2E1) and fatty acids was done. Fourteen animals had analyses of phospholipase C (PLC) and phospholipase A (PLA), and 10 animals had measurements of conjugated dienes. A significant correlation was obtained between the level of CYP 2E1 and the decrease in arachidonic acid (AA) from baseline levels ( r = 0.69, p < 0.01). The decrease in AA also correlated with the increase in conjugated dienes ( r = 0.70, p < 0.05). PLA and PLC activities were both significantly increased in the corn oil and ethanol groups. The activity of PLC correlated with the decline in AA ( r = 0.69, p < 0.01). The correlations noted between the decrease in microsomal AA and CYP 2E1 induction and conjugated diene formation suggest that these processes may be interlinked especially in regard to generation of lipid peroxides that may play a role in alcoholic liver injury.     

Correlation Between Adenosine Triphosphate Content and Apoptosis in Liver of Rats Treated With Alcohol

Background: Chronic alcohol consumption depresses adenosine triphosphate (ATP) synthesis and induces mitochondrial DNA (Mt-DNA) deletion. ATP content in cells may play a critical role in inducing cell death, apoptosis, or necrosis. However, it is unknown which type of cell death occurs in alcoholic liver disease. In this study, the deletions of hepatic Mt-DNA, hepatic ATP content, and the number of single-stranded DNA (ss-DNA) of hepatocytes in rats treated with ethanol were determined to elucidate the relationship among Mt-DNA deletion, ATP synthesis, and/or hepatic apoptosis.
Methods: Sixteen male Wistar rats were fed with a liquid diet containing 36% ethanol (E group) or liquid diet without ethanol (C group) for 5 weeks. Hepatic ATP content was measured and the deletions of Mt-DNA encoding complexes I, IV, and V were determined in fresh liver tissue, and ss-DNA was stained in paraffin sections.
Results: Fatty change was observed in the E group, but not in the C group. Hepatic ATP content in the E group was 0.44 μmol/g of liver, which was significantly lower than that in the C group (0.84 μmole/g of liver). However, no deletion of Mt-DNA encoding complexes I, IV, and V was detected in either the E or the C group. ss-DNA staining was clearly observed in the nuclei of hepatocytes in both groups. The number of ss-DNA-positive hepatocytes in the E group was 5.6 ± 1.8/10,000 hepatocytes, which was significantly less than that in the C group: 20.6 ± 4.8/10,000 hepatocytes. There was a positive correlation between hepatic ATP contents and the number of ss-DNA-positive cells.
Conclusions: The results suggest that mitochondrial function, at least in part ATP synthesis, was depressed before the damage of Mt-DNA by chronic ethanol consumption. Chronic ethanol consumption may not be responsible for the apoptosis of hepatocytes.     

Exercise training prevents beta-adrenergic hyperactivity-induced myocardial hypertrophy and lesions

BACKGROUND: Sustained beta-adrenoreceptor activation promotes cardiac hypertrophy and cellular injury. AIMS: To evaluate the cardioprotective effect of exercise on damage induced by beta-adrenergic hyperactivity. METHODS: Male Wistar rats were randomised into four groups (n=8 per group): sedentary non-treated control (C), sedentary treated with isoproterenol 0.3 mg/kg/day administered subcutaneously for 8 days (I), exercised non-treated (E) and exercised plus isoproterenol administered during the last eight days of exercise (IE). Exercised animals ran on a treadmill for 1 h daily 6 times a week for 13 weeks. RESULTS: Isoproterenol caused increases in left ventricle (LV) wet and dry weight/body weight ratio, LV water content and cardiomyocyte transverse diameter. Additionally, isoproterenol induced severe cellular lesions, necrosis, and apoptosis, increased collagen content and reduced capillary and fibre fractional areas. Notably, all of these abnormalities were completely prevented by exercise. CONCLUSION: Our data have demonstrated that complete cardioprotection is possible through exercise training; by preventing beta-adrenergic hyperactivity-induced cardiac hypertrophy and structural injury.     

Sarcopenia in Patients with Chronic Liver Disease: Can It Be Altered by Diet and Exercise?

Sarcopenia, a loss of muscle mass, is being increasingly recognized to have a deleterious effect on outcomes in patients with chronic liver disease. Factors related to diet and the inflammatory nature of chronic liver disease contribute to the occurrence of sarcopenia in these patients. Sarcopenia adversely influences quality of life, performance, morbidity, success of transplantation, and even mortality. Specific deficiencies in macronutrients (protein, polyunsaturated fatty acids) and micronutrients (vitamins C, D, and E, carotenoids, and selenium) have been linked to sarcopenia. Lessons learned from nutritional therapy in geriatric patient populations may provide strategies to manage sarcopenia in patients with liver disease. Combining diet modification and nutrient supplementation with an organized program of exercise may help ameliorate or even reverse the effects of sarcopenia on an already complex disease process.     

Bioenergetics in the aging Fischer 344 rat: effects of exercise and food restriction

The capacity for energy production was evaluated in male, Fischer 344 rats as they advanced from adulthood through senescence. At 10 months of age, the animals were divided into three groups: sedentary, fed ad libitum (S); exercised by treadmill running, fed ad libitum (E); and sedentary, caloric restricted by alternate day feeding (R). Activities of selected enzymes, ADP-stimulated respiration and levels of cytochromes, were determined in homogenates of liver and gastrocnemius muscle prepared from young controls (10-month old S) and 18-, 24-, and 30-month old animals. In liver, age-linked decrements were found in the activities of 3-hydroxyacyl-CoA dehydrogenase (S, E, and R) and citrate synthase (S), and in cytochrome c content (S and E), whereas substrate-catalysed oxidations were unaffected. In the gastrocnemius muscle (S, E, and R), respiration, activities of enzymes of the Krebs cycle and glycolysis, and cytochrome content were decreased after the age of 18 months. Oxidative capacity was increased in muscle through exercise (about 40%) and in liver by food restriction (about 20%). Body and soleus muscle mass declined similarly in all groups (about 14% from 30 to 18 months of age), whereas the loss of weight in the gastrocnemius muscle was much greater (34%). The data indicate that energy metabolism in the senescent animal is competent to meet its needs and age-related declines in energy metabolism are secondary to the aging process.     

Exercise at anaerobic threshold intensity and insulin secretion by isolated pancreatic islets of rats

To evaluate the effect of acute exercise and exercise training at the anaerobic threshold (AT) intensity on aerobic conditioning and insulin secretion by pancreatic islets, adult male Wistar rats were submitted to the lactate minimum test (LMT) for AT determination. Half of the animals were submitted to swimming exercise training (trained), 1 h/day, 5 days/week during 8 weeks, with an overload equivalent to the AT. The other half was kept sedentary (sedentary). At the end of the experimental period, the rats were submitted to an oral glucose tolerance test and to another LMT. Then, the animals were sacrificed at rest or immediately after 20 minutes of swimming exercise at the AT intensity for pancreatic islets isolation. At the end of the experiment mean workload (% bw) at AT was higher and blood lactate concentration (mmol/L) was lower in the trained than in the control group. Rats trained at the AT intensity showed no alteration in the areas under blood glucose and insulin during OGTT test. Islet insulin content of trained rats was higher than in the sedentary rats while islet glucose uptake did not differ among the groups. The static insulin secretion in response to the high glucose concentration (16.7 mM) of the sedentary group at rest was lower than the sedentary group submitted to the acute exercise and the inverse was observed in relation to the trained groups. Physical training at the AT intensity improved the aerobic condition and altered insulin secretory pattern by pancreatic islets.     

Effect of Treadmill Exercise and Ferula gummosa on Myocardial HSP72, Vascular Function,and Antioxidant Defenses in Spontaneously Hypertensive Rats

This study evaluates the effect of treadmill exercise and Ferula gummosa (FG) on heat shock protein (HSP72), biomarkers related to vascular function, and oxidant/antioxidant system in the heart tissue of spontaneously hypertensive rats treated with N(ω)-nitro-l–arginine-methyl ester (l–NAME). Fifty adult male Wistar rats are randomly classified into five groups: treadmill exercise, FG, combination of treadmill exercise + FG, l–NAME, and saline. Treadmill exercise was performed between 25 and 64 minutes at the speed of 15–22 m per minute for 8 weeks and five sessions a week. The FG will be fed through gavage with 90 mg/kg dosage. Hypertension was induced by l–NAME (10 mg/kg) for 8 weeks and six sessions a week. Administration of l–NAME for 8 weeks caused significant increase in HSP72, angiotensin-converting enzyme (ACE), and protein carbonyl (PC), and significant decrease in glutathione peroxidase (GPx) and nitric oxide (NO) level, when compared with the saline group. In contrast, both treadmill exercise and/or FG protocols, in particular, the combined protocol, led to the improvement in HSP72 and balance in oxidant/antioxidant process and inhibited vascular dysfunction, when compared with the l–NAME group. Moreover, no significant differences were detected in the HSP72 level between rats in the treadmill exercise and FG groups. These results provide a rationale for an inhibitory role and a cardioprotective effect of lifestyle related to the health in the attenuation of hypertension-induced cardiotoxicity.     

维生素C,E对氟中毒大鼠肝、肾、脑组织形态学变化的干预作用

目的 探讨过量氟对实验大鼠肝、肾、脑的损害及维生素C,E的影响.方法 将120只Wistar大鼠随机分为9组,经饮水投氟建立氟中毒动物模型,并灌胃补充维生素C,E,9个月后处死大鼠,利用光镜观察氟中毒大鼠肝、肾、脑的形态学变化以及维生素C,E干预的影响.结果 氟中毒各组大鼠肝、肾、脑出现明显的组织形态学改变.肝组织的变化最为明显,表现为肝细胞水肿和点状坏死及汇管区炎性细胞浸润.肾脏以肾小球毛细血管扩张和肾小管上皮细胞水肿及肾间质出血为主要改变.脑神经胶质细胞增殖、水肿及间质血管扩张伴出血和炎性细胞浸润.维生素C,E单独干预组肝、肾、脑组织因氟中毒而发生的形态学改变均较染氟组轻.维生素C,E联合干预组各组织的形态学变化均比单独干预组轻.结论 过量氟引起大鼠肝、肾、脑组织不同程度的损害,经维生素C,E干预对过量氟引起的大鼠各组织损害有明显的拮抗作用,其中联合干预效果较为明显,干预效果与干预剂量和氟中毒损害的靶器官有关.     

L-Buthionine (S,R) sulfoximine depletes hepatic glutathione but protects against ethanol-induced liver injury

BACKGROUND: L-Buthionine (S,R) sulfoximine (BSO) is an inhibitor of glutathione biosynthesis and has been used as an effective means of depleting glutathione from cells and tissues. Here we investigated whether treatment with BSO enhanced ethanol-induced liver injury in mice. METHODS: Female C57Bl/6 mice were pair fed with control and ethanol-containing liquid diets in which ethanol was 29.2% of total calories. During the final 7 days of pair feeding, groups of control-fed and ethanol-fed mice were given 0, 5 or 7.6 mM BSO in the liquid diets. RESULTS: Compared with controls, ethanol given alone decreased total liver glutathione. This effect was exacerbated in mice given ethanol with 7.6 mM BSO, causing a 72% decline in hepatic glutathione. While ethanol alone caused no decrease in mitochondrial glutathione, inclusion of 7.6 mM BSO caused a 2-fold decline compared with untreated controls. L-Buthionine (S,R) sulfoximine did not affect ethanol consumption, but serum ethanol levels in BSO-treated mice were nearly 6-fold lower than in mice given ethanol alone. The latter decline in serum ethanol was associated with a significant elevation in the specific activities of cytochrome P450 2E1 and alcohol dehydrogenase in livers of BSO-treated animals. Ethanol consumption caused a 3.5-fold elevation in serum alanine aminotransferase levels but the enzyme fell to control levels when BSO was included in the diet. L-Buthionine (S,R) sulfoximine administration also attenuated ethanol-induced steatosis, prevented the leakage of lysosomal cathepsins into the cytosol, and prevented the ethanol-elicited decline in proteasome activity. CONCLUSIONS: L-Buthionine (S,R) sulfoximine, administered with ethanol, significantly depleted hepatic glutathione, compared with controls. However, despite the decrease in hepatic antioxidant levels, liver injury by ethanol was alleviated, due, in part, to a BSO-elicited acceleration of ethanol metabolism.