Restraint stress induced changes in rat liver and serum metallothionein and in Zn metabolism

Summary 24 h of a psychogenic stress (restraint) caused a strong increase of liver metallothionein (MT) levels. 3 h of stress were sufficient to induce an increase in liver MT, measured 21 h later, but the increase was much lower than in continuously restrained rats. Stress induction of liver MT was not due to food deprivation, since rats deprived for 24 h showed lower MT levels than stressed ones. Zn on MT presented the same qualitative but not quantitative pattern of response as MT protein. Liver cytosolic Zn was increased by restraint in spite of their being no decrease in serum Zn. Any treatment altered serum MT. Liver and serum MT were not correlated. The present results demonstrate that basically psychogenic stresses increased liver but not serum MT levels. No positive evidence for a relationship between corticosterone secretion and MT induction was found.     

Metallothionein induction by cadmium and zinc in rat secretory organs

Summary Metallothionein (MT) levels were determined in four secretory organs of the rat following administration of zinc (Zn) and cadmium (Cd). The concentrations of MT in the lacrimal, parotid and adrenal glands of untreated rats were in the range of 2.2–4.9 g/g wet weight tissue while in the pancreas it was shown to be 15.2 g/g. Injection of zinc at total doses of 16, 32 and 80 mg/kg resulted in a 1.8-, 3.2- and 5.9-fold increase in lacrimal MT content, respectively, while a 10.2- and 13.1-fold elevation was observed following treatment with 4 and 8 mg/kg of Cd, respectively. Similar findings were found in the adrenal gland. The parotid MT was elevated 5.9 and 17 times following Zn treatment at doses of 16 and 80 mg/kg respectively, whereas 4 mg/kg of Cd increased MT 14.4 times in this gland. Pancreatic MT was elevated by 39- and 40-fold after injection of Zn at doses of 16 and 32 mg/kg respectively, whereas 4 and 8 mg/kg of Cd caused a 9.8- and 17.9-fold induction, respectively. These results may indicate that secretory organs participate in metabolism of heavy metals in the mammalian body.     

Metallothionein induction by cadmium and zinc in rat secretory organs

Metallothionein (MT) levels were determined in four secretory organs of the rat following administration of zinc (Zn) and cadmium (Cd). The concentrations of MT in the lacrimal, parotid and adrenal glands of untreated rats were in the range of 2.2-4.9 micrograms/g wet weight tissue while in the pancreas it was shown to be 15.2 micrograms/g. Injection of zinc at total doses of 16, 32 and 80 mg/kg resulted in a 1.8-, 3.2- and 5.9-fold increase in lacrimal MT content, respectively, while a 10.2- and 13.1-fold elevation was observed following treatment with 4 and 8 mg/kg of Cd, respectively. Similar findings were found in the adrenal gland. The parotid MT was elevated 5.9 and 17 times following Zn treatment at doses of 16 and 80 mg/kg respectively, whereas 4 mg/kg of Cd increased MT 14.4 times in this gland. Pancreatic MT was elevated by 39- and 40-fold after injection of Zn at doses of 16 and 32 mg/kg respectively, whereas 4 and 8 mg/kg of Cd caused a 9.8- and 17.9-fold induction, respectively. These results may indicate that secretory organs participate in metabolism of heavy metals in the mammalian body.     

Hypersensitivity to endotoxin hepatotoxicity in rats with inflammatory lesions

Summary The ratio of sinusoidal nonparenchymal cells to hepatocytes in rat liver was significantly increased following induction of inflammation, and decreased after subsequent exposure to endotoxin, particularly in the region around the terminal portal venules. Rats with inflammatory lesions were more sensitive to endotoxin hepatocytotoxicity than normal controls, as judged from the dose-dependent increase in activity of serum transaminases and from the extent of liver tissue injury. In addition, these animals, which were already in a state of depletion of hepatic glycogen, demonstrated marked hyperglycemia 24 h after endotoxin administration in small doses of less than 2 mg/kg.     

Hypersensitivity to endotoxin hepatotoxicity in rats with inflammatory lesions

The ratio of sinusoidal nonparenchymal cells to hepatocytes in rat liver was significantly increased following induction of inflammation, and decreased after subsequent exposure to endotoxin, particularly in the region around the terminal portal venules. Rats with inflammatory lesions were more sensitive to endotoxin hepatocytotoxicity than normal controls, as judged from the dose-dependent increase in activity of serum transaminases and from the extent of liver tissue injury. In addition, these animals, which were already in a state of depletion of hepatic glycogen, demonstrated marked hyperglycemia 24 h after endotoxin administration in small doses of less than 2 mg/kg.     

Effects of Freund's complete adjuvant on the dirunal rhythms of neuroendocrine processes and ornithine decarboxylase activity in various tissues of male rats

The aim of this study was to investigate the effects of Freund's complete adjuvant (FCA) on the diurnal rhythms of hormonal parameters in serum and ornithine decarboxylase (ODC) activity in various tissues of male rats. On days 1–2 after FCA, increase of ODC activity (used to evaluate the level of activation) was observed in the hypothalamus, pituitary gland, adrenal medulla, adrenal cortex, liver and lymphoid tissues, while the ODC activity in the kidney was reduced. This was accompanied by an increase in serum corticosterone. On days 3–4 after FCA, ODC activity remained elevated in the pituitary gland, liver and lymphoid tissues, while the ODC activity in the testes and panceas was reduced; kidney ODC activity returned to baseline. This was associated with increased serum levels of prolactin (Prl) and luteinizing hormone, but decreased growth hormone, testosterone and insulin. The increase in ODC activity in the thymus, as well as the reduced ODC activity in the testes and kidney, can be obtained with paraffin. Furthermore, bromocryptine microcapsules (CBLA) reduced the FCA-induced increase of ODC activity in the pituitary gland, liver and lymphoid tissues (days 3–4) but did not affect the changes in other tissues. The increase in ODC activity in the pituitary gland, liver and lymphoid tissues is specific for FCA. A role for Prl in the induction of ODC in liver and lymphoid tissues is suggested by the fact that CBLA suppresses this enhancement.     

Effects of chronic caffeine feeding on the activities of oxygen free radical defense enzymes in the growing rat heart and liver

The purpose of the present study was to determine the relationship between concentration of Zn, Cu and Fe, and the catalase, glutathione peroxidase and superoxide dismutase activities in the heart and liver of newborn rats whose dams were fed a diet supplemented with caffeine. Heart Zn levels of the 22- and 30-day-old rats of the caffeine group showed a decrease, whereas liver Zn levels showed an increase compared to the control. Cu levels in the liver at day 22 in the caffeine group were less than in the control. Cu- and Zn-containing superoxide dismutase activities showed an increase in the hearts of the caffeine group compared to the control. The activity of catalase and glutathion peroxidase showed no difference in the heart and liver between the groups. The present study suggests the possible involvement of superoxide dismutase enzyme in the impairment of heart formation as a result of chronic caffeine intake in the early growing period.     

参附动员内皮祖细胞改善肝移植大鼠缺血再灌注损伤

目的 观察参附注射液对发生肝移植缺血再灌注损伤(IRI)的大鼠外周血中内源性内皮祖细胞(EPCs)的作用以及此作用对其肝脏功能的影响.方法 100只雌性SD大鼠随机分为3组:原位肝移植(0LT)+参附(SF)组,OLT对照组,假手术组.3组均于术后第1、4、7天取血液标本流式细胞术检测外周血内皮祖细胞数量及生化分析仪检测肝功能,观察胆汁分泌量,并取肝组织标本进行HE染色形态学观察肝脏损伤.结果 OLT+ SF组外周血中的EPCs在术后1天开始增加,第4天达到高峰并持续至第7天;并且在3个时间点上,OLT+ SF组的外周血EPCs数量较其它两组明显增加,具有统计学意义(p ＜0.01);OLT+ SF组在用药后IRI有所改善,较对照组有统计学差异(p＜0.05).结论 参附注射液能显著动员大鼠骨髓中的内源性EPCs进入外周血,修复损伤的肝血窦,改善微循环,进而改善肝移植术后的缺血再灌注损伤.     

Liver steatogenic power of high doses of rifampicin in rats]

The possible induction of fatty liver by Rifampicin has been investigated by oral administration of two different doses (200 and 400 mg/kg/24 h) of this antibiotic for a period of 8 days to male and female Rats. The results obtained are more constant and more coherent in male than in female. It is the 400 mg/kg/24 h dose which is more effective, leading to an increase of lipids, triglycerides and cholesterol in the liver and a decrease of serum triglycerides. A dose-effect relationship may exist. These preliminary data lead us to believe that Rifampicin may inhibit the synthesis of the protein moiety of lipoproteins, such as alpha-Amanitin, which is also a RNA-polymerase inhibitor.     

Hypolipidemic effects of garlic oil in rats fed ethanol and a high lipid diet

Summary Feeding of ethanol and a high fat-high cholesterol diet to rats markedly increased the total lipids in the liver, and cholesterol and triglyceride levels in the serum, liver and kidneys. However, when ethanol mixed with 0.5% garlic oil was fed to animals maintained on the high fat-high cholesterol diet, these lipid levels were significantly reduced to levels near to those seen in untreated control rats. Garlic oil did not reduce the serum albumin or the total proteins of liver, kidneys or serum when fed along with ethanol. Probably the garlic oil enhances the catabolism of dietary cholesterol and fatty acids.The authors acknowledge with thanks the financial assistance of the University of Maiduguri for carrying out this project.     

Pseudocholinesterase in obesity: Hypercaloric diet induced changes in experimental obese mice

Summary Pseudocholinesterase activity is significantly higher in liver and serum, but lower in adipose tissue of genetically obese, diabetic and gold thioglucose treated mice. Similar enzyme changes were also observed in lean mice on a high carbohydrate diet. A marked reduction (40%) in PChE activity occurred in the liver of genetically diabetic mice when starved for 24 h. These observations suggest that pseudocholinesterase induction in the liver and repression in the adipose tissue is affected by excessive calorie intake in obesity. This provides a model to study the biological function of PChE in health and disease.Acknowledgments. We thank Dr Charles A. Janeway Child Health Centre and Faculty of Medicine, Memorial University of Newfoundland for financial support.     

Zinc,copper and manganese levels in various tissues following fluoride administration

Summary Distribution of zinc, copper and manganese has been studied in liver, kidney and bone of rats subjected for 10 months to varied fluoride concentrations in drinking-water. In the liver a significant fall in the levels of Mn, Cu and Zn was registered. In the kidney, the Mn level fell whereas the zinc level increased. In the bone, the copper content fell, whereas the manganese content increased.     

Acetyl-L-carnitine treatment stimulates oxygen consumption and biosynthetic function in perfused liver of young and old rats

The effect of treatment with acetyl-L-carnitine on hepatic mitochondrial respiration and biosynthetic function in perfused liver from young (90 days) and old (22-24 months) rats was studied. Rats were given a 1.5% (w/v) solution of acetyl-L-carnitine in their drinking water for 1 month and oxygen consumption together with the rate of gluconeogenesis, urea synthesis, and ketogenesis with and without added substrates were measured in perfused liver. Mitochondrial oxygen consumption was also assessed in liver homogenate and isolated mitochondria to determine the maximal capacity for oxidative phosphorylation. Acetyl-L-carnitine treatment almost completely restored the age-dependent decline in oxygen consumption, gluconeogenesis, urea synthesis, and ketogenesis found in perfused liver of old rats to the levels found in young rats. In addition, acetyl-L-carnitine treatment increased oxygen consumption and biosynthetic function in perfused liver from young rats. After acetyl-L-carnitine treatment, we found detectable 3-oxoacyl-CoA-transferase activity associated with a consumption of ketone bodies in young and old rats. Finally, oxygen consumption measured in homogenate and isolated mitochondria did not change with age and acetyl-L-carnitine treatment. Our results show that in perfused liver, acetyl-L-carnitine treatment slows the age-associated decline in mitochondrial respiration and biosynthetic function. In addition, treatment of young rats with acetyl-L-carnitine has a stimulating effect on liver metabolism, probably through an increase in ATP production. Received 25 October 2000; received after revision 14 December 2000; accepted 11 January 2001     

Development and hormonal control of thioredoxin and the thioredoxin-reductase system in the rat liver during the perinatal period

The development and hormonal regulation of thioredoxin and of the thioredoxin-reductase system were investigated during the perinatal period in rat liver. An immunological procedure was developed in order to quantify thioredoxin in fetal and neonatal hepatocytes. Both immunoreactive thioredoxin and thioredoxin-reductase activity appeared on day 16.5 of pregnancy. The level of immunoreactive thioredoxin increased during the late fetal period, and its level was the same 24 h after birth. Moreover, its development was not subjected to hormonal regulation by corticosteroids and glucagon. In contrast, thioredoxin-reductase activity increased 3 times during the late fetal period and presented a marked increase 24 h after birth. In the absence of glucocorticoids there was no increase in the level of thioredoxin reductase, while administration of hydrocortisone acetate and glucagon to fetuses prematurely evoked its activity. This study suggests that if thioredoxin acts physiologically, this activity is related to the state of reduction of the molecule rather than to the total concentration in the liver.     

Development and hormonal control of thioredoxin and the thioredoxin-reductase system in the rat liver during the perinatal period

Summary The development and hormonal regulation of thioredoxin and of the thioredoxin-reductase system were investigated during the perinatal period in rat liver. An immunological procedure was developed in order to quantify thioredoxin in fetal and neonatal hepatocytes. Both immunoreactive thioredoxin and thioredoxin-reductase activity appeared on day 16.5 of pregnancy. The level of immunoreactive thioredoxin increased during the late fetal period, and its level was the same 24 h after birth. Moreover, its development was not subjected to hormonal regulation by corticosteroids and glucagon. In contrast, thioredoxin-reductase activity increased 3 times during the late fetal period and presented a marked increase 24 h after birth. In the absence of glucocorticoids there was no increase in the level of thioredoxin reductase, while administration of hydrocortisone acetate and glucagon to fetuses prematurely evoked its activity. This study suggests that if thioredoxin acts physiologically, this activity is related to the state of reduction of the molecule rather than to the total concentration in the liver.     

Mitochondrial respiratory function and antioxidant capacity in normal and cirrhotic livers following partial hepatectomy

For many liver malignancies, major hepatectomy is the usual therapy. Although a normal liver has a tremendous capacity for regeneration, liver hepatectomy in humans is usually carried out on a diseased liver and, in such cases, liver regeneration takes place in a cirrhotic remnant. Mitochondrial function in cirrhotic livers shows a variety of changes compared to control livers. This study investigated how mitochondrial respiratory function and antioxidant capacity change following partial hepatectomy of cirrhotic livers, because liver regeneration requires greater energy demands and control of oxidative stress. Cirrhosis was induced in male Wistar-Furth rats by administration of thioacetamide. NADH-cytochrome c reductase activity, mitochondrial glutathione peroxidase activity and mitochondrial GSH levels were all significantly lowered in cirrhotic livers and in the cirrhotic remnants up to 72 h after 70% hepatectomy when compared to the corresponding controls. Lower respiratory control ratios with succinate as substrate were also observed from 6 to 48 h post-hepatectomy. At 24 h post-hepatectomy, higher levels of lipid peroxidation were observed. We conclude that, compared to the controls, cirrhotic livers have diminished oxidative phosphorylation capabilities due to changes in NADH and FADH₂-linked respiration as well as impaired antioxidant defenses following partial hepatectomy. Both of these factors, if critical, could then impede liver regeneration.Received 15 September 2003; received after revision 26 October 2003; accepted 19 November 2003     

Differential influences of various arsenic compounds on glutathione redox status and antioxidative enzymes in porcine endothelial cells

The cellular response and detoxification mechanisms in porcine endothelial cells (PAECs) to arsenic trioxide (As2O3), sodium arsenite (NaAsO2) and sodium arsenate (Na2HAsO4) were investigated. NaAsO2 at 20 microM for 72 h increased Cu/Zn superoxide dismutase activity resulting in elevated intracellular hydrogen peroxide levels, but As2O3 and Na2HAsO4 did not. Trivalent arsenic compounds increased intracellular oxidized glutathione (GSSG) and total glutathione (GSH) and cellular glutathione peroxidase (cGPX) and glutathione S-transferase (GST) activity, but not glutathione reductase activity. The increased cGPX activity resulted in an elevated cellular GSSG content. Na2HAsO4 increased the cellular GSSG level at 72 h compared to controls. These results imply that the increased GSH content responding to the oxidative stress by trivalent arsenic compounds may be mainly related to the regulation of GSH turnover. The increased GST activity implies that the elevated intracellular GSH level responding to the oxidative stress may be used to conjugate arsenic in PAECs and facilitate arsenic efflux.     

Effect of consumption of green and black tea on the level of various enzymes in rats

Drinking of both green and black tea as the only liquid ingested resulted in significant decreases in the activity of transketolase in whole blood of rats both before and after the in vitro addition of thiamin diphosphate. Liver transketolase activity was decreased only by green tea. Mucosal transketolase activity was not affected by either type of tea. The activity of lactate dehydrogenase (LDH) was not affected by either type of tea, while whole blood LDH was decreased by both green and black tea. Neither tea had any affect on mucosal alkaline phosphatase, but thiamin diphosphatase activity was decreased by both teas. An increase in liver total thiamin resulted from the drinking of both types of tea.     

Postischemic ATP levels predict hepatic function 24 hours following ischemia in the rat

Hepatic function was assessed by the aminopyrine breath test (ABT) in male Sprague Dawley rats 24 h after partial hepatic ischemia. ABT decreased progressively to 26.3 (p less than 0.05) and 19.7% of dose (p less than 0.05) after 90 and 120 min of ischemia, respectively. ABT at 24 h after injury was correlated to the concentration of ATP in the ischemic lobes 1 h after the onset of reperfusion (r2 = 0.971) but not to ALT activity in plasma at 1 h (r2 = 0.391). We conclude that postischemic ATP levels are a better index of subsequent hepatic function than ALT.