Oxygen Consumption Of Liver Slices Research Articles

Modulation of methylmercury uptake by methionine: Prevention of mitochondrial dysfunction in rat liver slices by a mimicry mechanism

Methylmercury (MeHg) is an ubiquitous environmental pollutant which is transported into the mammalian cells when present as the methylmercury-cysteine conjugate (MeHg–Cys). With special emphasis on hepatic cells, due to their particular propensity to accumulate an appreciable amount of Hg after exposure to MeHg, this study was performed to evaluate the effects of methionine (Met) on Hg uptake, reactive species (RS) formation, oxygen consumption and mitochondrial function/cellular viability in both liver slices and mitochondria isolated from these slices, after exposure to MeHg or the MeHg–Cys complex. The liver slices were pre-treated with Met (250μM) 15min before being exposed to MeHg (25μM) or MeHg–Cys (25μM each) for 30min at 37°C. The treatment with MeHg caused a significant increase in the Hg concentration in both liver slices and mitochondria isolated from liver slices. Moreover, the Hg uptake was higher in the group exposed to the MeHg–Cys complex. In the DCF (dichlorofluorescein) assay, the exposure to MeHg and MeHg–Cys produced a significant increase in DFC reactive species (DFC-RS) formation only in the mitochondria isolated from liver slices. As observed with Hg uptake, DFC-RS levels were significantly higher in the mitochondria treated with the MeHg–Cys complex compared to MeHg alone. MeHg exposure also caused a marked decrease in the oxygen consumption of liver slices when compared to the control group, and this effect was more pronounced in the liver slices treated with the MeHg–Cys complex. Similarly, the loss of mitochondrial activity/cell viability was greater in liver slices exposed to the MeHg–Cys complex when compared to slices treated only with MeHg. In all studied parameters, Met pre-treatment was effective in preventing the MeHg- and/or MeHg–Cys-induced toxicity in both liver slices and mitochondria. Part of the protection afforded by Met against MeHg may be related to a direct interaction with MeHg or to the competition of Met with the complex formed between MeHg and endogenous cysteine. In summary, our results show that Met pre-treatment produces pronounced protection against the toxic effects induced by MeHg and/or the MeHg–Cys complex on mitochondrial function and cell viability. Consequently, this amino acid offers considerable promise as a potential agent for treating acute MeHg exposure.

Estimated hepatic oxygen consumption in patients with chronic liver diseases as assessed by organ reflectance spectrophotometry.

We investigated the estimated hepatic oxygen consumption by reflectance spectrophotometry during peritoneoscopy and the rate of in vitro oxygen consumption of liver slices obtained by liver biopsy using the oxygen electrode apparatus in patients with chronic liver diseases. The estimated hepatic oxygen consumption decreased concomitantly with the decrease in blood supply, expressed as the regional hepatic blood hemoglobin concentration, and it was significantly decreased in cirrhosis compared to chronic hepatitis. The estimated hepatic oxygen consumption also was significantly correlated with the serum albumin level, 15-min retention rate of indocyanine green, and prothrombin time. There was no correlation between the estimated hepatic oxygen consumption calculated from the reflectance spectra and the rate of in vitro oxygen consumption measured by the oxygen electrode apparatus. Most cirrhotic liver slices had a respiratory rate comparable to that in chronic hepatitis. Thus, it is concluded that the reduction of estimated hepatic oxygen consumption in cirrhosis of the liver is mainly due to the reduction of oxygen supply secondary to the decrease of hepatic blood flow.

Glucose tolerance and respiratory activities of human liver biopsies: their interdependence.

To determine a possible relation of hepatic oxidative activity to glucose metabolism, the rates of oxygen consumption of liver slices from patients with chronic liver diseases were polarographically measured. The livers from patients with chronic (persistent and aggressive) hepatitis and with normal glucose tolerance showed almost the same respiratory activity as those from patients with normal livers and normal glucose tolerance, whereas the livers from patients with chronic hepatitis and with diabetic glucose tolerance (ie, diabetes mellitus secondary to chronic hepatitis) showed only a half the normal level. The decreased rate of respiration was also observed in liver slices from cirrhotics with glucose intolerance. The decrease in respiration was found in patients with normal or hyperinsulinemia as well as hypoinsulinemia responding to oral glucose load. No liver tests so far examined, except the oral glucose tolerance test, correlated with hepatic respiratory activity. It is concluded that in patients with chronic liver diseases the defect of liver respiration has a close relation to the glucose metabolism and is not necessarily associated with histological change of the liver.

Thermal acclimation in selected tissues of the leopard frog Rana pipiens

1. 1. Significant correlations were found to exist in Rana pipiens between the in vitro metabolism of specific tissue and variables such as sex, season, photoperiod and length of acclimation, which necessitated the evaluation of temperature effects on tissue metabolism by using these factors as covariates. 2. 2. Adjusted mean oxygen consumption values for cardiac muscle indicated a clockwise rotation of the rate-temperature curve for the 5°C acclimation group while Q 10 values for this tissue demonstrated little metabolic dependence on temperature between 5 and 13°C. 3. 3. Skeletal muscle metabolism increased significantly ( P < 0.001) as temperatures of determination increased, but the Q 10 values were lower than would be predicted from a temperature-dependent system. 4. 4. Oxygen consumption of liver slices was highly temperature dependent with Q 10 values approximating 2.00. 5. 5. The rate-temperature curve for liver from the 5°C acclimation group displayed translation above the curve of the 20°C group while translation between these curves was in the opposite direction for skeletal muscle.

Further studies concerning the effects of clofibrate on respiration and oxidative phosphorylation of rat liver mitochondria

Clofibrate, administered in vitro, inhibited rat liver mitochondrial respiration at two sites within the respiratory chain. One site was between the interaction of NADH with NADH dehydrogenase and the point at which electrons from succinate oxidation enter the electron transport chain; another, less sensitive site, was between the interaction of succinate with succinate dehydrogenase and cytochrome c. In addition to these specific sites, clofibrate inhibited respiration by causing a depletion of pyridine nucleotides that was accompanied or followed by large-amplitude, non-energy-linked swelling. Clofibrate uncoupled oxidative phosphorylation at coupling sites II and III but not at site I. The concentrations required to cause loss of pyridine nucleotides were lower than those required to inhibit at the specific sites. p-Chlorophenoxyisobutyrate (CPIB) also inhibited succinate and β-hydroxybutyrate-linked respiration, and uncoupled oxidative phosphorylation, but at much higher concentrations (50 per cent inhibition of β-hydroxybutyrate oxidation at about 3·7 μmoles/mg of protein) than were required of clofibrate (50 per cent inhibition of β-hydroxybutyrate oxidation at about 0·17 μmole/mg of protein). Clofibrate administration to rats (100 and 300 mg/kg p.o. daily for 1 week) lowered serum lipid levels and increased the liver size, the amount of mitochondrial protein/g of liver, and the oxygen consumption of liver slices. However, mitochondria, isolated from livers of the treated rats, respired normally. A single administration of clofibrate (100 or 300 mg/kg, p.o.) did not affect liver slice respiration.

Ethanol metabolism in rats treated with ethyl-α-p-chlorophenoxyiso-butyrate (Clofibrate)

Clofibrate treatment (60 mg/day/100 g body wt im. for nine days) increased the liver to body weight ratio of the rats by 71 %. The activity of mitochondrial α-glycerophosphate dehydrogenase in the liver of clofibrate-treated rats was five times greater than in normal rat liver. The amounts of cytochrome a and mitochondrial protein per gram of liver wet weight were not changed. Clofibrate treatment increased the oxygen consumption of liver slices by 16 %. Ethanol increased the lactate/pyruvate ratio (an index of the redox state in the cytosolic compartment of the liver cell) in perfused normal livers and only slightly in the livers from clofibrate-treated rats. This effect of clofibrate is similar to that of thyroxine and seems to be due to enzyme induction, as diethylaminoclofibrate hydrochloride added in vitro did not prevent ethanol-induced increase in hepatic lactate/pyruvate ratio. Clofibrate treatment in rats significantly increased the disappearance rate of ethanol. The activity of hepatic alcohol dehydrogenase per gram of liver wet weight of per milligram of soluble protein was not changed by clofibrate treatment.

Influence of ethanol and butyraldoxime on liver metabolism

n-Butyraldoxime at a concentration of 10 −5 M inhibited the oxidation rate of ethanol by 71 per cent in rat liver slices. The inhibition was competitive with respect to ethanol, with an apparent inhibition constant of 3 × 10 −7 M. Butyraldoxime did not cause a rise in the acetaldehyde level of the intact rat liver during ethanol oxidation. No influence on the oxygen consumption of liver slices was observed. At a concentration of 10 −7 M the oxime counteracted the inhibiting effect of ethanol on the carbon dioxide production of liver slices and normalized the disturbances in the redox state of the liver cytosol. The unpleasant effects caused by butyraldoxime during ethanol metabolism seem not to be produced by disturbances of liver metabolism.

Relationship between daily rhythm in oxygen consumption of rat liver tissue and light-dark cycle

Oxygen consumption of liver slices from male Wistar rats was determined three times a day, morning, early afternoon and evening, by means of the Warburg manometric method.Under the lighting regimen of LD 12:12, light from 7:00 to 19:00, there was observed a circadian rhythm, with a trough at the onset of light and a peak just prior to the onset of darkness. After the inversion of the lighting regimen, i.e. light from 19:00 to 7:00, the phase of Qo2 and Qo2 (N) shifted gradually and reached eventually to 180° reversal by four weeks after the inversion of lighting.Our results suggest that there exists a endogenous periodicity in oxygen consumption of the liver tissue, which is entrained to a light-dark cycle as Zeitgeber and consequently appears as a circadian rhythm.

Influence of light-darkness change on O2 metabolism in rat liver

Similar diurnal periodicity in oxygen consumption of liver slices in Wistar rats was observed as that previously found in Sprague-Dawley rats. The rate of oxygen consumption was low in the morning and high in the evening. After inversion of lighting regimes, the phase shifted and reached the reversal curve in about 30 days. On the basis of these findings, it is estimated that diurnal periodicity in oxygen consumption of liver slices is influenced by alteration of the periods of light and darkness. Liver glycogen rhythm showed a reversed correlation to that of oxygen consumption in both lighting regimes.

EFFECTS OF VASOPRESSIN ON THE PLASMA CONCENTRATION OF FREE FATTY ACIDS AND IN VITRO OXYGEN CONSUMPTION OF TISSUES OF THE RAT

1. Effects of synthetic lysine vasopressin on the plasma concentration of FFA and in vitro oxygen consumption of tissues were studied in the rat.2. The plasma FFA concentration decreased significantly following the injection of vasopressin, while the effect of oxytocin was less marked. Pre-treatment with vasopressin caused a significant suppression on norepinephrine, effect in increasing the plasma FFA concentration.3. In vitro oxygen consumption of liver slices and hemidiaphragms was related to the medium concentration of palmitate.4. In vitro release of FFA by epididymal fat pads was not affected by the addition of vasopressin. FFA releasing effect of norepinephrine was not influenced by the presence of vasopressin.5. In vitro oxygen consumption of brown adipose tissue, liver and diaphragm was significantly reduced by the addition of vasopressin into the incubation medium, while that of white adipose tissue was not affected by vasopressin.

Biochemical Effects of Internal Irradiation

The studies reported here are concerned with the effect of internally administered radioactive sodium phosphate-P32 on the over-all metabolism of the rat liver, as reflected in changes in oxygen consumption and anaerobic glycolysis. The activities of several enzymes involved in these metabolic pathways have also been determined in the irradiated animals. In spite of the fact that the liver is generally regarded to be a radioresistant tissue, when radiation damage is measured in terms of observed histological changes, the metabolism of the livers of the irradiated animals has been examined because Perkinson and Ingols (3), using gallium citrate-Ga72, and Barron (4), using plutonium nitrate, have shown that the oxygen consumption of liver slices was significantly inhibited by the internal administration of radioisotopes. EXPERIMENTAL PROCEDURE

Oxygen consumption of liver slices from animals in shock.

ArticleOxygen Consumption of Liver Slices From Animals in ShockSherburne F. Cook, David Jensen, and Frank E. South JR.Sherburne F. CookFrom the Department of Physiology, School of Medicine, and Office of Naval Research, University of California, Berkeley, California, David JensenFrom the Department of Physiology, School of Medicine, and Office of Naval Research, University of California, Berkeley, California, and Frank E. South JR.From the Department of Physiology, School of Medicine, and Office of Naval Research, University of California, Berkeley, CaliforniaPublished Online:01 May 1953https://doi.org/10.1152/ajplegacy.1953.173.2.253MoreSectionsPDF (1 MB)Download PDF ToolsExport citationAdd to favoritesGet permissionsTrack citations ShareShare onFacebookTwitterLinkedInWeChat Previous Back to Top Next Download PDF FiguresReferencesRelatedInformation More from this issue > Volume 173Issue 2May 1953Pages 253-258 Copyright & PermissionsCopyright © 1953 by American Physiological Societyhttps://doi.org/10.1152/ajplegacy.1953.173.2.253PubMed13065436History Received 20 January 1953 Published online 1 May 1953 Published in print 1 May 1953 Metrics

Osmoregulation in surviving slices from the livers of adult rats.

The oxygen consumption of liver slices from adult rats was not significantly affected by the concentration of the medium when this lay between 0⋅20 and 0⋅45 osM/1. Alterations outside this range in either direction reduced the uptake of oxygen. Slices respiring at 38⋅5°C in solutions varying from 0⋅10 to 0⋅58 osm/1. always contained less water than slices in similar solutions at temperatures between 1 and 3°C. This difference was most noticeable with concentrations which did not inhibit respiration. When the oxygen uptake of slices in 0⋅30 osM media a t 38⋅5°C was inhibited by cyanide, the water content of the slices increased. Oxygen consumption increased and water content decreased again when cyanide was removed from the media. Small concentrations of 2, 4-dinitrophenol increased and larger concentrations reduced the uptake of oxygen, but both increased the amount of water in the tissue. The results suggest that the intracellular fluids are hypertonic, and that respiration governs the water balance of the tissue because some of the energy which it releases is used for active transport of water out of the cells through the mediation of compounds containing high-energy phosphate bonds. It is suggested that cloudy swelling results from a disturbance of the active transport of water.

Increased oxygen consumption, and succin-oxidase activity of liver tissue after exposure of rats to cold.

WHEN intact rats are exposed to a cold environment their consumption of oxygen increases greatly. Much of the increase may be accounted for by increased muscular activity, and direct evidence for this has been obtained. There is considerable evidence of an indirect nature which suggests that increased metabolism of non-muscular tissues may account for part of the increase. However, a direct demonstration of increased metabolic activity in visceral tissues has not yet been made. In an attempt to obtain such direct evidence, measurements of the oxygen consumption of liver slices, and of the succinoxidase activity of liver tissue homogenates, prepared from animals “acclimatized” to cold, were compared with those of normal rats.

The Effect of Pamaquin on the Oxygen Consumption of Liver Slices

The Effect of Pamaquin on the Oxygen Consumption of Liver Slices

TRITURUS TOXIN : CHEMICAL NATURE AND EFFECTS ON TISSUE RESPIRATION AND GLYCOLYSIS

The most active toxin preparation obtained had a potency of 64,000 mouse units (m.u.) per gram of organic material. Most of the nitrogen in this preparation was probably contained in inactive amino-acids, and the activity as calculated on the basis of the remaining nitrogenous material was between 1 and 2 million m.u. per gram.The effect of the toxin on respiration and glycolysis in certain organs of the rat was investigated. Oxygen consumption of liver slices appeared to be slightly and temporarily increased in the presence of 85 m.u. of toxin per ml. Similar effects were observed on the respiration of kidney and brain slices with a toxin concentration of 850 m.u. per ml. However, control studies with inactivated toxin makes it questionable whether these changes were attributable to the toxin per se.Anaerobic glycolysis in rat brain slices was progressively inhibited with higher concentrations of the toxin preparation. However, this effect was obtained only with concentrations far higher than those requi...

Respiration of Isolated Liver and Kidney Tissues from Adrenalectomized Rats

After adrenalectomy the basal metabolism of rats is depressed. It is possible that the depression is the result of metabolic disturbance in certain special organs or tissues rather than a general metabolic weakness. The oxygen consumption of brain tissue is not influenced by removal of the adrenal cortex, nor is that of skeletal muscle. The hepatic and renal malfunction resulting after ad-renalectomy suggests that energy reactions in these tissues may be altered. The rate of oxygen consumption of liver and kidney slices from rats showing marked symptoms of insufficiency (about 9 days after operation) is significantly depressed. The mean values together with the standard error of the mean are shown in Table I. The tissues were studied in Ringer's solution with phosphate buffer at pH 7.3 with no added substrate. The depression is not due to the starvation resulting from the marked anorexia which is present since a group of starved normal rats showed values very similar to those of the well-fed normals. The rate of oxygen consumption of liver slices from normal rats is considerably increased when pyruvic acid and succinic acid are added to the medium, indicating an active oxidation of these metabolites. It is now recognized that these substances are important intermediary metabolites in carbohydrate oxidation. The data presented in Table II show that after adrenalectomy the rate of oxidation of these substances is slower. Pyruvate oxidation is influenced to a greater extent than that of succinic acid (40% depression with pyruvate as compared with 30% in the case of succinate). The effect of adding dextrose to the medium is the same after adrenalectomy as before. It is concluded that oxidative systems are impaired by a deficiency of the adrenal cortex hormones, but the weakening appears to be general in nature rather than restricted to some one component of the oxidation chain.