PubMed Health⌕ Search

Biomedical subjects

R R Cardell

Publications and source records attributed to R R Cardell.

At least 37 records · Page 2Linked to original sources
PubMed1985

SERGE, the subcellular site of initial hepatic glycogen deposition in the rat: a radioautographic and cytochemical study.

Hormonal control of hepatic glycogen and blood glucose levels is one of the major homeostatic mechanisms in mammals: glycogen is synthesized when portal glucose concentration is sufficiently elevated and degraded when glucose levels are low. We have studied initial events of hepatic glycogen synthesis by injecting the synthetic glucocorticoid dexamethasone (DEX) into adrenalectomized rats fasted overnight. Hepatic glycogen levels are very low in adrenalectomized rats, and DEX causes rapid deposition of the complex carbohydrate. Investigation of the process of glycogen deposition was performed by light and electron microscopic (EM) radioautography using [3H]galactose as a glycogen precursor. Rats injected with DEX for 2-3 h and [3H]galactose one hour before being killed displayed an increasing number of intensely labeled hepatocytes. EM radioautography revealed silver grains over small (+/- 1 micron) ovoid or round areas of the cytosome that were rich in smooth endoplasmic reticulum (SER) and contained a high concentration of small dense particles. These distinct areas or foci of SER and presumptive glycogen (SERGE) were most numerous during initial periods of glycogen synthesis. After longer exposure to DEX (4-5 h) more typical deposits of cytoplasmic glycogen were evident in the SERGE regions. Several criteria indicated that the SERGE foci contained glycogen or presumptive glycogen: resemblance of the largest dense particles to beta-glycogen particles in EM; association of 3H-carbohydrate with the foci; removal of particles and label with alpha-amylase; and positive reaction with periodic acid-chromic acid-silver methenamine. The concentration of SER in the small foci and the association of newly formed glycogen particles with elements of SER suggest a role for this organelle in the initial synthesis of glycogen.

Animals↗
PubMed1984

Effects of compound 48/80 on hepatic glycogen and glucose-6-phosphatase early in the diurnal cycle of the rat.

The amount and distribution of glycogen as well as the activity of glucose-6-phosphatase (G-6-Pase) in the livers of rats were analyzed by biochemical and/or histochemical techniques. During the first 5 hr of the light cycle, livers of rats were sampled prior to and 30 min following an injection of compound 48/80 or Ringer's solution. Glycogen decreased significantly in response to sampling; however, treatment with compound 48/80 provoked an additional significant decrease in hepatic glycogen. These differences occurred irrespective of the time during the 5 hr that this was studied. The livers of the majority of the rats treated with compound 48/80 displayed a periportal distribution of glycogen, while those treated with Ringer's showed a more uniform pattern. Hepatic G-6-Pase activity was unchanged in either the Ringer's or compound 48/80 treated rats. These results indicated that (1) the significant glycogenolytic response occurs independently of the amount of glycogen present, (2) G-6-Pase activity is not affected within 30 min following the stimulation of glycogenolysis, (3) variation in glycogen patterns during depletion depends on the nature of the stimulus and/or degree of response, and (4) the amount of glycogen available for release is limited.

Animals↗
PubMed1984

Lobular and cellular patterns of early hepatic glycogen deposition in the rat as observed by light and electron microscopic radioautography after injection of 3H-galactose.

Very low hepatic glycogen levels are achieved by overnight fasting of adrenalectomized (ADX) rats. Subsequent injection of dexamethasone (DEX), a synthetic glucocorticoid, stimulates marked increases in glycogen synthesis. Using this system and injecting 3H-galactose as a glycogen precursor 1 hr prior to sacrifice, the intralobular and intracellular patterns of labeled glycogen deposition were studied by light (LM) and electron (EM) microscopic radioautography. LM radioautography revealed that 1 hr after DEX treatment, labeling patterns for both periportal and centrilobular hepatocytes resembled those in rats with no DEX treatment: 18% of the hepatocytes were unlabeled, and 82% showed light labeling. Two hours after treatment with DEX, 14% of the hepatocytes remained unlabeled, and 78% were lightly labeled; however, 8% of the cells, located randomly throughout the lobule, were intensely labeled. An increased number of heavily labeled cells (26%) appeared 3 hr after DEX treatment; and by 5 hr 91% of the hepatocytes were intensely labeled. Label over the periportal cells at this time was aggregated, whereas centrilobular cells displayed dispersed label. EM radioautographs showed that 2 to 3 hr after DEX injection initial labeling of hepatocytes, regardless of their intralobular location, occurred over foci of smooth endoplasmic reticulum (SER) and small electron-dense particles of presumptive glycogen, and in areas of SER and distinct glycogen particles. After 5 hrs of treatment with DEX, the intracellular distribution of label reflected the glycogen patterns characteristic of periportal or centrilobular regions.

Animals↗
PubMed1984

The effects of insulin replacement and withdrawal on hepatic ultrastructure and biochemistry.

This study examines the early hepatic biochemical and ultrastructural responses to insulin replacement in streptozotocin-diabetic rats and insulin withdrawal from insulin-maintained diabetic rats. Insulin administration rapidly lowered plasma glucose and the elevated glucose-6-phosphatase (G-6-Pase) specific activity of the diabetic rats. However, hepatic glycogen did not increase until after 3 hr of insulin treatment. Hepatic ultrastructure responded to insulin replacement after the decline in glucose and G-6-Pase. This was seen in periportal hepatocytes as a reduction in the close association between smooth endoplasmic reticulum (SER) and glycogen particles in the diabetic animals. The treated rats showed hepatic SER restricted to the periphery of glycogen masses, as is characteristic of these cells from normal rats, in many cells by 6 hr and all cells by 18 hr. Insulin withdrawal from insulin-treated diabetic rats elicited nearly a total reversal of the above events. Plasma insulin declined to a value half that of the normal rats by 6 hr after withdrawal; concurrently, plasma glucose rose sharply to hyperglycemic values as hepatic glycogen content dropped. Following the rise in plasma glucose and fall in glycogen content, G-6-Pase specific activity increased and by 16 hr reached the high values characteristic of the diabetic animal. Hepatic ultrastructure was also changed as evidenced by an intrusion of elements of the SER into the dense glycogen masses; the result was dispersed glycogen closely associated with SER as seen in the diabetic animal. It is concluded that the hepatic response to insulin replacement in diabetic animals and diabetic onset in insulin-withdrawn animals is rapid and occurs through defined stages.

Animals↗
PubMed1984

Effects of glucagon on hepatic microsomal glucose-6-phosphatase in vivo.

The smooth endoplasmic reticulum (SER) has been implicated in glycogen deposition and depletion. It has been suggested that SER proliferation plays a role in elevated glucose release during rapid glycogenolysis (Striffler et al., Am. J. Anat. 160: 363, 1981). In these studies, the role of SER in glucagon-stimulated hepatic glucose release was examined by assessing changes in microsomal glucose-6-phosphatase (G-6-Pase) and membrane cholesterol to phospholipid ratios. In control fed rats given 6 i.p. injections of glucagon 350 micrograms/injection) at hourly intervals, percentage hepatic glycogen decreased nearly 30 fold, with liver homogenate G-6-Pase (U/mg protein) increasing 50% (p less than .02 relative to vehicle-injected controls) from .055 +/- .003 at 0h (n = 12) to .081 +/- .004 at 6h (n = 11). The increase in homogenate G-6-Pase was reflected in the isolated SER fraction by a 48% rise (p less than .01 relative to controls) in activity from a 0h value of .210 +/- .010 (n = 10) to a peak activity of .310 +/- .027 U/mg microsomal protein at 5 h (n = 12). G-6-Pase also increased in the rough endoplasmic reticulum (RER) reaching .242 +/- .023 U/mg protein at 4h (n = 14), but then declining to .209 +/- .019 U/mg protein at 6 h (n = 11). The changes in G-6-Pase were accompanied by alterations in the ratio of microsomal cholesterol to phospholipid, which decreased by 50% (p less than .002) in both RER and SER fractions signifying changes in membrane lipid environment. Ultrastructural analysis revealed a marked reduction in hepatic glycogen and conspicuous presence of elements of the SER in regions of the cytoplasm where glycogen was or presumably had been located.

Animals↗
PubMed1983

Observations on the role of smooth endoplasmic reticulumin glucocorticoid-induced hepatic glycogen deposition.

We have studied by quantitative electron microscopy the relationship of specific hepatic cellular organelles to glycogen synthesis using dexamethasone, a potent synthetic glucocorticoid, to induce glycogen deposition in livers of adrenalectomized rats. Chemical and ultrastructural glycogen determinations revealed that the livers of fasted adrenalectomized rats had very low glycogen levels. Dexamethasone caused a time-related increase in hepatic glycogen which was the result of increases in the number of hepatocytes depositing glycogen and the amount of glycogen in each cell. The surface density of smooth endoplasmic reticulum (SER) in centrilobular and periportal hepatocytes also increased after treatment with dexamethasone; this increase preceded glycogen deposition. The newly deposited glycogen was spatially associated with membranes of SER, and a continued increase in SER surface density was correlated temporally with the increasing glycogen volume density. In both centrilobular and periportal hepatocytes, the surface density of rough endoplasmic reticulum (RER) initially decreased after dexamethasone administration but later increased. These data support the hypothesis that dexamethasone-induced enhancement of SER is functionally associated with the increase in glycogen, and that although the initial increase in SER may occur through transformation of RER to SER, later increases in SER require synthesis of new membranes.

Adrenalectomy↗
PubMed1982

Morphological and biochemical observations on hepatic glycogen metabolism in mice on a controlled feeding schedule. I. Normal mice.

Changes in hepatocyte morphology were correlated with chemically measured liver glycogen, blood glucose, and plasma insulin levels in control-fed mice (6 hr fed, 18 hr fasted) sacrificed at various time intervals after initiation of a 6-hr meal. At initiation of feeding hepatic glycogen was low(0.05%) but deposition proceeded rapidly, reaching a maximum of 6.99 +/- 0.13% by the sixth hour. Glycogen was depleted during the subsequent fasting period, reaching the prefeeding levels by 24 hr. A relative hyperglycemia (140-192 mg/100/ ml) predominated during all stages of glycogen deposition and depletion until the 21st hour. Plasma insulin levels were maximum during feeding (63 +/- 7 microU/ml, 3 hr) with mild hyperinsulinemia (insulin greater than 16 microU/ml) occurring during glycogen depletion (9-21 hr). Histochemical determinations (PAS) showed lobular patterns of hepatic glycogen which correlated with chemically measured glycogen levels. Six hours after initiation of feeding, periportal cells showed intensely stained masses of glycogen while centrilobular cells showed relatively diffuse staining. At 24 hours after initiation of feeding (18 hr of fasting), no significant staining was observed in the hepatocytes. Ultrastructurally, during all stages of glycogen deposition and depletion, centrilobular cells were characterized by the presence of dispersed glycogen particles with elements of smooth endoplasmic reticulum (SER) between the particles, while periportal cells showed dense glycogen deposits with SER restricted to the periphery of the glycogen masses.

Animals↗
PubMed1982

Morphological and biochemical observations on hepatic glycogen metabolism in mice on a controlled feeding schedule. II. Streptozotocin-diabetic mice.

Morphological aspects of hepatic glycogen metabolism in streptozotocin (SZ) diabetic mice on a controlled feeding cycle (6 hr fed, 18 hr fasted) were studied and correlated with plasma glucose and insulin levels at various time intervals after feeding. Hepatic glycogen was low at initiation of feeding (approximately 0.05%) and increased to a maximum of 4.54 +/- 0.30% (N = 8) as compared to 6.90 +/- 0.20% (N = 12) in normal animals. Plasma glucose levels were similar to those of normal mice at initiation of feeding (80 +/- 5 mg/dl) but much higher during the feeding period (diabetic: 540 +/- 15 mg/dl, normal: 150 +/- 10 mg/dl). At the end of the feeding period, plasma glucose levels rapidly declined, reaching lower than normal levels. In contrast to insulin responses to feeding in normal animals, plasma insulin levels in SZ-diabetic mice remained very low, never exceeding 16 muU/ml. At maximum hepatic glycogen deposition, light microscopic studies showed atypical patterns of glycogen distribution with periportal cells having generally smaller-than-normal glycogen masses. Ultrastructural studies indicated that these cells contained more abundant quantities of smooth endoplasmic reticulum (SER) than is characteristically seen. The aberrant distribution patterns of glycogen observed in the diabetic mice provided morphological evidence for the proposal that the SER is involved in hepatic glycogenesis, with insulin deficiency resulting in abnormal functioning of the organelle.

Animals↗
PubMed1982

Subcellular responses of hepatocytes to diabetes in control-fed rats.

The biochemistry and ultrastructure of hepatocytes from streptozotocin-diabetic rats adapted to a controlled feeding schedule are described. The microsomal enzyme glucose-6-phosphatase (G-6-Pase), required for glucose release from the hepatocyte was monitored in homogenate preparations at times after the initiation of feeding in rats trained to a 6 h feeding, 18 h fasting cycle. G-6-Pase specific activity which is increased in ad lib fed diabetic rats was not further increased with time after the initiation of feeding in the feeding trained animals. However, the known elevation in G-6-Pase latent activity of the diabetic rat was reduced during the feeding cycle of times of minimum and maximum plasma glucose. Enzyme latency is a reflection of the multicomponent nature of G-6-Pase activity; therefore, plasma glucose levels may influence elements of that multicomponent system. Hepatic rough and smooth endoplasmic reticulum (RER + SER) fractions from the diabetic animals exhibited high and equivalent G-6-Pase specific activities independent of feeding or fasting. Ultrastructural observations of periportal hepatocytes showed a high content of SER correlated with the high G-6-Pase specific activity and closely associated with dispersed particles of glycogen at all times after the initiation of feeding. Also, an increase in SER was observed in the fasted normal animals although particulate glycogen was nearly absent. These findings support earlier work indicating that diabetes stimulates the proliferation of hepatic SER and that the membranes of this organelle are altered from those of the normal animal.

Animals↗
PubMed1982

Morphological and biochemical observations on hepatic glycogen metabolism in genetically diabetic (db/db) mice.

Changes in hepatocyte glycogen morphology, liver glycogen, and blood glucose and insulin levels were studied at various time points after initiation of feeding in 10 week old genetic diabetic (db/db) mice (n = 8) and their lean littermates adapted to a controlled feeding regimen (6 h fed - 18 h fast). In spite of hyperinsulinemic (insulin greater than or equal to 97.60 +/- 88 uU/ml) and hyperglycemic (glucose greater than or equal to 437.1 +/- 49.5 mg/dl) conditions favoring glycogen synthesis, feeding-induced hepatic glycogen deposition was less efficient in the diabetic mice. An apparent decreased ability to mobilize hepatic glycogen during fasting and maintenance of relatively high fasting liver glycogen concentrations were however attributable to the anti-glycogenolytic effects of high blood glucose and insulin concentrations. Histochemical determinations (PAS) on livers of db/db mice showed typical lobular patterns of glycogen distribution during deposition and depletion of the polysaccharide. At stages of maximum glycogen (6 h after initiation of feeding), periportal cells displayed intensely stained masses of glycogen with centrilobular cells staining more diffusely. Ultrastructural studies revealed smooth endoplasmic reticulum (SER) in close association with glycogen during its deposition and depletion. The preservation of normal glycogen morphology and SER-glycogen ultrastructure indicates that functioning of the SER in hepatic glycogen metabolism is normal in midly diabetic (db/db) mice.

Animals↗
PubMed1981

Effects of glucagon on hepatic glycogen and smooth endoplasmic reticulum.

The action of glucagon on hepatic glycogen and smooth endoplasmic reticulum (SER) was studied in samples of liver taken sequentially from anesthetized rats. The physiological state of each animal was assessed by continuously monitoring aortic blood pressure and blood lactatepyruvate ratios. High hepatic glycogen levels were established by using 10--12 hr fasted control-fed rats infused continuously with glucose. In rats receiving glucose only, hepatic glycogen levels remained above 5.0% during the 4-hr period of glucose administration. Centrilobular hepatocytes displayed an abundance of glycogen which often appeared dispersed with elements of SER between the glycogen particles. Periportal cells had dense clumps of glycogen with few vesicles of SER restricted to the periphery of the glycogen masses. The addition of glucagon to the glucose infusate caused a marked stimulation of glycogenolysis. In these rats, the hepatic glycogen level (X +/- SE) was 6.74 +/- .15% 1 hr after glucose and declined after initiation of glucagon infusion as follows: 5.86 +/- .29% (15 min), 4.89 +/- .26% (1 hr), 2.16 +/- .40% (2 hr), and 1.66 +/- .29% (3 hr). The fine structure of hepatocytes showed a dramatic response to the administration of glucagon. The glycogen regions of the cells were noticeably decreased in size and number of glycogen granules 3 hr after initiation of glucagon infusion, and SER was abundant in both periportal and centrilobular hepatocytes. The interpretation offered is that glucagon induces the formation of new SER membranes which participate in glycogen breakdown and/or glucose release from hepatocytes.

Animals↗
PubMed1980

Effects of actinomycin D on dexamethasone induced hepatic glycogen accumulation: morphological and biochemical observations.

Effects of inhibition of protein synthesis by actinomycin D (ACT) on the acute stimulation of hepatic gluconeogenesis and glucose-6-phosphatase (G6Pase) by the glucocorticoid, dexamethasone (DEX), in adrenalectomized (ADX) rats, were investigated using both morphological and biochemical means. Examination of ultra-thin sections of liver in the electron microscope revealed that ACT, administered alone or with DEX, resulted in a failure of hepatic glycogen accumulation to occur. Smooth endoplasmic reticulum (SER) appeared similar to that of the ADX-untreated animals, with occasional suggestions of increased amounts of membrane in ACT-treated animals. G6Pase activity in homogenates was increased, as was activation of the enzyme under all experimental conditions, when compared with ADX-untreated controls. The DEX-induced increase in G6Pase activity in SER failed to occur to any appreciable extent in ACT-treated animals. Plasma glucose levels increased slightly when ACT and DEX were present simultaneously. It is suggested that ACT countered the inductive effects of DEX on hepatic glycogen synthesis, but only partially suppressed acute stimulation of gluconeogenesis. A possible superinduction of G6Pase enzyme synthesis through increased efficiency of translation of extant mRNA is discussed. It is proposed that ACT inhibited the formation of appropriate SER membranes and/or other components necessary for glycogen accumulation.

Adrenalectomy↗
PubMed1979

Association of glycogen synthase phosphatase and phosphorylase phosphatase activities with membranes of hepatic smooth endoplasmic reticulum.

A detailed investigation was conducted to determine the precise subcellular localization of the rate-limiting enzymes of hepatic glycogen metabolism (glycogen synthase and phosphorylase) and their regulatory enzymes (synthase phosphatase and phosphorylase phosphatase). Rat liver was homogenized and fractionated to produce soluble, rough and smooth microsomal fractions. Enzyme assays of the fractions were performed, and the results showed that glycogen synthase and phosphorylase were located in the soluble fraction of the livers. Synthase phosphatase and phosphorylase phosphatase activities were also present in soluble fractions, but were clearly identified in both rough and smooth microsomal fractions. It is suggested that the location of smooth endoplasmic reticulum (SER) within the cytosome forms a microenvironment within hepatocytes that establishes conditions necessary for glycogen synthesis (and degradation). Thus the location of SER in the cell determines regions of the hepatocyte that are rich in glycogen particles. Furthermore, the demonstration of the association of synthase phosphatase and phosphorylase phosphatase with membranes of SER may account for the close morphological association of SER with glycogen particles (i.e., disposition of SER membranes brings the membrane-bound regulatory enzymes in close contact with their substrates).

Animals↗
PubMed1979

Effects of glucocorticoids on microsomal membrane synthesis in hepatocytes from adrenalectomized rats.

Biochemical and morphological studies were performed on livers from normal, adrenalectomized (ADX), and ADX and dexamethasone (DEX)-treated rats to investigate the effects of glucocorticoids on microsomal membrane synthesis. Overnight fasted normal, ADX and ADX rats treated 2 or 4 h with DEX received [3H]leucine and [14C]glycerol. Livers were removed, and tissue specimens were prepared for electron microscopy and tissue fractionation. Liver microsomal subfractions were prepared and subsequently washed to produce rough and smooth microsomal membranes. Radioactivity and membrane composition were determined, and glucose-6-phosphatase activity was measured in washed microsomal membranes. Adrenalectomy caused decreased microsomal membrane synthesis. Two and 4 h of DEX administration restored microsomal membrane synthesis to normal levels. ADX also caused an alteration in composition of the microsomal membranes (reflected in decreased phospholipid-protein ratios), which was restored to normal levels by 4 h after DEX administration. The earliest effects of the hormone on membrane synthesis were observed in smooth microsomes as part of a smooth endoplasmic reticulum (SER) proliferation. These findings were supported by observations made with the electron microscope. The proliferating SER was enriched in at least one component: glucose-6-phosphatase. Although the specific relationship of SER to glucocorticoid action remains unclear, the interpretation is offered that SER proliferation and alteration in glucose-6-phosphatase distribution are component parts of the total response of the hepatocyte to glucocorticoids.

Adrenalectomy↗
PubMed1979

Hepatic glucose-6-phosphatase activities and correlated ultrastructural alterations in hepatocytes of diabetic rats.

Cell fractionation, enzyme analysis, and electron microscopy were used to study the effects of streptozotocin-induced diabetes and insulin replacement on liver structure and function. In liver homogenates from diabetic rats, glucose-6-phosphatase (G-6-Pase) activity was stimulated about 2 1/2-fold over that found in normal animals. Analyses of isolated rough and smooth microsomes from diabetic rats for G-6-Pase activity showed a fourfold increase in the smooth microsomes and a small increase in enzyme activity in rough microsomes when compared with these fractions from control animals. Associated with the increased enzyme activity was a reduction in liver glycogen. Insulin treatment of the diabetic rats caused a fall in homogenate G-6-Pase levels to approximately normal values and stimulated the accumulation of hepatic glycogen. Administration of insulin to these animals also caused a decrease in G-6-Pase activity, which was most pronounced in the smooth microsomes. Studies with the electron microscope revealed ultrastructural alterations in livers of the diabetic rats, which were most striking in the periportal region of the lobule. Periportal hepatocytes from diabetic rats displayed dispersed particles of glycogen separated by cytoplasm rich in SER rather than dense masses of glycogen with little SER, as is characteristic of these cells in normal animals. Centrilobular cells from the diabetic animals displayed some disorganization of the RER and a dispersed pattern of glycogen with abundant SER, similar to the pattern found in these cells from normal animals. After insulin treatment the periportal cells appeared normal morphologically, whereas the centrilobular hepatocytes displayed regions of both dense masses and dispersed glycogen. In the glycogen masses, little SER was found; however, in the areas of dispersed glycogen particles, an abundance of this organelle was evident. We conclude from these studies that diabetes causes an increase in amount of hepatic smooth endoplasmic reticulum (SER), especially within periportal hepatocytes. The results of cell fractionation indicate that membranes of the smooth endoplasmic reticulum are enriched in G-6-pase. We interpret these results to indicate that diabetes causes hepatocytes to form additional smooth endoplasmic reticulum with specialized membranes, at least with respect to G-6-Pase. It is suggested that this cellular specialization is a response of the hepatocyte to the diabetic state, namely, a demand for increased hepatic glucose production and release into the blood stream, thus contributing to the hyperglycemia characteristic of this disease. Insulin administration to the diabetic animals reverses the above alterations.

Animals↗
PubMed1978

Alterations in hepatic fine structure after chronic exposure of rats to dexamethasone.

The objective of this study was to determine the effects of chronic dexamethasone (DEX) administration on hepatic ultrastructure and to correlate these changes with plasma lipoprotein levels. Electron microscopic studies were made of hepatocytes from male rats killed 1, 3 and 5 days after DEX (2 mg, twice per day) administration. Three days after treatment plasma lipoprotein levels were highest and hepatocytes contained regions of the cytosome rich in elements of the smooth endoplasmic reticulum (SER). Osmiophilic particles were present in the tubules and vesicles of the SER, in the saccules and vacuoles of the Golgi complex, in secretory vesicles near the cell surface and in the space of Disse. DEX treatments also caused hepatocytes to accumulate tightly packed masses of beta-particles of glycogen in some regions of the cell while other areas displayed dispersed glycogen particles that were associated with the SER. These observations are consistent with the hypothesis that glucocorticoids 1. cause an elevation of plasma lipoprotein levels by increasing hepatic synthesis and secretion of VLDL, which involves the sequential participation of the ER, the Golgi complex and exocytosis of VLDL-containing vacuoles into the space of Disse, and 2. produce a change in the nature of the association of glycogen particles with the SER membranes in response to the physiological state of the animal.

Animals↗
PubMed1978

Proliferation of smooth endoplasmic reticulum and induction of microsomal drug-metabolizing enzymes after ether or halothane.

Hepatic drug-metabolizing enzymes and hepatic ultrastructure were studied in rats after two hours of anesthesia with 1 MAC halothane or diethyl ether. Twelve hours after cessation of either anesthetic smooth endoplasmic reticulum was increased in centrilobular but not in periportal hepatocytes. This change persisted at 24- and 36-hour sampling times. Microsomal cytochrome P450 and cytochrome b5 decreased after halothane anesthesia (by 7 to 20 per cent of control). Diethyl ether caused increased cytochrome P450 and cytochrome b5 (27 and 18 per cent, respectively) at the 36-hour sampling time. NADPH cytochrome c reductase did not change significantly after either agent. The authors interpret these results to mean that both agents promote conversion of rough endoplasmic reticulum to smooth endoplasmic reticulum or, alternatively, that the anesthetics decrease degradation of smooth endoplasmic membranes. Since only ether caused an increase in the microsomal content of enzymes of the drug-metabolizing enzyme system, it is concluded that these two anesthetics act on hepatic cells by dissimilar mechanisms.

Animals↗