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E Hallberg

Publications and source records attributed to E Hallberg.

53 records · Page 3Linked to original sources
PubMed1990

On the identity of the xenobiotic-metabolizing form(s) of cytochrome P-450 in endocrine organs.

The adrenal cortex, the testes and the ovary metabolize polycyclic aromatic hydrocarbons (PAHs), e.g., 7,12-dimethylbenz[a]anthracene (DMBA). These activities have previously been shown to involve the cytochrome P-450 monooxygenase system [18-20]. In attempt to identify the form(s) of cytochrome P-450 involved, microsomes from these endocrine organs were subjected to SDS-gel electrophoresis, followed by immunochemical analysis using the Western blot technique. Antisera raised against the purified rat hepatic cytochrome P-450 isozymes a, b + e, c, d and PB-PCNE were tested. It was concluded that the electrophoretic mobilities of the immunoreactive bands obtained were not identical to the mobilities of the purified isozymes cytochromes P-450 a, b, c, d, e or PB-PCNE. These results indicate that the PAH-metabolizing monooxygenase(s) in these endocrine organs may involve a novel form(s) of cytochrome P-450.

Adrenal Cortex↗
PubMed1990

Cellular localization of cytochrome(s) P-450 metabolizing polycyclic aromatic hydrocarbons in the rat adrenal cortex.

Cells were dispersed from the capsular, as well as the inner portion of female rat adrenal glands and subsequently separated on discontinuous Percoll gradients. The adrenal cells were distributed within a density interval ranging from 1.016 to 1.075 g/cm3 and different subpopulations showed distinct morphological appearances in suspension, as well as in culture. The total cells from the inner portion of the adrenals metabolized [14C]7,12-dimethylbenz(a)anthracene at a rate of 4.04 pmol/min 10(6) cells and synthesized corticosterone in response to ACTH stimulation at a rate of 1.07 micrograms/hr/10(6) cells. These activities were 4- and 2.5-fold higher, respectively, than the corresponding activities in cells isolated from the capsular portion. 7,12-Dimethylbenz(a)anthracene monoxygenase activity and ACTH-stimulated steroidogenesis were enriched in two subpopulations of cells obtained on the Percoll gradient and were estimated to be 13.1 pmol/min/10(6) cells and 3.21 micrograms/hr/10(6) cells, respectively, in the most active fraction (at the 1.034/1.040 g/cm3 interface). On the basis of cellular morphology, density and steroidogenic properties, it was concluded that adrenal 7,12-dimethylbenz(a)anthracene monoxygenase activity is localized mainly in the cells of the zona fasciculata.

9,10-Dimethyl-1,2-benzanthracene↗
PubMed1990

Metabolism and toxicity of xenobiotics in the adrenal cortex, with particular reference to 7,12-dimethylbenz(a)anthracene.

The adrenal cortex contains high amounts of detoxifying enzymes, as well as generators and protectors of reactive oxygen species. The high content of cytochrome P-450 enzymes in the adrenal cortex together with its remarkable tendency to accumulate hydrophobic substances probably contributes to the extraordinary vulnerability of the gland to a number of xenobiotics. The best studied adrenocorticolytic compounds are the potent carcinogen 7,12-dimethylbenz(a)anthracene (DMBA) and its liver metabolite 7-hydroxymethyl-12-methylbenz(a)anthracene (7-OHM-12-MBA). Adrenocorticolysis generated by these agents in vivo as well as in vitro demonstrates high regioselective requirements and is strongly influenced by the presence of ACTH, steroids, cytochrome P-450 inhibitors and antioxidants. Furthermore, 7-OHM-12-MBA has been demonstrated to uniquely generate selective and massive oxidation of mitochondrial glutathione in cultured rat adrenal cells. The DMBA-induced adrenocorticolysis is thoroughly discussed in this review with particular emphasis on the metabolism of DMBA and the influence of various effectors. A working hypothesis involving a possible peroxidative mechanism is also presented.

9,10-Dimethyl-1,2-benzanthracene↗
PubMed1990

Experimental evaluation of polymerized Dacron grafts in the iliac position of pigs.

Three differently polymerized Dacron grafts were compared to ordinary Dacron grafts and polytetrafluoroethylene grafts in the iliac artery of pigs. The grafts were inserted end-to-side and left for 40 days. Explantation was performed after glutaraldehyde pressure fixation. Gross morphology, light microscopy, and scanning electron microscopy were used to examine the specimens. We concluded that the polymerized grafts behaved similarly to polytetrafluoroethylene grafts and had a very limited foreign body reaction. Endothelial-like cells covered most of the graft surface.

Animals↗
PubMed1990

Influence of effectors of prostaglandin metabolism on the toxicity induced by 7-hydroxymethyl-12-methylbenz(a)anthracene in cultured rat adrenal cells.

1. 7,12-Dimethylbenz(a)anthracene (DMBA) and 7-hydroxymethyl-12-methylbenz(a)anthracene (7-OHM-12-MBA), but not benzo(a)pyrene (BP), selectively produce necrosis in the two inner zones of the rat adrenal cortex and are toxic to cultured rat adrenocortical cells. 2. The toxicity induced by 7-OHM-12-MBA in the adrenocortical cells was partially prevented by the inhibitor of the cyclooxygenase activity of prostaglandin H synthetase, indomethacin. In contrast, indomethacin did not influence the effect of BP and DMBA on these cells. 3. Two other effectors of the prostaglandin metabolism, 5,8,11,14-eicosatetraynoic acid (ETYA) and nordihydroguaiaretic acid (NDGA), as well as the anti-inflammatory steroids cortisol and dexamethasone, partially protected against, whereas arachidonic acid and bradykinin exacerbated, the cytotoxicity induced by 7-OHM-12-MBA. 4. These results indicate that prostaglandin metabolism may be involved in the necrotic mechanism of 7-OHM-12-MBA in rat adrenal cortex.

5,8,11,14-Eicosatetraynoic Acid↗
PubMed1989

Selective oxidation of mitochondrial glutathione in cultured rat adrenal cells and its relation to polycyclic aromatic hydrocarbon-induced cytotoxicity.

Primary cultures of rat adrenal cells, as well as rat adrenals in vivo, are sensitive to the potent carcinogen 7,12-dimethylbenz[a]anthracene and its liver metabolite 7-hydroxymethyl-12-methylbenz[a]anthracene, whereas unmethylated polycyclic aromatic hydrocarbons like benzo[a]pyrene or benzo[a]anthracene are ineffective. The adrenocorticolytic potencies of the hydrocarbons are affected by adrenocorticotrophic hormone and various steroids, cytochrome P450 inhibitors, and antioxidants. In the present investigation digitonin was used to fractionate cultured rat adrenal cells. It was found that the mitochondria and cytosol of the cells contained 3-5 nmol/10(6) cells (approximately 15%) and 20-30 nmol/10(6) cells (approximately 85%) of the total soluble cellular glutathione equivalents, respectively. After exposing the cells to 7-hydroxymethyl-12-methylbenz[a]anthracene in the culture medium, a time- and concentration-dependent selective oxidation of mitochondrial glutathione was observed, whereas the effect on the cytosolic glutathione was negligible. Under the same conditions, 7,12-dimethylbenz[a]anthracene and benzo[a]pyrene were unable to alter the redox levels of the subcellular pools of glutathione. Omission of adrenocorticotrophic hormone lowered the oxidation of mitochondrial glutathione induced by 7-hydroxymethyl-12-methylbenz[a]anthracene about twofold. The results suggest that rat adrenal cells contain two separate pools of glutathione, one cytosolic and one mitochondrial, of which the latter is selectively influenced by 7-hydroxymethyl-12-methylbenz[a]anthracene. Moreover, it is concluded that rat adrenal cells offer a unique model system for general studies of the effects of a selective oxidation of mitochondrial glutathione on various cell functions. These effects may constitute early changes in cytotoxicity, preceding, e.g., membrane damage and loss of cytosolic components.

9,10-Dimethyl-1,2-benzanthracene↗
PubMed1989

Effect of 7-hydroxymethyl-12-methylbenz[a]anthracene and 1,3-bis-(2-chloroethyl)-1-nitrosourea on enzyme activities and oxidation of glutathione in cultured rat adrenal cells.

1. The activities of enzymes participating in the regeneration of reduced glutathione (GSH), and their subcellular distribution were studied in cultured rat adrenal cells. 2. It has previously been shown that the adrenocorticolytic agent 7-hydroxymethyl-12-methylbenz[a]anthracene (7-hydroxymethyl-12-MBA) causes a drastic and selective oxidation of mitochondrial GSH in rat adrenal cells. Treatment of the adrenal cells with 7-hydroxymethyl-12-MBA, resulted in a minor decrease in the content of cytochrome c oxidase, nicotinamide nucleotide transhydrogenase, isocitrate dehydrogenase and cytosolic GSH reductase, whereas the activity of lactate dehydrogenase and citrate synthase was unaffected. None of these effects were considered to be responsible for the massive oxidation of mitochondrial GSH induced by 7-hydroxymethyl-12-MBA. 3. 1,3-Bis-(2-chloroethyl)-1-nitrosourea (BCNU) was used to obtain rat adrenal cells cultures with inactivated cytosolic and mitochondrial GSH reductase. The oxidation of mitochondrial GSH, induced by 7-hydroxymethyl-12-MBA, was not dramatically enhanced by the inactivation of GSH reductase, indicating that this enzyme was not rate-limiting in the regeneration of GSH. 4. Fractionation of rat adrenal cells with increasing concentrations of digitonin resulted in an earlier release of citrate synthase in cells treated with 7-hydroxymethyl-12-MBA compared with controls. These results may indicate damage to mitochondrial membranes as a result of 7-hydroxymethyl-12-MBA treatment.

9,10-Dimethyl-1,2-benzanthracene↗
PubMed1988

Evaluation of peritoneal tube grafts in the inferior vena cava of the pig.

A tube graft 2.5 or 5 cm long, was constructed from the peritoneum of the anterior abdominal wall of 12 pigs. It was anastomosed end-to-end as an interposition graft in the infrarenal vena cava. The observation period was 4 months. Three of the six short grafts were venographically patent at 2 weeks, while all the long grafts were occluded. After 4 months two short grafts had recanalized, giving a patency rate of five out of six short grafts. No long grafts recanalized. In three of the patent specimens no clear tissue changes were found with light microscopy, while in the others changes of inflammation and fibrosis were noted. Scanning electron microscopy revealed good 'endothelialization' in two specimens, and partial 'endothelialization' in the others. No dilatation or severe stenosis of the patent grafts was seen. The occluded grafts remained only as a fibrous strand with sutures.

Anastomosis, Surgical↗
PubMed1987

Toxicity of 7,12-dimethylbenz[a]anthracene and 7-hydroxymethyl-12-methylbenz[a]anthracene and its prevention in cultured rat adrenal cells. Evidence for a peroxidative mechanism of action.

The adrenocorticolytic agent DMBA and its liver metabolite, 7-OHM-12-MBA, were investigated with respect to their mechanism of toxicity in cultured rat adrenal cells. Under proper growth conditions both hydrocarbons caused a reproducible and ACTH-dependent inhibition of steroidogenesis and cell death, similar to the effects of these agents on the rat adrenal in vivo. The toxicity of both DMBA and 7-OHM-12-MBA was partially prevented by antioxidants suggesting a common peroxidative mechanism of action. Studies with cytochrome P-450 inhibitors showed that toxicity of DMBA, but not 7-OHM-12-MBA, required a cytochrome P-450-dependent metabolic activation in order to be toxic. In addition, metyrapone, an efficient and specific inhibitor of the mitochondrial 11 beta-hydroxylase, provided protection against DMBA-induced toxicity, which is in agreement with previous observations that adrenal necrosis caused by DMBA apparently originates in mitochondria. It is proposed that both 7-OHM-12-MBA and DMBA, the latter after metabolism to mainly phenols, act as pseudosubstrates for steroid hydroxylases and initiate peroxidative damage through hydroxylase-generated superoxide anion, and/or hydrogen peroxide. These results indicate that both adrenal and hepatic metabolism of DMBA are potentially important in DMBA-induced adrenocorticolysis in vivo.

9,10-Dimethyl-1,2-benzanthracene↗
PubMed1983

Metabolism and toxic effects of 7,12-dimethyl-benz[a]anthracene in isolated rat adrenal cells.

Isolated rat adrenal cells in tissue culture, showing ACTH-induced corticosterone synthesis, were used as a model system for the study of adrenal metabolism and toxicity of 7,12-dimethylbenz[a]anthracene (DMBA). DMBA was metabolized at a rate of 10 pmol/min/10(6) cells and with a Km of 0.5 microM. Metabolite patterns and sensitivity to various AHH inhibitors suggest the involvement of an epoxide intermediate. In agreement with this proposal DMBA metabolite(s) were bound to cellular protein at a rate which was related to the AHH activity. Adrenal AHH was found to be insensitive to ACTH during a period of 24 h. Using ACTH-induced corticosterone synthesis as an indicator of cell damage the hepatic metabolite 7-hydroxymethyl-12-methyl-benz[a]anthracene was shown to be significantly more toxic than the parent compound DMBA. It is concluded that DMBA-dependent adrenal damage in vivo is due mainly to the liver metabolite 7-hydroxymethyl-12-methyl-benz[a]anthracene (7-OHM-12-MBA), possibly after secondary metabolic activation in the adrenal.

9,10-Dimethyl-1,2-benzanthracene↗
PubMed1981

Fine-structural characteristics of the antennal sensilla of Agrotis segetum (Insecta: Lepidoptera).

The turnip moth Agrotis segetum possesses seven different types of sensilla: four single-walled (SW), one double-walled (DW), one terminal-pore (TP), and one poreless sensilla (NP). The SW 1 and SW 2 sensilla have the same external appearance, being long and slender, but differ in the branching pattern of the sensory processes: unbranched and branched in SW 1 and SW 2, respectively. The SW 3 sensilla are shorter, sickle-shaped, and contain a large number of branches from the sensory processes. These three sensillar types are innervated by 2--3 sensory cells. The SW 4 sensilla are raisin-shaped and possess three profusely branched sensory processes. The DW sensilla are short and have apical slit-like pores. This sensillar type has 5--6 sensory processes. The TP sensilla possess five sensory processes, one of them terminates basally in a tubular body, the others in the apical part of the long cuticular bristle. The NP sensilla are stout and have apical conelike structures. Two of the sensory processes terminate in the apical part, the third proximally. The third sensory process has a lamellar pattern. The fine structure indicates the following functions: SW and DW sensilla: chemoreception; TP sensillum: chemoreception and mechanoreception; NP sensillum: thermoreception and hygroreception.

Animals↗
PubMed1977

The fine structure of the compound eyes of mysids (crustacea: mysidacea).

The ultrastructure of the compound eyes of five species of mysids (Crustacea: Mysidacea), Praunus flexuosus, Siriella norvegica, Mysidopsis gibbosa, Neomysis integer and Erythrops serrata, is described. The ommatidia are constructed on a common plan, but there are considerable differences in detail. Common features include the arrangement of the cornea, crystalline cone and the basement membrane. The number of retinular cells differ: in Neomysis and Erythrops there are seven, whereas in the other species there are eight, the eighth cell forming a distal rhabdom, which consequently is lacking in the ommatidia of Neomysis and Erythrops. Another difference is the epirhabdom, which is lacking in Erythrops, but present in the other species. The epirhabdom is an extracellular structure, probably serving as a dioptric element. The pigment arrangement is similar in the first four species. The pigment shield consists of the distal pigment, distal reflecting pigment, proximal pigment (in the retinular cells) and the proximal reflecting pigment. The distal and proximal pigments are dark screening pigments. In addition to these, there are basal red pigment cells, which are mainly located below the basement membrane. In Erythrops there are three kinds of pigment cells: distal pigment cells, distal reflecting pigment cells and basal red pigment cells. Besides the basal red pigment cells, the distal pigment cells contain red pigment granules.

Animals↗
PubMedDate not supplied

Toxaphene: accumulation in the adrenal cortex and effect on ACTH-stimulated corticosteroid synthesis in the rat.

Uptake and distribution of [14C]toxaphene was studied in the adrenals of rats using whole-body autoradiography. An accumulation of radioactivity was seen in the adrenal cortex (zona fasciculata) 1-24 h after a single gavage of [14C]toxaphene (16 mg/kg b.w.). In in vitro studies toxaphene was found to inhibit ACTH-stimulated corticosterone synthesis in the cultured rat adrenocortical cells (IC50 2.8 X 10(-5) M). Moderate but significant inhibition (P less than 0.001) of ACTH-stimulated corticosterone synthesis was also observed in the adrenocortical cells isolated from rats after a prolonged exposure (5 weeks) to low levels (1.2 ppm) of toxaphene in feed. The results indicate a direct adrenotoxic effect of toxaphene.

Adrenal Cortex↗
PubMedDate not supplied

Transplantation of preconditioned intestinal grafts is associated with lower inflammatory activation and remote organ injury in rats.

Reperfused grafts--particularly the intestine--release free radicals and cytokines into the systemic circulation. The type of discharge, which is greatly dependent on the local injury, may also induce inflammatory activation in distant organs and leading to multiple system and organ failure. It has been suggested that intestinal grafts from tacrolimus (TRL)-pretreated donors show improved morphology and microcirculation. We studied whether transplantation of intestines from TRL-pretreated donors influenced inflammatory response and remote organ injury posttransplantation. Donor Sprague Dawley rats received TRL or saline (controls) intravenously at 6 hours prior to graft harvest. The intestinal grafts were preserved in saline for 3 hours before transplantation. At 6 and 12 hours postreperfusion hepatic and renal cortical microcirculation were assessed using laser-Doppler flowmetry (n = 8-12 per group). Blood pressure was measured; liver, kidney, and serum samples were obtained. We analyzed hepatic and renal ICAM-1 expression and caspase-3-like activity as well as plasma content of tumor necrosis factor-alpha and interleukin-6. Pretreated graft recipients had higher mean arterial pressure (82 +/- 10 vs 51 +/- 17 mm Hg, P < .05) and renal perfusion at 6 hours whereas liver perfusion was similar at both 6 and 12 hours. Liver and renal functions were also superior among recipients of pretreated grafts. Both caspase-3-like activity and ICAM-1 expression in liver and kidney were lower in pretreated graft recipients. Plasma IL-6 levels were lower in animals receiving pretreated grafts. Transplantation of intestines from TRL-pretreated donors was followed by a lower systemic inflammatory response, improved organ function and decreased remote injury early posttransplantation compared with animals receiving grafts from untreated donors.

Animals↗