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C Eriksson

Publications and source records attributed to C Eriksson.

18 recordsLinked to original sources
PubMed1992

Effects of glutathione-modulating agents on the covalent binding and toxicity of dichlobenil in the mouse olfactory mucosa.

Twenty-four hours following injection of a single dose of the herbicide dichlobenil (2,6-dichlorobenzonitrile) in C57Bl/6 mice a steep dose-response curve for the histopathological toxicity in the olfactory mucosa was observed. Four hours following injection of a toxic dose of [ring-14C]dichlobenil (12 mg/kg) the covalent binding in the olfactory mucosa was 26 times higher than that in the liver. A dose-dependent decrease of nonprotein sulfhydryls (mainly glutathione, GSH) in the olfactory mucosa was observed 2.5 hr following injection of dichlobenil (6, 12, 25 mg/kg). The synthetic GSH precursor N-acetyl-L-cysteine decreased both the dichlobenil-induced toxicity and the covalent binding, whereas N-acetyl-D-cysteine had no effect. No protective effects of the cyanide antidotes nitrite, thiosulfate, or superoxide dismutase on the dichlobenil-induced toxicity were observed. In mice given the GSH-depleting agent phorone and a subtoxic dose of dichlobenil (6 mg/kg), an extensive toxicity and an increased covalent binding in the olfactory mucosa were demonstrated. Autoradiography showed no change in the distribution of covalent [14C]dichlobenil binding to nontarget tissues of phorone-treated mice. In conclusion, the results demonstrate a relationship between the degrees of covalent binding, GSH depletion, and toxicity of dichlobenil in the olfactory mucosa. Hence, the level of GSH appears to be of importance for the dichlobenil-induced toxicity in the olfactory mucosa.

Acetylcysteine↗
PubMed1992

Tissue-binding and toxicity of compounds structurally related to the herbicide dichlobenil in the mouse olfactory mucosa.

The herbicides dichlobenil (2,6-dichlorobenzonitrile), chlorthiamid (2,6-dichlorothiobenzamide) and their environmental degradation product 2,6-dichlorobenzamide are irreversibly bound and toxic to the olfactory mucosa following single injections in mice (Brandt et al., Toxicology and Applied Pharmacology 1990, 103, 491-501; Brittebo et al., Fundamental and Applied Toxicology 1991, 17, 92-102). In the present study, autoradiography showed an irreversible binding of radioactivity in the olfactory mucosa (preferentially in the Bowman's glands) in C57Bl/6 mice treated with the 14C-labelled analogues [14C]2,6-difluorobenzonitrile ([14C]DFBN) and [14C]2,6-difluorobenzamide ([14C]DFBA). Therefore the toxicity of DFBN, DFBA and of some structurally related compounds including benzonitrile (BN) and the herbicides bromoxynil (3,5-dibromo-4-hydroxybenzonitrile) and ioxynil (3,5-diiodo-4-hydroxybenzonitrile) in the mouse olfactory mucosa was examined. No histopathological changes in the olfactory mucosa or in the liver were observed following a single ip dose of any of these compounds [0.145 mmol/kg (all compounds); 0.58 mmol/kg (DFBN, DFBA and BN)]. Also in mice treated with the glutathione-depleting agent phorone, none of these compounds induced any histopathological changes in the olfactory mucosa. The covalent binding of [14C]DFBN in the olfactory mucosa was 16 times lower than an equimolar toxic dose of [14C]dichlobenil, suggesting a low rate of metabolic activation of DFBN in the olfactory mucosa or a low reactivity of the DFBN metabolites formed. The results of this study thus show that single doses of DFBN, DFBA, BN, IX and BX, compounds structurally related to the potent olfactory toxicant dichlobenil, do not elicit acute toxicity in the olfactory mucosa of mice.

Animals↗
PubMed1991

Epithelial binding of 1,1,2,2-tetrachloroethane in the respiratory and upper alimentary tract.

The bioactivation and binding of 14C-labelled 1,1,2,2-tetrachloroethane (TCE) in the tissues of C57B1 mice were studied. As shown by autoradiography with heated and organic solvent-extracted tissue sections of i.v. injected mice, a high and selective localization of bound metabolites occurred in the nasal olfactory mucosa, preferentially in the Bowman's glands. High levels of bound metabolites were also present in epithelia of the trachea, bronchi and bronchioli and in the squamous epithelia of the oral cavity, tongue and esophagus. An epithelial binding was observed in tissue slices incubated with 14C-TCE. Incubation of 14C-TCE with homogenates of the olfactory mucosa and liver showed that the olfactory mucosa had a higher ability to activate 14C-TCE into products that become irreversibly bound to protein. Addition of metyrapone, glutathione or sodium dithionite to the incubations decreased the level of irreversible binding, suggesting that the activation of TCE to reactive products is mediated via an oxidative cytochrome P-450 dependent process in the olfactory mucosa.

Adrenal Cortex↗
PubMed1991

Metabolic activation of the herbicide dichlobenil in the olfactory mucosa of mice and rats.

The metabolic activation of the herbicide dichlobenil (2,6-dichloro[ring-14C]benzonitrile) in the olfactory mucosa of C57BL mice and Sprague-Dawley rats was examined. In homogenates of the olfactory mucosa (mouse 1000 x g supernatants; rat microsomes), dichlobenil was metabolized and covalently bound to protein. The apparent Km, Vmax and V/K values showed that the olfactory mucosa had both a higher affinity for dichlobenil and a higher capacity/mg protein to activate dichlobenil in comparison to the liver. The covalent binding was dependent on NADPH and was inhibited by the addition of dithionite, metyrapone and glutathione indicating an oxidative cytochrome P-450 dependent activation of dichlobenil into an electrophilic intermediate. The covalent binding was also inhibited by the addition of superoxide dismutase whereas catalase, mannitol or dimethylsulfoxide had no effect indicating the involvement of O2- but not of H2O2 or OH. in the activation. In explants of the olfactory mucosa incubated with [14C]dichlobenil a preferential covalent binding was observed in the Bowman's glands suggesting an activation of dichlobenil in these structures. The highly efficient metabolic activation of dichlobenil to reactive intermediates in the olfactory mucosa is suggested to be of importance for the potent dichlobenil-induced toxicity in this tissue.

Animals↗
PubMed1991

Metabolic activation of halogenated hydrocarbons in the conjunctival epithelium and excretory ducts of the intraorbital lacrimal gland in mice.

Autoradiographic studies were performed to determine the localization of irreversibly bound radioactivity in the eyes and accessory structures of mice exposed to 14C-labelled organic solvents in vivo or in vitro. A selective localization of bound radioactivity was observed in the conjunctival epithelium of mice given i.v. injections of 1,2-dibromoethane, chloroform, carbon tetrachloride or bromobenzene. Similar results were observed after instillation of chloroform or carbon tetrachloride in the conjunctival sac and after incubation of eyelids with the labelled compounds in vitro. A high level of irreversibly bound radioactivity was also observed in the excretory ducts of the intraorbital lacrimal glands of mice exposed to 1,2-dibromoethane in vivo and in vitro. After incubation of 14C-labelled 1,2-dibromoethane or chloroform with homogenates prepared from rat conjunctiva, the presence of irreversibly protein-bound radioactivity was detected. The results indicate that the conjunctival epithelium can metabolically activate halogenated organic solvents into products that bind to the tissue. The significance of a metabolic activation of chemicals in the pathogenesis of chemically induced lesions in the conjunctiva merits further attention.

Animals↗
PubMed1991

Toxicity of 2,6-dichlorothiobenzamide (chlorthiamid) and 2,6-dichlorobenzamide in the olfactory nasal mucosa of mice.

The toxic effects of the herbicide chlorthiamid (2,6-dichlorothiobenzamide) and its major environmental metabolite 2,6-dichlorobenzamide (DCBA) were examined in the nasal passages of C57Bl mice following single ip injections. Chlorthiamid (12.25, and 50 mg/kg) induced an extensive destruction of the olfactory region, similar to that previously observed with the analogue dichlobenil (2,6-dichlorobenzonitrile). Necrosis of Bowman's glands was evident first, whereas degeneration and necrosis of the olfactory neuroepithelium developed less rapidly. The lesions were most severe in the dorsomedial region of the nasal cavity. At longer post-treatment intervals, the olfactory epithelium was replaced by a respiratory-like epithelium, and there was fibrosis of the lamina propria. DCBA was also toxic to the olfactory region (100 mg/kg), inducing necrosis of the Bowman's glands and the neuroepithelium in the dorsomedial region of the nasal cavity. No lesions were observed in other parts of the nasal cavity or in the liver after administration of chlorthiamid or DCBA. Chlorthiamid (IC50 = 51 microM), but not DCBA, inhibited the covalent binding of 14C-labeled dichlobenil in the olfactory mucosa in vitro. It is proposed that the toxic effects of chlorthiamid and dichlobenil in the olfactory mucosa are mediated by common or closely related metabolites.

Animals↗
PubMed1990

Activation and toxicity of bromobenzene in nasal tissue in mice.

Autoradiography of mice injected i.v. with bromobenzene-14C (BB; 25 mumol/kg body wt) revealed a high concentration of non-volatile metabolites in the olfactory mucosa and in the glands around the maxillary sinuses. As determined with solvent-extracted tissue sections, there was a high level of irreversibly bound metabolites in the Bowman's glands in the olfactory mucosa, while the level of bound metabolites was low in the glands around the maxillary sinuses. Histopathological examination of the nose region of mice given a single i.p. dose of unlabelled BB (greater than or equal to 4.8 mmol/kg body wt) revealed degeneration and necrosis of the glands of Bowman. Degenerative changes in the olfactory epithelium were also observed. Moreover, focal degeneration and necrosis were found in the lateral nasal glands (greater than or equal to 4.8 mmol/kg body wt). Cyst-like dilatation of acini was observed in the lateral nasal glands and in the maxillary glands located around the maxillary sinus. Incubation of BB (26 microM) with a homogenate prepared from the olfactory mucosa revealed an irreversible binding, which clearly exceeded that of the liver. It is suggested that BB is activated in situ to a cytotoxic metabolite that reacts with the glands of Bowman. The specific toxicity observed in the lateral nasal glands correlated with a high concentration of non-volatile but extractable metabolites in these glands.

Animals↗
PubMed1990

Composition of faeces from human subjects consuming diets based on conventional foods containing different kinds and amounts of dietary fibre.

The stool-bulking effect of dietary fibre (DF) is well-documented and believed to be important in the postulated beneficial effect of DF on human health. The aim of the present study was to investigate the digestibility of DF in relation to its stool-bulking properties and to study possible mechanisms for this effect. Four diets, based on conventional foods only, were studied in balance experiments on human subjects. Diet A contained DF mainly from whole-grain cereals while diets B1 and B2 contained DF mainly from pulses, vegetables and fruit. Diet C was a low-fibre diet. Faeces was fractionated into four fractions, each enriched in one of the following three components: undigested DF (fractions 1 + 2), faecal bacteria (fraction 3) and soluble components (fraction 4). The digestibility of DF in diets A, B1 and B2 was 0.62, 0.88 and 0.90 respectively. Subjects consuming diet A excreted slightly more fraction 3 than subjects consuming the other diets. Thus, the statement that DF of high digestibility stimulates microbial growth in the gut was not supported. The water-holding capacity of fraction 1 was studied in vitro and was found to be low. It is suggested that undigested soluble DF is important in the stool-bulking properties of DF.

Adult↗
PubMed1977

Affinity chromatography of lipoxygenases.

A number of aminohexyl agarose derivatives of unsaturated fatty acids have been prepared and evaluated as materials for the affinity chromatography of soybean and pea lipoxygenases. A practical method for a one-stage purification of soybean lipoxygenase-1, with a purification factor of 16, is described, using either linolenate or docosa-4,7,10,13,16,19-hexaenoate as ligands. Results show that alleged competitive inhibitors do not cause sharp elution from the affinity column, and that there is an increasing specificity of binding and sharpness of elution as the proportion of unsaturation in the ligand is increased. These results are discussed in terms of the relative importance of the types of bonding involved in enzyme-substrate binding.

Chromatography, Affinity↗
PubMed1977

Preliminary clinical evaluation of the effect of small electrical currents on the healing of jaw fractures.

A clinical investigation has been carried out into the effect of small electrical currents on the healing of mandibular fractures. Electrical stimulation of fracture healing was carried out in 40 patients with a direct current of 10 or 20 microamperes delivered through a platinum electrode. An equal number of patients with similar fractures were selected as controls. Rate of repair was assessed by measuring the mobility of the fracture. Serum phosphatase and calcium were regularly measured at intervals in both groups after reduction and suggested that alkaline phosphatase activity increased in the stimulated group. The repair process was enhanced in the electrically stimulated fractures compared to the controls in the first 10-14 days after reduction.

Alkaline Phosphatase↗
PubMed1977

Bone mineral and surface charge.

A triple association has been observed between a high negative surface charge, bone morphogenetic activity, and in vitro recalcificaiton in implants of demineralized bone matrix. Proplast fills with bony tissue when implanted in the body and shows the same triple association. The higher the negative surface charge, the greater is the mass of new bone induced and the higher degree of mineralization when placed in a calcifying solution in vitro. Further investigations are necessary to determine whether in implants of demineralized bone, a high negative surface charge may cause the formation of discrete calcium deposits or whether it triggers the invading primitive cells to differnetiate and produce bone, or both.

Animals↗
PubMed1975

Some factors affecting bone formation: a review.

Two separate methods exist at present to induce new bone formation. One utilises the implantation of specific materials, which may be of biological or non-biological origin. The other is based on the finding that bony tissue responds to very small electrical currents by stimulating osteogenesis at the negative electrode. This article discusses these methods in detail.

Animals↗
PubMedDate not supplied

Bone morphogenesis and surface charge.

The electrophoretic mobility of variously treated bone specimens, with and without bone morphogenetic activity, has been measured in physiological solutions. The Bone Morphogenetic Principle appears to be associated with a minimum negative surface charge on the implant that corresponds to that of normal undemineralized cortical bone in saline. Demineralization of cortical bone in 0.6 N HCI at 2 degrees consistently increases the bone negative surface charge, and biologically produces an implant with morphogenetic activity. It is suggested that through the mediation of the positively charges ionic layer surrounding the negative implant that the negatively charged mesenchymal cell is able to reside in very close contact with the surfaces of the implant. The binding force can be expected to be directly proportional to the degree of negativity of the implant. However, implants with a positive zeta potentaial will be surrounded by ions with a net negative charge so discouraging the stable positioning of mesenchymal cells in close contact with the implant. The negative surface charge corresponding to that of untreated cortical bone is apparently borderline in permitting such a close contact for a sufficiently long period of time for differentiation to follow.

Bone Development↗