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Ronald G. Thurman - One of the best experts on this subject based on the ideXlab platform.
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chronic ethanol treatment induces h2o2 production selectively in pericentral regions of the Liver Lobule
Alcoholism: Clinical and Experimental Research, 1992Co-Authors: U K Misra, Blair U Bradford, Jeffrey A Handier, Ronald G. ThurmanAbstract:Chronic treatment with ethanol damages pericentral regions of the Liver selectively, and reactive oxygen species such as H2O2 may be involved in the mechanism of hepatotoxicity. To test this idea, the effect of chronic treatment with ethanol on rates of H2O2 production was measured in tissue cylinders isolated from periportal and pericentral regions of Livers from ethanol-treated rats. Rates of hydrogen peroxide production, assessed from the oxidation of methanol to formaldehyde by catalase-H2O2, were similar in tissue cylinders isolated from periportal regions in control and ethanol-treated rats. In contrast, rates of H2O2 production were over 4-fold higher in tissue isolated from pericentral regions of Livers from ethanol-treated than control animals (1.7±0.5 vs. 0.4 ±0.3 nmol/min/mg protein, respectively). Rates of H2O2-generating acyl CoA oxidase activity were equivalent in tissue cylinders from periportal regions of Livers from both groups (approximately 2 nmol/min/mg protein), but were over 2-fold higher in tissue cylinders from pericentral regions of Livers from ethanol-treated rats than from controls. In contrast, catalase activity was increased nearly 2-fold in homogenates from both periportal and pericentral regions by ethanol treatment while glutathione peroxidase activity was decreased significantly in both regions. These data demonstrate that ethanol increases H2O2 generation in pericentral regions of the Liver Lobule in part by elevating rates of peroxisomal β-oxidation of acyl CoA compounds and are consistent with the hypothesis that local increases in H2O2 production may be involved in the mechanism of ethanol-induced hepatotoxicity.
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hormones increase oxygen uptake in periportal and pericentral regions of the Liver Lobule
American Journal of Physiology-gastrointestinal and Liver Physiology, 1992Co-Authors: Takakatsu Matsumura, H Yoshihara, Yoshiyuki Takei, F C Kauffman, R A Jeffs, S Nukina, T Hijioka, R K Evans, Ronald G. ThurmanAbstract:The effect of several hormones known to alter intracellular free Ca2+ on rates of O2 uptake in periportal and pericentral regions of the Liver Lobule was studied in the perfused Liver. Regional O2 uptake was measured by stopping the flow and monitoring the decrease in O2 concentration. When perfusion was in the anterograde direction, basal rates of O2 uptake were two to three times higher in periportal than in pericentral regions, and phosphorylase alpha activity, which increases as a function of intracellular free Ca2+ levels, was higher in periportal regions. In contrast, when perfusion was in the retrograde direction, rates of O2 uptake were two to three times greater in pericentral regions. Infusion of epinephrine (0.1 microM) or angiotensin II (5 nM) increased the rate of O2 uptake nearly exclusively in downstream areas of the Lobule where O2 tension was low. When perfusions were in the anterograde direction, epinephrine increased phosphorylase alpha activity significantly only in pericentral regions. Stimulation of O2 uptake by epinephrine was blocked by the alpha-adrenergic receptor blocker phentolamine (1 microM) but not by the beta-receptor blocker propranolol. Thus hormones that increase intracellular calcium stimulate O2 uptake predominantly in regions of the Liver Lobule where O2 tension is lowest, supporting the hypothesis that oxygen tension regulates O2 uptake in the Liver via mechanisms involving intracellular free Ca2+.
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oxygen tension is a major determinant of hepatotoxicity due to 2 ethylhexanol in isolated tissue cylinders from periportal and pericentral regions of the Liver Lobule from phenobarbital treated rats
Toxicology and Applied Pharmacology, 1991Co-Authors: Decai Liang, U K Misra, Barbara J Keller, Ronald G. ThurmanAbstract:Abstract 2-Ethylhexanol, a metabolite of the commonly used plasticizer di(ethylhexyl)phthalate, was shown to cause toxicity exclusively to periportal regions of the perfused Liver (Keller et al., 1990, J. Pharmacol. Exp. Ther. , 252, 1355–1360.) To determine whether this toxicity was due to local oxygen tension or to drug deLivery, isolated cylinders (plugs) of periportal and pericentral regions of the Liver Lobule from rats pretreated with phenobarbital were collected with a micropunch following brief perfusion of the organ. Plugs were 0.2 mm wide and 0.5 mm long and weighed between 0.5 and 1 mg each. Following incubation for at least 2 hr in Eagle's medium, they were judged viable based on production of urea at high rates and minimal leakage of lactate dehydrogenase (LDH). Plugs could be cultured for up to 24 hr with minimal loss of activity. Urea synthesis from ammonium chloride (3 m m ) by plugs incubated in Krebs-Henseleit buffer equilibrated with 95% O 2 :5% CO 2 was proportional to protein concentration and was linear with time for up to one hour at rates around 75 μmol/g/hr. Icubation of plugs with 2-ethylhexanol (0.1 to 3 m m ) diminished urea synthesis in a dose-related manner (half-maximal effect = 0.5 m m ). Ethylhexanol also caused extensive cell damage assessed from LDH leakage in incubations at 800 μ m O 2 but significantly less injury at 200 μ m O 2 . Concomitantly, urea synthesis was inhibited by ethylhexanol by over 80% at 800 μ m O 2 but less than 50% at 200 μ m O 2 . Plugs isolated from both regions of the Liver Lobule were affected similarly by ethylhexanol and O 2 . Taken together, these data indicate that ethylhexanol toxicity is dependent on oxygen tension in isolated sublobular regions of the Liver Lobule, and therefore it is unlikely that drug deLivery can explain the selective injury to periportal regions in studies with the perfused Liver.
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regulation of urea synthesis in sublobular regions of the Liver Lobule by oxygen
Biochimica et Biophysica Acta, 1990Co-Authors: Yoshiyuki Takei, Frederick C. Kauffman, U K Misra, Hirofumi Yamanaka, Ronald G. ThurmanAbstract:Abstract Periportal and pericentral regions of the Liver Lobule were isolated from perfused rat Liver using a micropunch and incubated in Krebs-Henseleit buffer (pH 7.6) containing 2% poly(ethylene glycol) in Eagle's basal medium, PMSF (50 μg/ml) and leupeptin (20 μg/ml) for 2 h at 25°C under and O 2 /CO 2 (95:5%) gas phase. Maximal rates of urea production from ammonium chloride were 96.4 ± 8.7 and 32.8 ± 5.4 μg per h at 800 and 200 μM O 2 . Thus, urea synthesis was 2ndash;3-times greater at high than low O 2 tension is plugs from periportal and pericentral regions of the Liver Lobule.
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phagocytosis by kupffer cells predominates in pericentral regions of the Liver Lobule
American Journal of Physiology-gastrointestinal and Liver Physiology, 1990Co-Authors: J Te M Koppele, Ronald G. ThurmanAbstract:These studies were designed to determine whether particle phagocytosis could be monitored from the surface of the perfused Liver. To achieve this goal, decreases in reflected light were measured during phagocytosis of colloidal carbon particles. Livers were illuminated with 623-nm light via a relatively large fiber-optic light guide (tip diam 2 mm), and reflected light was monitored continuously. A decrease in reflected light was observed when carbon was infused that was proportional to the influent carbon concentration. Initial changes in reflected light were linearly related to rates of carbon uptake by Kupffer cells. Subsequently, rates of carbon uptake were determined from changes in reflected light in periportal and pericentral regions of the Liver Lobule with miniature fiber-optic light guides. In perfusions in the anterograde direction, rates of carbon uptake were approximately 80% higher in pericentral than periportal regions of the Liver Lobule. This pattern was reversed when Livers were perfused in the retrograde direction. Thus particle phagocytosis predominates in downstream regions of the Liver Lobule. Because decreasing the pH of the influent perfusate increased carbon uptake, the pH gradient over the Liver Lobule may be involved in the regulation of particle uptake at the sublobular level.
Takeshi Shiga - One of the best experts on this subject based on the ideXlab platform.
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ethanol induces heterogeneous reduction of cytochrome aa3 within perfused rat Liver Lobule assessed using microspectroscopy
Alcohol and Alcoholism, 1995Co-Authors: Shengsong Chen, Harumasa Yoshihara, Akitoshi Seiyama, Noboru Harada, Sunao Kawano, Shingo Tsuji, Hideyuki Fusamoto, Takenobu Kamada, Takeshi ShigaAbstract:The redox state of cytochrome aa3 was measured at microspots (20 microns diameter) within the Lobule of perfused rat Livers, using reflectance microspectroscopy, and the effect of ethanol infusion on sublobular distribution of the redox states was evaluated. A sigmoidal relationship was observed between oxygen deLivery and the reduction of cytochrome aa3 in both the periportal and pericentral regions of the Liver Lobule when the influent O2 concentration was decreased in a graduated manner. This sigmoidal curve was shifted to the more reduced state by ethanol infusion, with ethanol (25-100 mM) increasing the degree of cytochrome aa3 reduction in a dose-dependent manner according to the distance from the periportal region along a sinusoid. This increase was spatially heterogeneous within a Liver Lobule. These data indicate that ethanol accelerates cytochrome aa3 reduction, with a distinct gradient of reduction along sinusoids but a heterogeneous distribution within the Liver Lobule.
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Measurement of redox states of mitochondrial cytochrome aa3 in regions of Liver Lobule by reflectance microspectroscopy.
The American journal of physiology, 1993Co-Authors: S S Chen, H Yoshihara, Akitoshi Seiyama, Noboru Harada, Sunao Kawano, Hideyuki Fusamoto, Takenobu Kamada, M Watanabe, H Kosaka, Takeshi ShigaAbstract:To evaluate the sublobular distribution of oxygen tension, the redox states of mitochondrial cytochrome aa3 were assessed in local regions of the Liver Lobule by reflectance microspectroscopy. The reflected light from two focused microspots (20 microns in diam) on the surface of the perfused Liver, placed on the stage of microscope, was conducted to the spectrophotometer with two separate light guides, giving the reflectance spectra. The redox state of cytochrome aa3 was calculated from the difference in reflectance between 603 and 630 nm. The degree of cytochrome reduction increased with the stepwise decline of the influent or effluent oxygen concentrations. The local oxygen concentration in periportal region for the half-maximal reduction of cytochrome aa3 was higher than that in pericentral region. In addition, the degree of cytochrome aa3 reduction increased with the distance from the periportal region, reflecting a physiological gradient of oxygen tension along the sinusoidal flow, although with an intersinusoidal heterogeneity within Liver Lobule.
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measurement of redox states of mitochondrial cytochrome aa3 in regions of Liver Lobule by reflectance microspectroscopy
American Journal of Physiology-gastrointestinal and Liver Physiology, 1993Co-Authors: Shengsong Chen, Harumasa Yoshihara, Akitoshi Seiyama, Noboru Harada, Sunao Kawano, Hideyuki Fusamoto, Takenobu Kamada, M Watanabe, H Kosaka, Takeshi ShigaAbstract:To evaluate the sublobular distribution of oxygen tension, the redox states of mitochondrial cytochrome aa3 were assessed in local regions of the Liver Lobule by reflectance microspectroscopy. The reflected light from two focused microspots (20 microns in diam) on the surface of the perfused Liver, placed on the stage of microscope, was conducted to the spectrophotometer with two separate light guides, giving the reflectance spectra. The redox state of cytochrome aa3 was calculated from the difference in reflectance between 603 and 630 nm. The degree of cytochrome reduction increased with the stepwise decline of the influent or effluent oxygen concentrations. The local oxygen concentration in periportal region for the half-maximal reduction of cytochrome aa3 was higher than that in pericentral region. In addition, the degree of cytochrome aa3 reduction increased with the distance from the periportal region, reflecting a physiological gradient of oxygen tension along the sinusoidal flow, although with an i...
Bedii A Salman - One of the best experts on this subject based on the ideXlab platform.
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left sided congenital diaphragmatic hernia associated with intrathoracic ectopic Liver Lobule
European Journal of Cardio-Thoracic Surgery, 2002Co-Authors: Bedii A SalmanAbstract:A case of intrathoracic ectopia of the left lobe lateral segment of the Liver in a patient with left-sided diaphragmatic hernia is described. The ectopic Liver part was found in the left hemithorax during excision of the diaphragmatic hernia sac, but it was not the content of the sac. The ectopic Liver part has not been described previously in the left hemithorax and is actually the primary abnormality. The diaphragmatic hernia is merely a secondary development through this potential gap on the diaphragm where the pedicle of the ectopic Liver Lobule passes.
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case report left sided congenital diaphragmatic hernia associated with intrathoracic ectopic Liver Lobule
2002Co-Authors: Bedii A SalmanAbstract:A case of intrathoracic ectopia of the left lobe lateral segment of the Liver in a patient with left-sided diaphragmatic hernia is described. The ectopic Liver part was found in the left hemithorax during excision of the diaphragmatic hernia sac, but it was not the content of the sac. The ectopic Liver part has not been described previously in the left hemithorax and is actually the primary abnormality. The diaphragmatic hernia is merely a secondary development through this potential gap on the diaphragm where the pedicle of the ectopic Liver Lobule passes. q 2002 Elsevier Science B.V. All rights reserved.
Shengsong Chen - One of the best experts on this subject based on the ideXlab platform.
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ethanol induces heterogeneous reduction of cytochrome aa3 within perfused rat Liver Lobule assessed using microspectroscopy
Alcohol and Alcoholism, 1995Co-Authors: Shengsong Chen, Harumasa Yoshihara, Akitoshi Seiyama, Noboru Harada, Sunao Kawano, Shingo Tsuji, Hideyuki Fusamoto, Takenobu Kamada, Takeshi ShigaAbstract:The redox state of cytochrome aa3 was measured at microspots (20 microns diameter) within the Lobule of perfused rat Livers, using reflectance microspectroscopy, and the effect of ethanol infusion on sublobular distribution of the redox states was evaluated. A sigmoidal relationship was observed between oxygen deLivery and the reduction of cytochrome aa3 in both the periportal and pericentral regions of the Liver Lobule when the influent O2 concentration was decreased in a graduated manner. This sigmoidal curve was shifted to the more reduced state by ethanol infusion, with ethanol (25-100 mM) increasing the degree of cytochrome aa3 reduction in a dose-dependent manner according to the distance from the periportal region along a sinusoid. This increase was spatially heterogeneous within a Liver Lobule. These data indicate that ethanol accelerates cytochrome aa3 reduction, with a distinct gradient of reduction along sinusoids but a heterogeneous distribution within the Liver Lobule.
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measurement of redox states of mitochondrial cytochrome aa3 in regions of Liver Lobule by reflectance microspectroscopy
American Journal of Physiology-gastrointestinal and Liver Physiology, 1993Co-Authors: Shengsong Chen, Harumasa Yoshihara, Akitoshi Seiyama, Noboru Harada, Sunao Kawano, Hideyuki Fusamoto, Takenobu Kamada, M Watanabe, H Kosaka, Takeshi ShigaAbstract:To evaluate the sublobular distribution of oxygen tension, the redox states of mitochondrial cytochrome aa3 were assessed in local regions of the Liver Lobule by reflectance microspectroscopy. The reflected light from two focused microspots (20 microns in diam) on the surface of the perfused Liver, placed on the stage of microscope, was conducted to the spectrophotometer with two separate light guides, giving the reflectance spectra. The redox state of cytochrome aa3 was calculated from the difference in reflectance between 603 and 630 nm. The degree of cytochrome reduction increased with the stepwise decline of the influent or effluent oxygen concentrations. The local oxygen concentration in periportal region for the half-maximal reduction of cytochrome aa3 was higher than that in pericentral region. In addition, the degree of cytochrome aa3 reduction increased with the distance from the periportal region, reflecting a physiological gradient of oxygen tension along the sinusoidal flow, although with an i...
U K Misra - One of the best experts on this subject based on the ideXlab platform.
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chronic ethanol treatment induces h2o2 production selectively in pericentral regions of the Liver Lobule
Alcoholism: Clinical and Experimental Research, 1992Co-Authors: U K Misra, Blair U Bradford, Jeffrey A Handier, Ronald G. ThurmanAbstract:Chronic treatment with ethanol damages pericentral regions of the Liver selectively, and reactive oxygen species such as H2O2 may be involved in the mechanism of hepatotoxicity. To test this idea, the effect of chronic treatment with ethanol on rates of H2O2 production was measured in tissue cylinders isolated from periportal and pericentral regions of Livers from ethanol-treated rats. Rates of hydrogen peroxide production, assessed from the oxidation of methanol to formaldehyde by catalase-H2O2, were similar in tissue cylinders isolated from periportal regions in control and ethanol-treated rats. In contrast, rates of H2O2 production were over 4-fold higher in tissue isolated from pericentral regions of Livers from ethanol-treated than control animals (1.7±0.5 vs. 0.4 ±0.3 nmol/min/mg protein, respectively). Rates of H2O2-generating acyl CoA oxidase activity were equivalent in tissue cylinders from periportal regions of Livers from both groups (approximately 2 nmol/min/mg protein), but were over 2-fold higher in tissue cylinders from pericentral regions of Livers from ethanol-treated rats than from controls. In contrast, catalase activity was increased nearly 2-fold in homogenates from both periportal and pericentral regions by ethanol treatment while glutathione peroxidase activity was decreased significantly in both regions. These data demonstrate that ethanol increases H2O2 generation in pericentral regions of the Liver Lobule in part by elevating rates of peroxisomal β-oxidation of acyl CoA compounds and are consistent with the hypothesis that local increases in H2O2 production may be involved in the mechanism of ethanol-induced hepatotoxicity.
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oxygen tension is a major determinant of hepatotoxicity due to 2 ethylhexanol in isolated tissue cylinders from periportal and pericentral regions of the Liver Lobule from phenobarbital treated rats
Toxicology and Applied Pharmacology, 1991Co-Authors: Decai Liang, U K Misra, Barbara J Keller, Ronald G. ThurmanAbstract:Abstract 2-Ethylhexanol, a metabolite of the commonly used plasticizer di(ethylhexyl)phthalate, was shown to cause toxicity exclusively to periportal regions of the perfused Liver (Keller et al., 1990, J. Pharmacol. Exp. Ther. , 252, 1355–1360.) To determine whether this toxicity was due to local oxygen tension or to drug deLivery, isolated cylinders (plugs) of periportal and pericentral regions of the Liver Lobule from rats pretreated with phenobarbital were collected with a micropunch following brief perfusion of the organ. Plugs were 0.2 mm wide and 0.5 mm long and weighed between 0.5 and 1 mg each. Following incubation for at least 2 hr in Eagle's medium, they were judged viable based on production of urea at high rates and minimal leakage of lactate dehydrogenase (LDH). Plugs could be cultured for up to 24 hr with minimal loss of activity. Urea synthesis from ammonium chloride (3 m m ) by plugs incubated in Krebs-Henseleit buffer equilibrated with 95% O 2 :5% CO 2 was proportional to protein concentration and was linear with time for up to one hour at rates around 75 μmol/g/hr. Icubation of plugs with 2-ethylhexanol (0.1 to 3 m m ) diminished urea synthesis in a dose-related manner (half-maximal effect = 0.5 m m ). Ethylhexanol also caused extensive cell damage assessed from LDH leakage in incubations at 800 μ m O 2 but significantly less injury at 200 μ m O 2 . Concomitantly, urea synthesis was inhibited by ethylhexanol by over 80% at 800 μ m O 2 but less than 50% at 200 μ m O 2 . Plugs isolated from both regions of the Liver Lobule were affected similarly by ethylhexanol and O 2 . Taken together, these data indicate that ethylhexanol toxicity is dependent on oxygen tension in isolated sublobular regions of the Liver Lobule, and therefore it is unlikely that drug deLivery can explain the selective injury to periportal regions in studies with the perfused Liver.
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regulation of urea synthesis in sublobular regions of the Liver Lobule by oxygen
Biochimica et Biophysica Acta, 1990Co-Authors: Yoshiyuki Takei, Frederick C. Kauffman, U K Misra, Hirofumi Yamanaka, Ronald G. ThurmanAbstract:Abstract Periportal and pericentral regions of the Liver Lobule were isolated from perfused rat Liver using a micropunch and incubated in Krebs-Henseleit buffer (pH 7.6) containing 2% poly(ethylene glycol) in Eagle's basal medium, PMSF (50 μg/ml) and leupeptin (20 μg/ml) for 2 h at 25°C under and O 2 /CO 2 (95:5%) gas phase. Maximal rates of urea production from ammonium chloride were 96.4 ± 8.7 and 32.8 ± 5.4 μg per h at 800 and 200 μM O 2 . Thus, urea synthesis was 2ndash;3-times greater at high than low O 2 tension is plugs from periportal and pericentral regions of the Liver Lobule.