Reactive oxygen species and non-peroxidative mechanisms of cocaine-induced cytotoxicity in rat hepatocyte cultures

Göldlin, Christian; Boelsterli, Urs A.

doi:10.1016/0300-483x(91)90155-t

Cited by 45 publications

(13 citation statements)

References 38 publications

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“…Such variability can arise in the cytochrome P450 isoenzyme concentrations, the relative proportion of each isoenzyme and in the affinity of the drugs to the enzymes involved. Although variability of these factors was shown to be of great importance in humans, 48 it remains to be verified whether it has any significance in rats of the same strain. PBPK models offer the possibility to incorporate interindividual variability of the factors affecting hepatic clearance and metabolic DDIs in order to predict the possible range of these processes for speculative purposes.…”

Section: Discussionmentioning

confidence: 99%

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Extrapolating In vitro Metabolic Interactions to Isolated Perfused Liver: Predictions of Metabolic Interactions between R-Bufuralol, Bunitrolol, and Debrisoquine

Haddad

Poulin²,

Funk

2010

Journal of Pharmaceutical Sciences

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Section: Discussionmentioning

confidence: 99%

“…48 Briefly, the rats were anesthetized with sodium pentobarbital (120 mg/kg, i.p.). The perfusate tubing was inserted via the portal vein, then the v. cava caudalis was cut, and the perfusion was started.…”

Section: Isolation Of Hepatocytesmentioning

confidence: 99%

Extrapolating In vitro Metabolic Interactions to Isolated Perfused Liver: Predictions of Metabolic Interactions between R-Bufuralol, Bunitrolol, and Debrisoquine

Haddad

Poulin²,

Funk

2010

Journal of Pharmaceutical Sciences

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“…Primary rat hepatocytes were obtained by a two‐step liver perfusion, and cells were subsequently seeded in 6‐ or 24‐well plates and left to attach for 3 h, as previously described (17). Medium was then changed to a fatty acid‐free medium (Ham F12 supplemented with 10% BMS), and cells were stimulated in a time‐ and dose‐dependent manner with phytanic acid, palmitic acid, or docosahexaenoic acid (DHA).…”

Section: Methodsmentioning

confidence: 99%

Phytanic acid, a natural peroxisome proliferator‐activated receptor agonist, regulates glucose metabolism in rat primary hepatocytes

et al. 2002

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Phytanic acid, a metabolite of the chlorophyll molecule, is part of the human diet and is present in normal human serum at low micromolar concentrations. It was previously shown to be a ligand of the 9-cis-retinoic acid receptor and peroxisome proliferator-activated receptor (PPAR) a. PPAR agonists are widely used in the treatment of type 2 diabetes. Here, we report that phytanic acid is not only a transactivator of PPARa, but it also acts via PPARb and PPARg in CV-1 cells that have been cotransfected with the respective full-length receptor and an acyl-CoA oxidase-PPAR-responsive element-luciferase construct. We observed that, in contrast to other fatty acids, phytanic acid at physiological concentrations enhances uptake of 2-deoxy-D-glucose in rat primary hepatocytes. This result could be explained by the increase in mRNA expression of glucose transporters-1 and -2 and glucokinase, as determined by quantitative real-time reverse transcriptase-polymerase chain reaction. Compared with the PPARg-specific agonist ciglitazone, phytanic acid exerts only minor effects on the differentiation of C3H10T1/2 cells into mature adipocytes. These results clearly demonstrate that phytanic acid acts via different PPAR isoforms to modulate expression of genes involved in glucose metabolism, thus suggesting a potential role of phytanic acid in the management of insulin resistance.

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“…GSH levels were determined by a fluorimetric assay 27 as described. 28 Briefly, 50-µL aliquots of the supernatants were mixed with 100 µL of o-phthalaldehyde (1 mg/mL methanol) solution in an acryl cuvette, and 1.85 mL of 0.5 mol/L phosphate/5 mmol/L ethylenediaminetetraacetic acid buffer (pH 8) was added. The samples were mixed and left for 15 minutes at room temperature before the fluorescence was recorded with a LS-50 fluorescence spectrometer (Perkin-Elmer Ltd., Beaconsfield, England), using an excitation wavelength of 350 nm and an emission wavelength of 420 nm.…”

Section: Methodsmentioning

confidence: 99%

Acetaminophen hepatotoxicity in tumor necrosis factor/lymphotoxin-α gene knockout mice

et al. 1998

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Recent evidence suggests that macrophages and/or other nonparenchymal cells may release important mediators contributing to the hepatic necrosis induced by high doses of acetaminophen (APAP). The nature and causative role of these mediators has remained elusive, however. To investigate the role of the proinflammatory cytokine, tumor necrosis factor (TNF) in the initiation and early propagation of APAP-induced liver injury, we have used mice deficient in both TNF and the closely related lymphotoxin-␣ (LT-␣). Male TNF/LT-␣ knockout mice and C57BL/6 wild-type mice were treated with a hepatotoxic dose of APAP (400 mg/kg, intraperitoneally), and the development of liver injury was monitored over 8 hours. Both genotypes exhibited similar basal activities of hepatic cytochrome P450 2E1 and 1A2. After APAP administration, both the rate of glutathione consumption and the extent of subsequent selective protein binding did not differ significantly in the knockout and wild-type mice. The TNF/LT-␣-deficient mice developed severe centrilobular necrosis and exhibited highly increased levels of serum alanine aminotransferase and aspartate aminotransferase, the extent of which was not significantly different from that in wild-type mice. In C57BL/6 mice exposed to APAP, no increases in hepatic transcripts of TNF or LT-␣ were found by reverse transcription-polymerase chain reaction, nor was immunoreactive serum TNF detected by enzyme-linked immunosorbent assay over 8 hours posttreatment. These data indicate that, in the absence of the genes encoding for TNF and LT-␣, APAP bioactivation was not altered and mice still developed severe hepatic necrosis. Thus, TNF is unlikely to be a key mediator in the early pathogenesis of APAP-induced hepatotoxicity. (HEPATOLOGY 1998;27:1021-1029.)

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Reactive oxygen species and non-peroxidative mechanisms of cocaine-induced cytotoxicity in rat hepatocyte cultures

Cited by 45 publications

References 38 publications

Extrapolating In vitro Metabolic Interactions to Isolated Perfused Liver: Predictions of Metabolic Interactions between R-Bufuralol, Bunitrolol, and Debrisoquine

Extrapolating In vitro Metabolic Interactions to Isolated Perfused Liver: Predictions of Metabolic Interactions between R-Bufuralol, Bunitrolol, and Debrisoquine

Phytanic acid, a natural peroxisome proliferator‐activated receptor agonist, regulates glucose metabolism in rat primary hepatocytes

Acetaminophen hepatotoxicity in tumor necrosis factor/lymphotoxin-α gene knockout mice

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