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Mark G Clemens - One of the best experts on this subject based on the ideXlab platform.
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effect of α tocopherol on hepatic Mixed Function Oxidases in hepatic ischemia reperfusion
Hepatology, 1992Co-Authors: Mark G ClemensAbstract:This study was done to determine the relationship between microsomal lipid peroxidation during hepatic ischemia/reperfusion and alteration in cytochrome P-450–dependent drug metabolism. Rats were pretreated with α-tocopherol to inhibit lipid peroxidation or with vehicle (soybean oil) and then subjected to 60 min no-flow hepatic ischemia in vivo. Control animals were time-matched sham-ischemic animals. After 1, 5 or 24 hr of reperfusion, liver microsomes were isolated and cytochrome P-450 and Mixed Function Oxidases were studied. In vehicle-treated ischemic rats, serum ALT levels peaked at 5 hr (5,242 ± 682 U/L) and were significantly reduced by α-tocopherol pretreatment (1,854 ± 229 U/L, p < 0.01). Similarly, microsomal lipid peroxidation was elevated in the vehicle-treated ischemic group, but this elevation was prevented by α-tocopherol pretreatment. Microsomal cytochrome P-450 content and aminopyrine-N-demethylase activity were both decreased in vehicle-treated ischemic rats to 60% and 70% of sham-ischemic control levels, respectively. Although α-tocopherol restored cytochrome P-450 content to the level of sham-ischemic control rats, aminopyrine-N-demethylase activity remained at 76% of control with α-tocopherol treatment (p < 0.01 compared with sham-ischemic control). In contrast to what was seen with cytochrome P-450 and aminopyrine-N-demethylase, aniline p-hydroxylase activity was elevated in the vehicle-treated ischemic rats compared with sham-ischemic control rats. These increases were prevented by α-tocopherol pretreatment. Our findings suggest that pretreatment with α-tocopherol reduces hepatocellular damage as indicated by abnormalities in microsomal drug-metabolizing Function during ischemia/reperfusion and that this protection is, in major part, caused by decreased lipid peroxidation. (HEPATOLOGY 1992;15:276–281).
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effect of α tocopherol on hepatic Mixed Function Oxidases in hepatic ischemia reperfusion
Hepatology, 1992Co-Authors: Sunmee Lee, Mark G ClemensAbstract:This study was done to determine the relationship between microsomal lipid peroxidation during hepatic ischemia/reperfusion and alteration in cytochrome P-450-dependent drug metabolism. Rats were pretreated with alpha-tocopherol to inhibit lipid peroxidation or with vehicle (soybean oil) and then subjected to 60 min no-flow hepatic ischemia in vivo. Control animals were time-matched sham-ischemic animals. After 1, 5 or 24 hr of reperfusion, liver microsomes were isolated and cytochrome P-450 and Mixed Function Oxidases were studied. In vehicle-treated ischemic rats, serum ALT levels peaked at 5 hr (5,242 +/- 682 U/L) and were significantly reduced by alpha-tocopherol pretreatment (1,854 +/- 229 U/L, p less than 0.01). Similarly, microsomal lipid peroxidation was elevated in the vehicle-treated ischemic group, but this elevation was prevented by alpha-tocopherol pretreatment. Microsomal cytochrome P-450 content and aminopyrine-N-demethylase activity were both decreased in vehicle-treated ischemic rats to 60% and 70% of sham-ischemic control levels, respectively. Although alpha-tocopherol restored cytochrome P-450 content to the level of sham-ischemic control rats, aminopyrine-N-demethylase activity remained at 76% of control with alpha-tocopherol treatment (p less than 0.01 compared with sham-ischemic control). In contrast to what was seen with cytochrome P-450 and aminopyrine-N-demethylase, aniline p-hydroxylase activity was elevated in the vehicle-treated ischemic rats compared with sham-ischemic control rats. These increases were prevented by alpha-tocopherol pretreatment.(ABSTRACT TRUNCATED AT 250 WORDS)
L. Shutt - One of the best experts on this subject based on the ideXlab platform.
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polychlorinated biphenyl pcb effects on hepatic Mixed Function Oxidases and porphyria in birds ii american kestrel
Comparative Biochemistry and Physiology Part C: Comparative Pharmacology, 1991Co-Authors: J E Elliott, S W Kennedy, D Jeffrey, L. ShuttAbstract:1. In order to study the effects of polychlorinated biphenyls (PCBs) on American kestrels (Falco sparverius), groups of 6 female birds were fed toxic equivalent doses, estimated from rat studies, of either 2,3,3′4,4′-PCB (3 mg/kg/day) or 3,3′,4,4′,5-PCB (0.05 mg/kg/day) and a comparable dose of 2,2′,4,4′,5,5′-HxCB (4 mg/kg/day) for 4 weeks. 2. Livers were assayed for ethoxyresorufin O-deethylase (EROD), aminopyrine N-demethylase (APND) and aldrin epoxidase (AE) activity and also analyzed for concentrations of porphyrins by HPLC; abdominal fat was analyzed for residues of PCB congeners by GC/ECD. 3. Chronic dosing with 3,3′,4,4′,5-PCB (congener 126) caused significant induction of hepatic EROD and AE; dosing with 2,3,3′4,4′-PCB (congener 105) caused significant hepatic APND induction; dosing with 2,2′,4,4′,5,5′-HxCB (congener 153) caused significant induction of APND and AE. 4. None of the congeners had a significant effect on mean liver weight or mean hepatic porphyrin levels. 5. The data indicate that the relative response of kestrels to dosing with PCB congeners is different from both quail and rats.
Michio Yamaguchi - One of the best experts on this subject based on the ideXlab platform.
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liver microsomal Mixed Function Oxidases in response to dietary n 3 fatty acid levels in rats
Annals of Nutrition and Metabolism, 1994Co-Authors: Morio Saito, Michio YamaguchiAbstract:Phenobarbital (PB)-induced activities of the liver microsomal Mixed-Function oxidase (MFO) system in response to dietary levels of n-3 fatty acids were investigated in rats. The MFO activities were as
J E Elliott - One of the best experts on this subject based on the ideXlab platform.
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polychlorinated biphenyl pcb effects on hepatic Mixed Function Oxidases and porphyria in birds ii american kestrel
Comparative Biochemistry and Physiology Part C: Comparative Pharmacology, 1991Co-Authors: J E Elliott, S W Kennedy, D Jeffrey, L. ShuttAbstract:1. In order to study the effects of polychlorinated biphenyls (PCBs) on American kestrels (Falco sparverius), groups of 6 female birds were fed toxic equivalent doses, estimated from rat studies, of either 2,3,3′4,4′-PCB (3 mg/kg/day) or 3,3′,4,4′,5-PCB (0.05 mg/kg/day) and a comparable dose of 2,2′,4,4′,5,5′-HxCB (4 mg/kg/day) for 4 weeks. 2. Livers were assayed for ethoxyresorufin O-deethylase (EROD), aminopyrine N-demethylase (APND) and aldrin epoxidase (AE) activity and also analyzed for concentrations of porphyrins by HPLC; abdominal fat was analyzed for residues of PCB congeners by GC/ECD. 3. Chronic dosing with 3,3′,4,4′,5-PCB (congener 126) caused significant induction of hepatic EROD and AE; dosing with 2,3,3′4,4′-PCB (congener 105) caused significant hepatic APND induction; dosing with 2,2′,4,4′,5,5′-HxCB (congener 153) caused significant induction of APND and AE. 4. None of the congeners had a significant effect on mean liver weight or mean hepatic porphyrin levels. 5. The data indicate that the relative response of kestrels to dosing with PCB congeners is different from both quail and rats.
Laurence Chauvelotmoachon - One of the best experts on this subject based on the ideXlab platform.
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effects of interleukin 6 on cytochrome p450 dependent Mixed Function Oxidases in the rat
Biochemical Pharmacology, 1992Co-Authors: Y. L. Chen, I Florentin, Luc Ferrari, Anne-marie Batt, Jean Paul Giroud, Laurence ChauvelotmoachonAbstract:Abstract Intravenous treatment of male rats with recombinant human interleukin-6 (rhIL6) at 50, 100 and 200μg/kg (corresponding to 4, 8 and 16 × 104 U/animal, respectively) reduced the activities of hepatic microsomal cytochrome P450-dependent monoxygenases to varying degrees. Ethylmorphine-N-demethylase/ activity fell to 53% of control values, an effect similar to that induced by 2.5 μg/kg Escherichia coli lipopolysaccharide (LPS). Ethoxycoumarin-O-deethylase activity was also sensitive to inhibition, whereas IL6 had little effect on the activities of other P450-dependent enzymes, including ethoxyresorufin-O-deethylase. Pentoxyresorufin dealkylase activity, which is representative of the cytochrome P450 IIB 1 2 subfamily, was unaffected by IL6 whereas LPS reduced it to 33.7% of control values. Another hepatocyte-related parameter, serum concentration of α1-acid glycoprotein (AGP), was increased by up to 3.5-fold over baseline by IL6 and 10-fold by LPS. Recombinant human interleukin-1β (rhIL1β) 10μg/kg, corresponding to 5 × 104U/rat) and recombinant human tumor necrosis factor α (rhTNF) (150 μg/kg corresponding to 24 × 104U/rat) were both as potent as LPS (2.5 μg/kg) in increasing serum AGP levels and reducing hepatic microsomal monoxygenase activities. IL6 did not potentiate the effects of rhIL1β. Hepatic microsomal glucuronyltransferase activities were little affected by LPS and unaffected by rhIL6. Finally, rhIL6 was more potent after i.p. injection than after i.v. or s.c. injection. These results suggest that the effects of LPS, TNF and IL1 on the Mixed Function oxidase system in vivo may be due partly to an induction of IL6 in vivo. The different sensitivities of the enzymes to IL6 but not to IL1 or TNF may be due to the involvement of two distinct mechanisms.