The mechanism of the inhibitory effect of dithiocarbamates and carbon disulfide on the lipid-peroxidation of the rat liver microsomes

1985 ◽  
Vol 1 ◽  
pp. S73
Keyword(s):  
Lipid Peroxidation ◽  
Rat Liver ◽  
Carbon Disulfide ◽  
Liver Microsomes ◽  
Inhibitory Effect ◽  
Rat Liver Microsomes

Autoregulation of 3, 3′,5′-triiodothyronine production by rat liver microsomes

1981 ◽  
Vol 98 (2) ◽  
pp. 240-245 ◽  
Author(s):  
T. Kaminski ◽  
J. Köhrle ◽  
R. Ködding ◽  
R.-D. Hesch
Keyword(s):  
Rat Liver ◽  
Incubation Medium ◽  
Liver Microsomes ◽  
Inhibitory Effect ◽  
Incubation Mixture ◽  
Rat Liver Microsomes ◽  
Experimental Conditions ◽  
Physiological Concentration ◽  
Enzyme Binding ◽  
Ph Dependent

Abstract. Conversion of thyroxine (T4) to 3,3′,5′-triiodothyronine (rT3) was studied in rat liver microsomes. Addition of rT3 at a physiological concentration to the incubation medium inhibited the deiodination of thyroxine to rT3. With a concentration of rT3 greater than 37.6 nM no net rT3 production at pH 8.0 was observed. Further increases in rT3 concentration resulted only in degradation of added rT3 and no net synthesis of rT3 from T4 could be detected. The inhibitory effect of rT3 upon its own production from T4 was pH dependent, 5 fold lower amounts of hormone being required to inhibit completely rT3 production at pH 7.4 than at pH 8.0. With the same experimental conditions no significant effect of rT3 on the conversion of T4 to 3,5,3′-triiodothyronine (T3) could be observed at pH 8.0 with all concentrations of added iodothyronine. A linear production of 3,3′-T2 from added rT3 was determined over the whole range of rT3 concentration, suggesting a lack of saturation of deiodinating enzyme. Binding of rT3 by anti-rT3 antibody added to the incubation mixture enhanced rT3 production from T4 by protecting rT3 from being degraded and/or diminishing the inhibitory effect of this iodothyronine on its own production. It was concluded that rT3 influenced its own production and that this effect may represent an important autoregulatory process in the iodothyronine metabolism.

Inhibitory Effect of Resveratrol on the Pharmacokinetics of Ticagrelor in Vivo and Vitro

2021 ◽  
Author(s):  
Peng Wang ◽  
Xiao-Xia Hu ◽  
Ying-hui Li ◽  
Nan-Yong Gao ◽  
Guo-quan Chen ◽  
...  
Keyword(s):  
Rat Liver ◽  
Liver Microsomes ◽  
In Vitro Study ◽  
Inhibitory Effect ◽  
Control Group ◽  
Rat Liver Microsomes ◽  
Sprague Dawley ◽  
Group B

This study was to evaluate the effect of resveratrol on the pharmacokinetics of ticagrelor in rats and the metabolism of ticagrelor in human CYP3A4 and liver microsomes. Eighteen Sprague-Dawley rats were randomly divided into three groups: group A (control group), group B (50mg/kg resveratrol), and group C (150mg/kg resveratrol ). After 30 minutes administration of resveratrol, a single dose of ticagrelor (18mg/kg) was administered orally. The vitro experiment was performed to examine the influence of resveratrol on ticagrelor metabolism in CYP3A4*1, human, and rat liver microsomes. Serial biological samples were assayed by validated UHPLC-MS/MS methods. In vivo study, the AUC and Cmax of ticagrelor in group B and C appeared to be significantly higher than the control group, while Vz/F and CLz/F of ticagrelor in group B and C were significantly decreased. In vitro study, resveratrol exhibited an inhibitory effect on CYP3A4*1, human and rat liver microsomes. The IC50 values of resveratrol were 56.75μM，69.07μM and 14.22μM, respectively. Our results indicated that resveratrol had a inhibitory effect on the metabolism of ticagrelor in vitro and vivo. It should be paid more attention to the clinical combination of resveratrol with ticagrelor and ticagrelor plasma concentration should be monitored to avoid the occurrence of adverse reaction.

Lipid Peroxidation and Cherniluminescence during Naproxen Metabolism in Rat Liver Microsomes

1994 ◽  
Vol 13 (12) ◽  
pp. 831-838 ◽  
Author(s):  
Hiroyuki Yokoyama ◽  
Toshiharu Horie ◽  
Shoji Awazu
Keyword(s):  
Lipid Peroxidation ◽  
Singlet Oxygen ◽  
Rat Liver ◽  
Liver Microsomes ◽  
Thiobarbituric Acid ◽  
Rat Liver Microsomes ◽  
Oxygen Species ◽  
Thiobarbituric Acid Reactive Substances ◽  
Microsomal Suspension ◽  
Weight Protein

1 Rat liver microsomal suspension containing NADPH and MgCl2 was incubated at 37°C with naproxen, a non-steroidal anti-inflammatory drug. Thiobarbituric acid reactive substances (TBA-RS), high molecular weight protein aggregates and fluorescent substances were formed in the microsomal suspension. 2 Chemiluminescence was produced from the microsomal suspension. This chemiluminescence production was well correlated to the TBA-RS formation, indicating that the chemiluminescence production was closely associated with the lipid peroxidation. 3 The addition of SKF-525A to the microsomal suspension inhibited the production of TBA-RS, chemiluminescence and 6-demethylnaproxen (6-DMN), the oxidative product of naproxen. Further, the antioxidant, α-tocopherol and singlet oxygen quenchers like histidine, dimethylfuran and 1,4-diazabicyclo[2,2,2]octane strikingly inhibited the productions of chemiluminescence and TBA-RS. 4 Neither naproxen nor 6-DMN caused lipid peroxidation in the absence of NADPH. Thus, lipid peroxidation and chemiluminescence during the oxidation of naproxen in liver microsomes was suggested to be provoked by reactive oxygen species and an origin of chemiluminescence was shown to be singlet oxygen.

scholarly journals The stimulatory effects of asbestos on NADPH-dependent lipid peroxidation in rat liver microsomes

1987 ◽  
Vol 241 (2) ◽  
pp. 561-565 ◽  
Author(s):  
M Fontecave ◽  
D Mansuy ◽  
M Jaouen ◽  
H Pezerat
Keyword(s):  
Lipid Peroxidation ◽  
Rat Liver ◽  
Active Sites ◽  
Oxygen Radicals ◽  
Liver Microsomes ◽  
Rat Liver Microsomes ◽  
Iron Ions ◽  
Ferrous Ions ◽  
Solid Iron ◽  
Ferric Oxides

Lipid peroxidation in rat liver microsomes induced by asbestos fibres, crocidolite and chrysotile, is greatly increased in the presence of NADPH, leading to malondialdehyde levels comparable with those induced by CCl4, a very strong inducer of lipid peroxidation. This synergic effect only occurs during the first minutes and could be explained by an increase or a regeneration of the ferrous active sites of asbestos by NADPH, which in turn could rapidly be prevented by the adsorption of microsomal proteins on the surface of the fibres. It is not inhibited by superoxide dismutase, catalase and mannitol, indicating that oxygen radicals are not involved in the reaction. It is also not inhibited by desferrioxamine, indicating that it is not due to a release of free iron ions in solution from the fibres. Lipid peroxidation in NADPH-supplemented microsomes is also greatly increased upon addition of magnetite. This could be linked to the presence of ferrous ions in this solid iron oxide, since the ferric oxides haematite and goethite are completely inactive.

Inhibitory effect of curcumin on fatty acid desaturation inMortierella alpina 1S-4 and rat liver microsomes

Lipids ◽  
1992 ◽  
Vol 27 (7) ◽  
pp. 509-512 ◽  
Author(s):  
Sakayu Shimizu ◽  
Saeree Jareonkitmongkol ◽  
Hiroshi Kawashima ◽  
Kengo Akimoto ◽  
Hideaki Yamada
Keyword(s):  
Fatty Acid ◽  
Rat Liver ◽  
Liver Microsomes ◽  
Inhibitory Effect ◽  
Fatty Acid Desaturation ◽  
Rat Liver Microsomes
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