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In the present study, the induction of drug-metabolizing enzymes and transporters was evaluated by analyzing mRNA expression in human hepatocytes after exposure to various compounds. The compounds tested included typical enzyme inducers, rifampicin and omeprazole, and controls. All experiments were performed in the presence of 0.1% DMSO. Analysis was performed by the real-time reverse-transcription polymerase chain reaction method (RT-PCR) in the presence of TaqMan probes using an ABI PRISM 7700 Sequence Detector system. A new analytic method to quantify mRNA levels in small numbers of human hepatocytes has been developed for phase I enzymes, phase II enzymes, and transporters. The levels of CYP1A1, CYP2B6, CYP2C8, CYP3A4, CYP3A5, ADH3, and ABCG1 mRNA in human hepatocytes increased after exposure to rifampicin. The levels of CYP1A1, CYP2B6, CYP3A4, CYP3A5, and ABCG1 mRNA recovered after a change to media without rifampicin. The levels of CYP1A1, CYP1A2, CYP1B1, ALDH3, and ALDH6 mRNA increased after exposure to omeprazole, and recovered after a change to media without omeprazole. On the other hand, the levels of ADH3 and ABCB4 mRNA decreased after exposure to omeprazole, and recovered after a change to media without omeprazole. In conclusion, these results demonstrate the applicability of quantitative real-time RT-PCR to the evaluation of the gene induction and recovery of drug-metabolizing enzymes and transporters after exposure to drugs in human hepatocytes.
online pharmacy ref source: www.ncbi.nlm.nih.gov/entrez/query.fcgi?cmd=Retrieve&db=PubMed&list_uids=12040753&dopt=Abstract
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Eksp Klin Gastroenterol. 2002;(2):29-31, 101.
[The gastric mucigenous function in the treatment of patients with ulcer with various antisecretory preparations]
[Article in Russian]
Vakhrushev IaM, Muravtseva OV.
State Medical Academy, Department of Propedeutics of Internal Diseases, Izhevsk.
The investigation of the gastric mucigenous function in dynamics in the treatment by antisecretory medications was carried out in 120 patients with peptic ulcer disease. The selective Mi-cholinolytic gastrocepine, H2-blockers--Ranitidin and Famotidin, the proton pump inhibitor--Omeprasol, were used in the complex therapy. The mucigenous stomach function was investigated by the biochemical method at the level of sialic acids fractions, glycoproteins, glycosaminoglycans and proteins. It was shown that at the exacerbation of the ulcerative disease the expressed changes in gastric mucus were observed. It was shown, that Mi-cholinolytic gastrocepine has the most effective recovering activity on the gastric mucigenous function. The obtained results expand the possibilities of differential use of antisecretory preparations in ulcerative disease in connection with the gastric mucigenous function and acidity disorders.
online pharmacy ref source: www.ncbi.nlm.nih.gov/entrez/query.fcgi?cmd=Retrieve&db=PubMed&list_uids=12046381&dopt=Abstract
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Epilepsy Res. 2001 Jul;46(1):85-9.
Anticonvulsant activity of omeprazole in rats.
Balakrishnan S, Bhargava VK, Pandhi P.
Department of Pharmacology, Postgraduate Institute of Medical Education and Research, Chandigarh 160012, India.
Omeprazole has long been used as an effective agent to treat peptic ulcer. Recent studies have shown that in addition to inhibiting the H(+)-K(+)ATPase, it also inhibits carbonic anhydrase (CA) types I, II and IV. This led us to investigate its anticonvulsant effect in a rat model of electroconvulsion. Since other carbonic anhydrase inhibitors like acetazolamide induce tolerance upon repeated use, we tested the tolerance potential of omeprazole upon repeated administration of up to 1 week. The animals were divided into four groups receiving normal saline, omeprazole 0.5, 1 or 2 mg/kg intraperitoneally. CC(50), i.e. the threshold current inducing tonic hind limb extension in 50% of the rats was established using a technoconvulsometer which delivers currents of varying intensity via ear clip electrodes. The CC(50) was established 30 min after injection of omeprazole. In another group of rats, omeprazole 2 mg/kg was given for 6 days and the CC(50) determined on days 0, 1, 3 and 6. Also the concentration of omeprazole in the brain was determined using high performance liquid chromatography. The CC(50) in vehicle-treated rats was 98 mA, which increased to 126, 135 and 162 mA with 0.5, 1 and 2 mg/kg of omeprazole, respectively. On repeat-dose studies the CC(50) on day 0 was 96 mA, on day 1 166 mA, on day 3 129 mA and on day 6 102 mA. The average brain concentration of omeprazole was 53.2+/-6.9 ng/g of brain tissue. In conclusion, this study has shown omeprazole to be an effective anticonvulsant, but rapidly develops tolerance to its anticonvulsant action. This study can stimulate interest in the development of agents with dual function -- inhibition of CA as well as the accompanying Na(+)-K(+) ATPase -- and such agents may prove to be effective anticonvulsants without exhibiting tolerance.
online pharmacy ref source: www.ncbi.nlm.nih.gov/entrez/query.fcgi?cmd=Retrieve&db=PubMed&list_uids=11395292&dopt=Abstract
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