omeprazole, Prilosec
Co-purification of gastric mucoproteins with DNA: an explanation for the reported 'interaction' of omeprazole with DNA in rat tissues.

Adams SP, Laws GM, Storer RD, Kraynak AR, DeLuca JG, Nichols WW.

Merck Research Laboratories, West Point, PA 19486.

Recently, Phillips et al. reported that small amounts of radioactivity derived from [14C]omeprazole were 'associated' with DNA purified from gastrointestinal tissues of treated rats (Mutagenesis 7, 277-283, 1992). We hypothesized that this radioactivity arose from omeprazole bound to contaminating protein in the DNA fraction (Mutagenesis 7, 395-396, 1992). Using rats injected with 35S-labeled amino acids, we found significant protein contamination (0.06 microgram of protein per microgram of DNA) in DNA purified from gastrointestinal tissues. Gastric mucous proteins represent likely candidates for binding of omeprazole in the rat model used by Phillips et al. To investigate this, we partially purified proteins from gastric mucus, incubated them with [14C]omeprazole, and then added these radiolabeled mucoproteins to homogenates of rat colon and duodenum before starting the DNA purification. Detectable amounts of the added mucoproteins remained in the DNA fraction, but none of the control protein, bovine serum albumin, remained with the DNA. Further characterization of the mucoproteins by hydroxyapatite chromatography indicated that a certain population of these proteins survived the DNA purification procedures. These data indicate that the association of omeprazole with DNA reported by Phillips et al. most probably is explained by binding of omeprazole to mucous glycoproteins (or other proteins present in the GI tract) that selectively survive DNA purification protocols.

Online source: www.ncbi.nlm.nih.gov/entrez/query.fcgi?cmd=Retrieve&db=PubMed&list_uids=7523925&dopt=Abstract omeprozole Prilosec



omeprazole, Prilosec
Influence of acid and angiogenesis on kinetics of gastric ulcer healing in rats: interaction with indomethacin.

Schmassmann A, Tarnawski A, Peskar BM, Varga L, Flogerzi B, Halter F.

Gastrointestinal Unit, Inselspital, University Hospital, Bern, Switzerland.

Indomethacin delays healing of experimental gastric ulcers. We investigated whether inhibition of gastric acid secretion by omeprazole or stimulation of angiogenesis by basic fibroblast growth factor (bFGF) may reverse this delay. Rats with gastric ulcers induced by cryoprobe were treated subcutaneously with either placebo, indomethacin (2 x 0.5 mg/kg), bFGF (2 x 100 micrograms/kg), omeprazole (1 x 40 mumol/kg), indomethacin plus omeprazole, or indomethacin plus bFGF given daily for 8, 10, 15, and 22 days. Ulcer size, epithelial cell proliferation, angiogenesis, and maturation of granulation tissue were sequentially quantified. Omeprazole significantly accelerated ulcer healing in an early phase (days 3-8). In contrast, bFGF accelerated healing in a late phase (days 10-15). Indomethacin significantly delayed ulcer healing in late phase and decreased prostaglandin generation, cell proliferation, angiogenesis, and maturation of granulation tissue. Despite stimulation of angiogenesis, bFGF did not reverse indomethacin-induced delay in ulcer healing. In contrast, omeprazole reversed indomethacin-induced effects on angiogenesis, cell proliferation, maturation of granulation tissue, and ulcer healing rate.

Online source: www.ncbi.nlm.nih.gov/entrez/query.fcgi?cmd=Retrieve&db=PubMed&list_uids=7532364&dopt=Abstract omeprozole Prilosec



omeprazole, Prilosec
Turnover of the gastric H+,K(+)-adenosine triphosphatase alpha subunit and its effect on inhibition of rat gastric acid secretion.

Gedda K, Scott D, Besancon M, Lorentzon P, Sachs G.

UCLA, USA.

BACKGROUND & AIMS: The rate of turnover and the effect of inhibition of acid secretion on the turnover of gastric H+,K(+)-adenosine triphosphatase (ATPase) is unknown. The aim of this study was to determine the turnover of the alpha subunit of gastric H+,K(+)-ATPase in rats under control conditions and during inhibition of acid secretion by ranitidine or omeprazole. METHODS: The turnover of the alpha subunit of the ATPase was determined by measuring the loss of incorporated 35S-methionine. This was compared with the rate of recovery of K(+)-stimulated ATPase activity in the omeprazole-treated animals. RESULTS: The half-life of the alpha subunit was 54 hours. A 1-week treatment with omeprazole had no significant effect, but the half-life increased to 125 hours (P < 0.01) after continuous ranitidine infusion. After omeprazole treatment, K(+)-stimulated ATPase activity recovered with a half-time of 15 hours. CONCLUSIONS: The turnover of the gastric ATPase subunit was independent of omeprazole inhibition but was prolonged by ranitidine. The effect of ranitidine suggests that the resting pump in tubulovesicles may turn over more slowly than the stimulated pump in the secretory canaliculus. The rapid recovery of ATPase activity compared with turnover after omeprazole is caused by both H+,K(+)-ATPase synthesis and loss of covalently bound drug.

Online source: www.ncbi.nlm.nih.gov/entrez/query.fcgi?cmd=Retrieve&db=PubMed&list_uids=7557078&dopt=Abstract omeprozole Prilosec



omeprazole, Prilosec
Gastroprotective activity of the novel proton pump inhibitor lansoprazole in the rat.

Morini G, Grandi D, Arcari ML, Bertaccini G.

Institute of Pharmacology, University of Parma, Italy.

1. The protective activity of lansoprazole was evaluated on gastric mucosal lesions induced by intragastric 25% NaCl (1 ml/rat for 1 hr) and by indomethacin (20 mg/kg for 6 hr) in the rat and compared with that of omeprazole. 2. Lansoprazole (3, 10 and 10 mumol/kg i.g.) dose-dependently prevented the formation of indomethacin-induced lesions, the inhibition being 99% at the highest dose. Omeprazole, 10 mumol/kg i.g., enhanced the damage by indomethacin while higher doses caused a reduction, lesion index being reduced by 98% at 100 mumol/kg. 3. Histologically in lansoprazole- as well as in omeprazole-pretreated rats, indomethacin-induced necrosis of the mucosa was absent, luminal epithelium being intact. 4. Lansoprazole (30, 100 and 300 mumol/kg) and omeprazole (30, 100 and 300 mumol/kg) dose-dependently reduced the formation of lesions by hypertonic saline. 5. Present results indicated that lansoprazole and omeprazole protect the gastric mucosa in different experimental models of gastric ulceration.

Online source: www.ncbi.nlm.nih.gov/entrez/query.fcgi?cmd=Retrieve&db=PubMed&list_uids=7557244&dopt=Abstract omeprozole Prilosec



omeprazole, Prilosec
Gastric antisecretory activity of lansoprazole in different experimental models: comparison with omeprazole.

Coruzzi G, Adami M, Bertaccini G.

Institute of Pharmacology, University of Parma, Italy.

1. The activity of the novel proton pump with inhibitor lansoprazole was examined in different gastric secretion models in vitro and in vivo, in comparison with omeprazole. 2. In the conscious cat with gastric fistula lansoprazole (0.25-2 mumol/kg i.v.) caused a dose-dependent reduction of the acid secretion induced by dimaprit, pentagastrin, 2-deoxy-D-glucose and bombesin, being approximately as potent as omeprazole (0.25-1.5 mumol/kg i.v.). Similar to omeprazole, lansoprazole was also more effective when administered in hyperacidic states. 3. In the anaesthetized rat with lumen perfused stomach lansoprazole (0.03-1 mumol/kg i.v.) was approximately 3 times more potent than omeprazole (0.1-3 mumol/kg i.v.) in inhibiting the acid secretion induced by histamine, 2-deoxy-D-glucose and forskolin. 4. In the isolated gastric fundus from the immature rat lansoprazole (1-30 microM) reduced basal acid secretion and the acid response to histamine and forskolin, with a potency not significantly different from that of omeprazole. 5. No significant differences were found in the different species between lansoprazole and omeprazole as for the duration of action. 6. In conclusion, lansoprazole exerts a marked antisecretory effect in a variety of gastric secretion models from different species. However, it did not significantly differ from omeprazole when considering either the potency or the duration of action.

Online source: www.ncbi.nlm.nih.gov/entrez/query.fcgi?cmd=Retrieve&db=PubMed&list_uids=7557245&dopt=Abstract omeprozole Prilosec



omeprazole, Prilosec
Effects of omeprazole, famotidine, and ranitidine on the enzyme activities of carbonic anhydrase from bovine stomach in vitro and rat erythrocytes in vivo.

Demir Y, Nadaroglu H, Demir N.

Department of Chemistry, Faculty of Education, Ataturk University, Turkey. DEMIRN Yahoo.com

In this study, the effects of omeprazole, famotidine, and ranitidine on bovine stomach carbonic anhydrase (EC 4.2.1.1.) isoenzymes have been investigated in vitro. Bovine stomach carbonic anhydrase (CA) was purified from four different cell localisations of bovine stomach using affinity chromatography by Sepharose 4B-L-tyrosine sulphanilamide. The inhibition or activation effects of three different medical drugs on CA isoenzymes were determined using esterase activity and the CO(2)-hydratase method by plotting activity % vs. [medical drug]. The K(i) values for omeprazole, famotidine, and ranitidine were determined in all localization CA, respectively. The I(50) values of the drugs exhibiting an inhibition effect were found by means of these graphs. It was observed that omeprazole, famotidine, and ranitidine showed inhibition of bovine stomach CA activity. In addition, in vivo studies were performed for these medical drugs in Sprague-Dawley rats. It was demonstrated that CA in erythrocytes was significantly inhibited by these drugs to 3 h.

Online source: www.ncbi.nlm.nih.gov/entrez/query.fcgi?cmd=Retrieve&db=PubMed&list_uids=15516714&dopt=Abstract omeprozole Prilosec



omeprazole, Prilosec
Effects of long-term omeprazole treatment on adult rat gastric mucosa--enhancement of the epithelial cell proliferation and suppression of its differentiation.

Kakei N, Ichinose M, Tatematsu M, Shimizu M, Oka M, Yahagi N, Matsushima M, Kurokawa K, Yonezawa S, Furihata C, et al.

First Department of Internal Medicine, Faculty of Medicine, University of Tokyo, Japan.

Effects of long-term omeprazole treatment on the process of epithelial cell proliferation and differentiation in the adult rat gastric mucosa were investigated. Animals were treated with omeprazole (25 mg/kg body weight/day) for 28 days to induce anacidity in the stomach. The treatment induced a marked decrease in the number of chief cells in the gastric mucosa and at the same time an increase in that of immature pepsinogen-producing cells expressing class III mucin. This was accompanied by a decrease to 60% and 10% of the control values in the mucosal levels of pepsinogen and its mRNA, respectively. Moreover, the expression of cathepsin E in surface mucous cells was reduced. Cell proliferation studies revealed that the rate of bromodeoxyuridine-labeled cells was increased by omeprazole. The above-described changes were reversed by cessation of the treatment and they were not caused by the omeprazole-treatment at a dose which does not induce anacidity in the stomach. These results suggest that long-term omeprazole treatment reversibly increases the epithelial cell proliferation and suppresses its differentiation in the adult rate gastric mucosa probably by altering the acidic environment specific for the stomach.

Online source: www.ncbi.nlm.nih.gov/entrez/query.fcgi?cmd=Retrieve&db=PubMed&list_uids=7575556&dopt=Abstract omeprozole Prilosec



omeprazole, Prilosec
Effects of tenidap on canine experimental osteoarthritis. I. Morphologic and metalloprotease analysis.

Fernandes JC, Martel-Pelletier J, Otterness IG, Lopez-Anaya A, Mineau F, Tardif G, Pelletier JP.

University of Montreal, Louis-Charles Simard Research Center, Notre-Dame Hospital, Quebec, Canada.

OBJECTIVE. To examine the effects of tenidap and diclofenac on osteoarthritic lesions and metalloprotease activity in experimental osteoarthritis (OA). METHODS. The anterior cruciate ligament of the right stifle joint of 25 mongrel dogs was sectioned by a stab wound. Seven dogs received no treatment, 6 were treated with oral omeprazole (20 mg/day), another 6 were treated with diclofenac (0.25 mg/kg/twice daily) plus omeprazole (20 mg/day), and 6 received oral tenidap (3 mg/kg/twice daily) plus omeprazole (20 mg/day). The dogs received medication for 8 weeks; all dogs were killed at the end of this period. Eight normal dogs were used as controls. Lesions were evaluated macroscopically for the incidence and size of osteophytes and the area and grade of cartilage erosions on the condyles and plateaus, along with histologic evaluation of the severity of the cartilage lesions and synovial inflammation. Stromelysin and collagenase activities and the collagenase messenger RNA (mRNA) level were measured in cartilage and synovial membrane. RESULTS. Compared with the untreated or omeprazole-treated OA groups, the dogs treated with tenidap exhibited significant reduction in the incidence (P < or = 0.001) and size (P < or = 0.0001) of osteophytes. Tenidap also significantly decreased the size and grade of cartilage macroscopic lesions, as well as the histologic severity of cartilage lesions on both condyles and plateaus. The histologic severity of synovial inflammatory reaction was also significantly reduced (P < or = 0.003) in the tenidap group. Tenidap markedly decreased stromelysin and collagenase activity in both cartilage (stromelysin P < or = 0.003; collagenase P < or = 0.01) and synovial membrane (stromelysin P < or = 0.003; collagenase P < or = 0.005). Moreover, tenidap also decreased the collagenase mRNA level in cartilage (P < or = 0.005) and synovial membrane (P < or = 0.002). Diclofenac slightly reduced the incidence and size of osteophytes and cartilage lesions, but these changes were not statistically significant. Diclofenac had no effect on the severity of synovial inflammation, metalloprotease activity, or collagenase expression. CONCLUSION. This study showed that tenidap had a more potent anti-osteoarthritic effect than diclofenac in this model. The effect of the drug in suppressing metalloprotease synthesis, a process known to play a major role in the pathophysiology of osteoarthritic lesions, may explain its mechanism of action.

Online source: www.ncbi.nlm.nih.gov/entrez/query.fcgi?cmd=Retrieve&db=PubMed&list_uids=7575725&dopt=Abstract omeprozole Prilosec