Administration Of Lansoprazole Research Articles

Selection of lansoprazole from an FDA-approved drug library to inhibit the Alzheimer's disease seed-dependent formation of tau aggregates.

The efficacy of current treatments is still insufficient for Alzheimer's disease (AD), the most common cause of Dementia. Out of the two pathological hallmarks of AD amyloid-β plaques and neurofibrillary tangles, comprising of tau protein, tau pathology strongly correlates with the symptoms of AD. Previously, screening for inhibitors of tau aggregation that target recombinant tau aggregates have been attempted. Since a recent cryo-EM analysis revealed distinct differences in the folding patterns of heparin-induced recombinant tau filaments and AD tau filaments, this study focused on AD seed-dependent tau aggregation in drug repositioning for AD. We screened 763 compounds from an FDA-approved drug library using an AD seed-induced tau aggregation in SH-SY5Y cell-based assay. In the first screening, 180 compounds were selected, 72 of which were excluded based on the results of lactate dehydrogenase assay. In the third screening with evaluations of soluble and insoluble tau, 38 compounds were selected. In the fourth screening with 3 different AD seeds, 4 compounds, lansoprazole, calcipotriene, desogestrel, and pentamidine isethionate, were selected. After AD seed-induced real-time quaking-induced conversion, lansoprazole was selected as the most suitable drug for repositioning. The intranasal administration of lansoprazole for 4 months to AD seed-injected mice improved locomotor activity and reduced both the amount of insoluble tau and the extent of phosphorylated tau-positive areas. Alanine replacement of the predicted binding site to an AD filament indicated the involvement of Q351, H362, and K369 in lansoprazole and C-shaped tau filaments. These results suggest the potential of lansoprazole as a candidate for drug repositioning to an inhibitor of tau aggregate formation in AD.

Novel Peritoneal Sclerosis Rat Model Developed by Administration of Bleomycin and Lansoprazole.

In our preliminary experiment, peritoneal sclerosis likely induced by peritoneal dialysis was unexpectedly observed in the livers of rats given bleomycin and lansoprazole. We examined whether this peritoneal thickening around the liver was time-dependently induced by administration of both drugs. Male Wistar rats were injected with bleomycin and/or lansoprazole for 2 or 4 weeks. The 3YB-1 cell line derived from rat fibroblasts was treated by bleomycin and/or lansoprazole for 24 h. The administration of both drugs together, but not individually, thickened the peritoneal tissue around the liver. There was accumulation of collagen fibers, macrophages, and eosinophils under mesothelial cells. Expressions of Col1a1, Mcp1 and Mcp3 genes were increased in the peritoneal tissue around the liver and in 3YB-1 cells by the administration of both drugs together, and Opn genes had increased expressions in this tissue and 3YB-1 cells. Mesothelial cells indicated immunoreactivity against both cytokeratin, a mesothelial cell marker, and αSMA, a fibroblast marker, around the livers of rats given both drugs. Administration of both drugs induced the migration of macrophages and eosinophils and induced fibrosis associated with the possible activation of fibroblasts and the possible promotion of the mesothelial-mesenchymal transition. This might become a novel model of peritoneal sclerosis for peritoneal dialysis.

Neuroprotective effect of lansoprazole against cisplatin-induced brain toxicity: Role of Nrf2/ARE and Akt/P53 signaling pathways

Cisplatin is a chemotherapeutic agent usually used in treating different patterns of malignancies. One of the significant apparent complications of cisplatin chemotherapy is brain toxicity. The present study was conducted to evaluate the protective effects of lansoprazole on cisplatin-induced cortical intoxication. Thirty-two rats were allocated into four groups (8 rats/group); group I: received only a vehicle for 10 days, group II: lansoprazole was administered (50 mg/kg) via oral gavage for 10 days, group III: On 5th day of the experiment, rats were given cisplatin (10 mg/kg) i.p. once to induce cortical injury. Group IV: rats were given lansoprazole for 5 days before cisplatin and 5 days afterward. Lansoprazole administration significantly improved cisplatin-induced behavioral changes, as evidenced by decreasing the immobility time in forced swimming and open field tests. Besides, lansoprazole improved cortical histological changes, restored cortical redox balance, enhanced Nrf2/ARE expression, cisplatin-induced neuronal apoptosis, and dampened cisplatin inflammation. In addition, lansoprazole modulated cortical Akt/p53 signal. The present work was the first to show that lansoprazole co-administration reduced cortical toxicity in cisplatin-treated rats via multiple signaling pathways. The current findings provided crucial information for developing novel protective strategies to reduce cisplatin cortical toxicity.

The involvement of Nrf2/HO-1/cytoglobin and Ang-II/NF-κB signals in the cardioprotective mechanism of lansoprazole against cisplatin-induced heart injury

Cardiac toxicity is a serious adverse effect of cisplatin (CIS). Lansoprazole (LPZ) is a proton pump inhibitor with promising cardioprotective effects. Our study planned to examine the cardioprotective effect of LPZ against CIS-induced cardiac injury. To achieve this goal, 32 male rats were randomly allocated into four groups. CIS, 7 mg/kg, was injected i.p. on the fifth day of the experiment. LPZ was administered via oral gavage at a dose of 50 mg/kg. The present study revealed that CIS injection induced a remarkable cardiac injury evidenced by an increase in serum ALP, AST, CK-MB, LDH, and troponin-I levels. The cardiac oxidative damage was also observed after CIS injection and mediated by downregulation of GSH, SOD, GST, Nrf2, HO-1, PPAR-γ, and cytoglobin levels associated with the upregulation of MDA content. Besides, CIS injection caused a significant inflammatory reaction mediated by alteration of cardiac NF-κB, STAT-3, p-STAT-3, and IκB expressions. Additionally, cardiac Ang-II expression was significantly increased in CIS control rats, while Ang 1–7 expression was significantly reduced relative to normal rats. In contrast, LPZ administration remarkably ameliorated these changes in the heart of CIS-intoxicated rats. Collectively, LPZ potently attenuated cardiac toxicity induced by CIS via regulation of Nrf2/HO-1, PPAR-γ, cytoglobin, IκB/NF-κB/STAT-3, and Ang-II/Ang 1–7 signals.

Lansoprazole and zoledronate delays hard tissue healing of tooth extraction sockets in dexamethasone-treated mice.

Proton pump inhibitors (PPIs) are among the most commonly prescribed medicines for the management of acid-related gastrointestinal diseases. Osteonecrosis of the jaw (ONJ) is a serious adverse event that is associated with the use of antiresorptive and antiangiogenic agents. According to previous clinical reports, the use of PPIs contributes to the pathogenesis of severe ONJ that requires surgery. Here, we investigated the effects of lansoprazole (LP) or LP in combination with zoledronate (ZOL) on ONJ development in mice. C57BL/6J mice were administered ZOL (125μg/kg intravenously, twice weekly) and/or LP (10mg/kg intraperitoneally; 3 weeks of 3 consecutive days followed by 1day off). One week after initiation of the study, the first molar was atraumatically extracted. Concurrently with ZOL administration, dexamethasone (Dex) was administered (5mg/kg intraperitoneally, twice weekly). Micro-computed tomography and histological evaluation were performed to characterize femoral structures, tooth extraction sockets, and osteonecrosis areas. The results showed that ZOL/Dex significantly increased bone mass compared to saline/Dex, while the simultaneous administration of LP and ZOL/Dex diminished the ZOL-induced enhancement of bone mass. In the alveolar bone around the tooth extraction socket, necrotic bone was significantly increased in the LP/Dex group compared to the saline/Dex group. However, no signs of more severe ONJ-like lesions were observed following combined administration of LP and ZOL/Dex, other than an increase in the number of non-attached TRAP-positive cells. Our findings in a mouse model suggest that LP use can be a risk factor for the development of ONJ.

Lansoprazole-induced osteoporosis via the IP3R- and SOCE-mediated calcium signaling pathways

BackgroundMany clinical studies have shown a correlation between proton pump inhibitors (PPIs) and osteoporosis or fractures. The purpose of this study was to establish a murine model of chronic oral PPI administration to verify whether PPIs caused bone metabolic impairment and investigate the relevant molecular mechanism underlying the effects of PPIs on MC3T3-E1 murine osteoblasts.MethodsA lansoprazole-induced bone loss model was used to investigate the damaging effects of PPIs. In vivo, immunohistochemistry, Hematoxylin–Eosin (HE) staining, micro-CT analysis, and blood biochemical analyses were used to evaluate the effect of lansoprazole on bone injury in mice. In vitro, the effects of lansoprazole and related signaling pathways in MC3T3-E1 cells were investigated by CCK-8 assays, EdU assays, flow cytometry, laser confocal microscopy, patch clamping, reverse transcription-quantitative polymerase chain reaction and Western blotting.ResultsAfter 6 months of lansoprazole gavage in ICR mice, the micro-CT results showed that compared with that in the vehicle group, the bone mineral density (BMD) in the high-dose group was significantly decreased (P < 0.05), and the bone microarchitecture gradually degraded. Biochemical analysis of bone serum showed that blood calcium and phosphorus were both decreased (P < 0.01). We found that long-term administration of lansoprazole impaired skeletal function in mice. In vitro, we found that lansoprazole (LPZ) could cause calcium overload in MC3T3-E1 cells leading to apoptosis, and 2-APB, an inhibitor of IP3R calcium release channel and SOCE pathway, effectively blocked increase in calcium caused by LPZ, thus protecting cell viability.ConclusionsLongterm administration of LPZ induced osteoporotic symptoms in mice, and LPZ triggered calcium increases in osteoblasts in a concentration-dependent manner. Intracellular calcium ([Ca2+]i) persisted at a high concentration, thereby causing endoplasmic reticulum stress (ERS) and inducing osteoblast apoptosis.

A study for every second day administration of vonoprazan for maintenance treatment of erosive GERD (ESD von GERD): a multicenter randomized cross-over study.

Vonoprazan is a potassium competitive acid blocker used to treat erosive gastroesophageal reflux disease (GERD) with stronger, more stable acid-suppressing effects than proton pump inhibitors (PPIs). This study clarified the usefulness and superiority of vonoprazan administered every second day over PPIs in the maintenance therapy of erosive GERD. This is a prospective, multicenter, open-label, two-period randomized cross-over study. Patients were randomized to either the vonoprazan-lansoprazole (VP-LZ) group, who were given vonoprazan 10mg for the first 4weeks and then lansoprazole 15mg for the next 4weeks both administered once every second day, or the lansoprazole-vonoprazan (LZ-VP) group, who were treated in reverse. GERD symptoms were compared using symptom diaries, the frequency scale for symptoms of GERD (FSSG), and the gastrointestinal symptom rating scale (GSRS). We enrolled 122 patients between December 2017 and May 2019. Symptoms were well controlled in vonoprazan administration and lansoprazole administration were 93.6% and 82.1%, respectively, with a significant difference on McNemar's test (P = 0.003). During the second 4weeks, 94.4% and 76.7% of patients in the VP-LZ and LZ-VP groups, respectively, were well controlled following for ≥ 6 consecutive days a week (P = 0.009). During the first 4weeks, 96.7% and 80.0% of patients were well controlled with < 1 weekly in the VP-LZ and LZ-VP groups, respectively, during the first 4weeks (P = 0.007). GERD symptoms, assessed via FSSG and GSRS, significantly decreased with vonoprazan administration once every second day. Vonoprazan administered once every second day could be an effective alternative to PPIs in the maintenance treatment of erosive GERD (UMIN000030393).

In vitro evaluation of enteral tube administration of lansoprazole orally disintegrating tablets

Lansoprazole orally disintegrating tablets (ODTs) can be administered orally or through a nasogastric (NG) tube for patients who are unable to swallow. In addition, off-label administration through gastrostomy (G) or jejunal (J) tubes has been reported. The purpose of this study was to develop in vitro methods to assess the risk of clogging during administration of two lansoprazole ODTs through enteral feeding tubes. Feeding tubes of various compositions and geometries were selected for testing. Disintegration, sedimentation, percent recovery, acid phase dissolution testing, and particle size distribution measurements were performed. The results indicated that G tubes had the greatest risk of clogging compared to NG and J tubes. In addition, larger particles and an increased amount of insoluble excipients observed in Product B resulted in more irreversible enteral tube clogging than compared to Product A. The geometry and design of the tube also had an impact on the amount of lansoprazole recovered after enteral tube administration. Lansoprazole ODTs demonstrated acid resistance stability regardless of the water used for suspension. The in vitro methods discussed in this work could be used to evaluate in vitro equivalence and to assess the risk of delivering a drug product through an enteral feeding tube.

Lansoprazole a Proton Pump Inhibitor Prevents IBD by Reduction of Oxidative Stress and NO Levels in the Rat

The inflammatory disease's increased prevalence leads to a major concern around the world. Still, there is a lack of effective and successful therapy in the reversal of Inflammatory Bowel Disease (IBD) symptoms. Whereas, reactive oxygen species (ROS) production and muddled defense capacity of antioxidants in IBD subjects reported several times. Many proton pump inhibitors have been reported previously for their anti-inflammatory effect. The present study is aimed to assess the ameliorative effect of lansoprazole in experimentally induced IBD in rats. Thirty-six female Sprague Dawley rats were divided equally into six groups based on their body weight. Lansoprazole (1, 5, and 10 mg/kg, p.o.) and 5-aminosalicylate (5-ASA, 100 mg/kg, p.o.) served as standard control respectively, given for 18 days once a day. On the 11th day of the study, colitis was induced by intrarectal instillation of 2, 4-Dinitrobenzene sulfonic acid (DNBS), and treatment was continued for the next 7 days. Administration of lansoprazole (at 5 and 10 mg/kg) significantly reduced DAI (Disease Activation Index) and CMDI (Colon Macroscopic Damage Index); which further justifies a reduction in colon inflammation grades, as well as histopathological changes, and reflected by the stalling of body weight. The anti-inflammatory effects were indicated by lowered MPO (myeloperoxidase) and SOD (superoxide dismutase) in colon tissue as well as restores colonic NO (nitric oxide) level. The study shows lansoprazole improved DAI and CMDI scores, reduction of neutrophil infiltration, and an improved antioxidant status indicating an anti-ulcerative effect in DNBS-induced experimental colitis that is comparable with 5-ASA treatment.

Effect of renin-angiotensin-aldosterone system blockade on intestinal injury induced by indomethacin in rats

Aim: The aim of this experimental study was to evaluate the possible cytoprotective effects of renin-angiotensin-aldosterone system (RAAS) blockade, captopril (10 mg/kg), telmisartan (10 mg/kg), and a proton-pump inhibitor (lansoprazole) on intestinal injury induced by indomethacin in rats. Materials and Methods: This effect was evaluated through the assessment of intestinal inflammatory biomarkers and oxidative stress parameters. Forty adult male albino rats weighing 170–200 g were used and divided equally into five groups. After the treatment, the following were assessed: Myeloperoxidase (MPO) enzyme activity, pro-inflammatory (interleukin-1beta [IL-1 β]) content and anti-inflammatory (IL-10) content, malondialdehyde (MDA) content, reduced glutathione (GSH) content, and superoxide dismutase (SOD) enzyme activity, and histopathological examination of the intestinal tissues was conducted. Results: Indomethacin group induced a significant increase in MDA content, also in inflammatory biomarker (MPO enzyme activity, IL-1 β content, and IL-10 content) compared to normal control, while indomethacin group induced a significant decrease in GSH content, SOD enzyme activity compared to normal control group. Captopril, telmisartan, lansoprazole administration before indomethacin-induced significant increase in GSH content, SOD enzyme activity, while induced significant decrease in MDA content as well as in inflammatory biomarker compared to indomethacin group, which indicate the antioxidant, anti-inflammatory effects, and the gastroprotective properties of RAAS blockers, which also shown in the histopathological examination of intestinal tissues. Conclusion: This study showed the possible antioxidant and anti-inflammatory effects as well as the gastroprotective properties of RAAS blockers. Telmisartan has more antioxidant and anti-inflammatory effect as well as cytoprotective action than captopril.

S1351 A Study for Every Second Day Administration of Vonoprazan in Maintenance Treatment of Erosive GERD (ESD Von GERD): A Multicenter Randomized Crossover Study

INTRODUCTION: Vonoprazan, a potassium competitive acid blocker, with stronger and more stable acid-suppressing effects than proton pump inhibitors (PPIs), is used to treat erosive gastroesophageal reflux disease (GERD). We clarified the usefulness and superiority of vonoprazan administered every second day over PPIs in maintenance therapy of erosive GERD. METHODS: This was a prospective, multicenter, open-label, two-period randomized crossover study. Patients were randomized to the PCPP group, which was administered vonoprazan 10 mg daily (q.d.) for the first 4 weeks and then lansoprazole 15 mg q.d. the next 4 weeks both administered every second day, and the PPPC group, which was treated in reverse. GERD symptoms including heartburn and acid reflux were compared between vonoprazan and lansoprazole using symptom diaries, frequency scale for symptoms of GERD (FSSG) and gastrointestinal symptom rating scale (GSRS). RESULTS: We enrolled 122 patients between December 2017 and May 2019. Asymptomatic proportion in vonoprazan administration and lansoprazole administration were 93.6% (105/112) and 82.1% (92/112), respectively, and it had a significant difference with analysis using McNemar’s test (P = 0.003). During the first 4 weeks, 93.3% and 85.7% patients were asymptomatic following treatment for ≥6 consecutive days a week in the PCPP and PPPC groups, respectively (P = 0.228), whereas during the second 4 weeks, 94.4% and76.7% patients, respectively were asymptomatic (P = 0.009). Furthermore, 96.7% and 80.0% of patients were asymptomatic with less than once weekly in the PCPP and PPPC groups, respectively, during the first 4 weeks (P = 0.007). GERD symptoms were significantly decreased with vonoprazan administered every second day using FSSG and GERD. CONCLUSION: vonoprazan every second day administration may reduce patient symptoms more effectively than PPIs in erosive GERD maintenance. Furthermore, vonoprazan could be effective maintenance therapies because of their inhibitory effects on gastric acid secretion even when administered every second day and could be selected on-demand. However, further research on long-term administration effects would be necessary.

Concomitant lansoprazole ameliorates cisplatin-induced nephrotoxicity by inhibiting renal organic cation transporter 2 in rats.

Cisplatin is used widely for the treatment of multiple solid tumors. Cisplatin-induced nephrotoxicity is caused by renal accumulation of cisplatin via human organic cation transporter 2 (hOCT2). As lansoprazole, a proton pump inhibitor, is known to inhibit hOCT2 activity, lansoprazole might ameliorate cisplatin-induced nephrotoxicity. A previous study showed that concomitant lansoprazole administration ameliorated nephrotoxicity in patients receiving cisplatin. However, the detailed mechanism remains to be clarified. In the present study, the drug-drug interaction between lansoprazole and cisplatin was examined using hOCT2-expressing cultured cells and rat renal slices. Moreover, the effect of lansoprazole on cisplatin-induced nephrotoxicity and the pharmacokinetics of cisplatin in rats was investigated. In the uptake study, lansoprazole potently inhibited the uptake of cisplatin in hOCT2-expressing cultured cells and rat renal slices. The in vivo rat study showed that concomitant lansoprazole significantly ameliorated cisplatin-induced nephrotoxicity and reduced the renal accumulation of platinum up to approximately 60% of cisplatin alone at 72 h after cisplatin intraperitoneal administration. Furthermore, the renal uptake of platinum at 3 min after intravenous cisplatin administration in rats with cisplatin and lansoprazole decreased to 78% of rats with cisplatin alone. In addition, there was no significant difference in the plasma platinum concentration between rats treated with and without lansoprazole at 3 min after cisplatin intravenous administration. These findings suggested that concomitant lansoprazole ameliorated cisplatin-induced nephrotoxicity by inhibiting rOCT2-mediated cisplatin uptake in rats, thus decreasing cisplatin accumulation in the kidney. The present findings provided important information for the establishment of novel protective approaches to minimize cisplatin-induced nephrotoxicity.

Intravenous esomeprazole versus pantoprazole for heartburn

Heartburn is one of the most common symptoms of gastrointestinal diseases. Intravenous (IV) administration of pantoprazole, lansoprazole, and esomeprazole is recommended by the US Food and Drug Administration (FDA) for short-term acute treatment. Although there are many studies on these drugs in the literature, they are frequently related to long-term oral use and changes in intragastric pH. This study compared the effects of IV esomeprazole with those of IV pantoprazole in patients presenting to the emergency department with heartburn. For this randomized controlled double-blind trial, patients aged over 18 years presenting with gastritis-related heartburn were eligible. Study patients received 40 mg esomeprazole or pantoprazole in 100 ml normal saline. Pain intensity was measured on a visual analog scale (VAS) at 30, 60, and 120 min. Patients were randomized and assigned to either of the two study arms via closed envelopes. Finally, 205 patients were randomized (esomeprazole: 104; pantoprazole 101). Mean age was 39.1 ± 13.78 years and 48.8% were male. Both esomeprazole (median VAS: 26 mm, interquartile range [IQR]: 17–38 mm) and pantoprazole (median: 24 mm, IQR: 14.5–36 mm) effectively reduced heartburn at 30 min, 60 min (median: 59.5 mm, IQR: 48–73.5 mm vs. 55 mm, IQR: 33–68.5 mm), and 120 min (median: 80 mm, IQR: 66.5–89.8 mm vs. 77 mm, IQR: 56–85 mm). While there was no statistically significant difference between the two drugs at 30 min (p = 0.312), there was a statistically significant difference in pain intensity between the esomeprazole and pantoprazole groups at 60 and 120 min (p = 0.014, p = 0.02, respectively). Single-dose slow IV infusion of esomeprazole is faster and more effective in controlling heartburn than pantoprazole.

ADVERSE DRUG REACTION TO ALL PROTON PUMP INHIBITORS EXCEPT ESOMEPRAZOLE IN MEDICALLY COMPLEX PEDIATRIC PATIENT

Introduction Proton-pump inhibitors (PPIs) are commonly used for treatment of gastroesophageal reflux disease (GERD). PPIs have a favourable safety profile; however, immediate and delayed hypersensitivity reactions have been described. Case Description A six-year-old male with hypomyelination with atrophy of the basal ganglia and cerebellum (HABC) and significant medical complexity including seizure disorder, tracheostomy ventilation, severe GERD, and gastro-jejunostomy feeding, developed a papular acneiform eruption 24 hours after administration of omeprazole, lansoprazole, and rabeprazole. The lesions were not evanescent, and did not respond to antihistamine therapy. Skin testing was negative to omeprazole, lansoprazole, rabeprazole, pantoprazole, and esomeprazole. Esomeprazole was started and tolerated well up to 10mg daily, but the patient developed an upper GI bleed due to duodenal ulcer. He was urgently started on pantoprazole infusion. 24 hours later, he developed generalized coalescent erythematous macules, that resolved within 15 minutes of antihistamine administration. Upon discharge, he was continued on pantoprazole with regular antihistamines. Discussion There are three general patterns of hypersensitivity reactions with PPIs: 1) hypersensitivity to one PPI cross-reacting with all other PPIs; 2) cross-reactivity based on structure analogues; and 3) hypersensitivity to single PPI. Other patterns of reactions have been reported; however, tolerance of esomeprazole alone, with clinical reactions to others is uncommon. This was a medically fragile pediatric patient who required PPIs in both acute and chronic settings. This case demonstrates different clinical reactions in the same patient to different PPIs, and the importance of systematically evaluating all PPI options for safe alternatives.

Protocatechuic acid-mediated DJ-1/PARK7 activation followed by PI3K/mTOR signaling pathway activation as a novel mechanism for protection against ketoprofen-induced oxidative damage in the gastrointestinal mucosa

Oxidative stress contributes to the progression of non-steroidal anti-inflammatory drug (NSAID)-induced gastrointestinal (GI) cell apoptosis. In our previous study, we reported that nuclear factor erythroid 2-related factor 2 (Nrf2) plays a protective role against ketoprofen-induced GI mucosal oxidative injury. Recent reports suggest that Nrf2 could exhibit antioxidative and antiapoptosis responses through up-regulation of DJ-1 (PARK7). In the current study, we proposed that induction of DJ-1 expression by protocatechuic acid (PCA) might provide a potential therapeutic approach for treating oxidative stress-associated GI ulcer diseases. The results indicated that PCA increased mRNA expression of glutathione peroxidase and heme oxygenase-1 through up-regulation of DJ-1 followed by Nrf2 translocation. Furthermore, PCA protected Int-407 cells against ketoprofen-induced oxidative stress by regulating the DJ-1, PI3K, and mTOR pathways. Pretreatment with PCA inhibited mitochondrial ROS generation, up-regulated the mitochondrial membrane potential, and down-regulated pro-apoptotic Bax as well as downstream caspase-8, caspase-9, and caspase-3 activity, and reversed impaired DJ-1 and anti-apoptotic Bcl-2 protein expression in Int-407 cells induced by ketoprofen. Similar to the in vitro results, SD rats treated with PCA before administration of ketoprofen exhibited decreased caspase-3 protein expression as well as oxidative damage, and impairment of the antioxidant system and DJ-1 protein expression in the GI mucosa were reversed. The administration of lansoprazole, a type of proton pump inhibitor (PPI), strongly inhibited ketoprofen-induced GI mucosal injuries via up-regulation of DJ-1, indicating that DJ-1 is essential for the dietary antioxidant- and PPI drug-mediated mechanism of ulcer therapy. These results suggest that DJ-1 could be a novel target for protection against ketoprofen-induced GI ulcers due to its antioxidant and anti-apoptosis characteristics.

Lansoprazole prevents the progression of liver fibrosis in non-alcoholic steatohepatitis model rats

We previously demonstrated that lansoprazole provided hepatoprotection in a drug-induced hepatitis animal model partially through the Nrf2/HO-1 pathway. Here, we examined whether lansoprazole could also provide hepatoprotection in a rat model of non-alcoholic steatohepatitis (NASH). Six-week-old rats were fed a normal chow or a choline-deficient amino acid-defined (CDAA) diet to establish a rat model of NASH. The groups fed a CDAA diet for 5 weeks were subcutaneously administered either a vehicle or a lansoprazole suspension for 4 weeks beginning the second week of the experiment. Bridging fibrosis was observed in the livers of almost all the NASH model rats (six of seven), but it was not always observed in NASH model rats (one of seven) continuously administered lansoprazole. The serum aspartate aminotransferase level elevated by the CDAA diet was significantly decreased following lansoprazole administration. Lansoprazole also increased the expression of Nrf2, but not HO-1, in the liver of NASH model rats. Lansoprazole decreased the level of activated TGF-β protein. Furthermore, interleukin-6 gene and protein expression were decreased. Lansoprazole inhibits hepatic fibrogenesis, at least during the early stages, in CDAA diet-induced NASH model rats. The mechanisms might be associated with cytokine suppression but not the inhibition of reactive oxygen species.

Comparison of the early effects of vonoprazan, lansoprazole and famotidine on intragastric pH: a three-way crossover study.

To promote symptom relief from acid-related diseases, a medicine with a rapid-onset effect is ideal. The aim of this study was to investigate the early inhibitory effect on gastric acid secretion after a single oral administration of vonoprazan, which represents a new class of proton pump inhibitors, and to compare this effect with those of lansoprazole and famotidine. Ten Helicobacter pylori (HP)-negative male subjects participated in this randomized, three-way crossover study. A single oral administration of vonoprazan (20 mg), lansoprazole (30 mg) or famotidine (20 mg) was performed, and the intragastric pH was continuously monitored for 6 h. Each drug was administered at least seven days apart. The average intragastric pH during the 6-h period after the administration of famotidine was higher than that after the administration of lansoprazole (median: 4.45 vs 2.65; p = 0.0284). A similar result was observed for vonoprazan and lansoprazole (median: 4.30 vs 2.65; p = 0.0322). In conclusions, oral administration of vonoprazan and famotidine in HP-negative healthy male subjects caused the intragastric pH to rise more quickly than did lansoprazole. (Trial Registration: UMIN000020989)

Lansoprazole-sulfide, pharmacokinetics of this promising anti-tuberculous agent.

Lansoprazole (LPZ) is a commercially available proton-pump inhibitor whose primary metabolite, lansoprazole sulfide (LPZS) was recently reported to have in vitro and in vivo activity against Mycobacterium tuberculosis. It was also reported that a 300 mg kg-1 oral administration of LPZS was necessary to reach therapeutic levels in the lung, with the equivalent human dose being unrealistic. A validated liquid chromatography-tandem mass spectrometric method (LC-MS/MS) for the simultaneous quantification LPZ and LPZS in rat plasma and lung homogenates was developed. We administered 15 mg kg-1 oral doses of LPZ to a healthy rat model to determine the pharmacokinetics of its active metabolite, LPZS, in plasma and lung tissue. We found that the LPZS was present in amounts that were below the limit of quantification. This prompted us to administer the same dose of LPZS to the experimental animals intraperitoneally (i.p.). Using this approach, we found high concentrations of LPZS in plasma and lung, 7841.1 and 9761.2 ng mL-1 , respectively, which were significantly greater than the minimum inhibitory concentration (MIC) for Mycobacterium tuberculosis. While oral and i.p. administration of LPZ resulted in significant concentrations in the lung, it did not undergo sufficient cellular conversion to its anti-TB metabolite. However, when LPZS itself was administered i.p., significant amounts penetrated the tissue. These results have implications for future in vivo studies exploring the potential of LPZS as an anti-TB compound.

The effect of lansoprazole administration during pregnancy on the placenta

The effect of lansoprazole administration during pregnancy on the placenta

A case of collagenous colitis with watery diarrhea improved by ending lansoprazole administration after nutrition support team intervention

A case of collagenous colitis with watery diarrhea improved by ending lansoprazole administration after nutrition support team intervention