Effects of high fat diet on kidney lipid content and the Na, K-ATPase activity

ABSTRACT It is widely known that high fat diet (HFD) can contribute to the advent of health problems. Recent studies have indicated that obesity imposes a hemodynamic overload to the kidneys. In order to further investigate such injuries, two groups of six Swiss mice each were fed with a controlled AIN93G diet or a high fat (AIN93G modified) diet for eight weeks. Blood samples were collected to determine the hormonal, lipid profile, glucose, urea, and creatinine levels. Histopathological and immunohistochemical analysis were carried out to analysis the kidney damage. Fractions of renal membranes were prepared to assess the Na,K-ATPase activity, lipid peroxidation, total cholesterol, and phospholipid content. The results indicated that the blood lipid profile, urea and creatinine was not altered by the HFD. On the other hand, it was observed in HFD diet mice elevated glucose blood levels along with an augment on insulin and a decrease on corticosterone release. HFD provoked a reduction in the diameter of the convoluted tubules and cell volume in Bowman's capsule and an increased number of positive cells with Na,K-ATPase, but reduced the Na,K-ATPase activity and the cholesterol content in the kidney cell membrane but favored the lipid peroxidation.

Study on activities and protein and gene expression of renal H(+)-K(+)-ATPase in rats subchronic exposed to trimethyltin chloride / 中华劳动卫生职业病杂志

<p><b>OBJECTIVE</b>To study the activity, protein and gene expression of renal HK-ATPase (HKA) in rats subchronic exposed to trimethyltin chloride (TMT).</p><p><b>METHODS</b>In subchronic toxic test (14-week), 55 female SD rats (age, 6 weeks) were divided randomly into 5 groups: control, low, medium, high and super high dosage, respectively, which drank water with TMT of 0, 8.20, 32.81, 131.25 and 262.50 microg x kg(-1) x d(-1) for 14 weeks. Then serum K+ levels were measured; the activities of HK-ATPase (HKA) in kidneys were detected by the method of determinated phosphorus content; Western Blot assay and real-time PCR were used to exam the protein and mRNA expression levels of HKA in kidneys, respectively.</p><p><b>RESULTS</b>The serum K+ level in super-high dosage group was (5.6 +/- 0.4) mmol/L, which was significantly lower than that [(6.9 +/- 0.3) mmol/L] in control group (P < 0.01). The HKA enzymatic activity of kidneys in low and super high dosage groups was 4.50 +/- 1.45 and 4.55 +/- 0.72 micromolPi x mg prot(-1)h(-1), respectively, which were significantly lower than that (6.55 +/- 0.77 micromol Pi x mg prot(-1) h(-1)) in control group (P < 0.05).</p><p><b>CONCLUSION</b>When rats were exposed subchronic to TMT, the renal HKA activity could reduce, but the expression levels of HKA protein and mRNA did not decrease.</p>

Anti-ulcer & antioxidant activities of Hedranthera barteri {(Hook F.) Pichon} with possible involvement of H+, K+ ATPase inhibitory activity.

Background & objective: Hedranthera barteri (HB) is used in folk medicine as a vermifuge, laxative and an anti-inflammatory agent. The aim of this study was to evaluate the anti-ulcer and antioxidant properties of the dichloromethane fraction of HB root (DMHBR). Methods: Anti-ulcerogenic activity was assessed in cold-restraint (CRU), aspirin (ASP), alcohol (AL), pyloric ligation (PL) induced gastric ulcer models in rats and histamine-induced duodenal ulcer (HST) in guinea pigs. The effect of DMHBR (100 mg/kg) on gastric juice for free and total acidity, peptic activity and mucin secretion, using the pylorus ligated model, were evaluated. The H+, K+-ATPase activity was assayed in gastric microsomes, spectrophotometrically. The in vitro anti-oxidant assays were explored through DPPH, nitric oxide, hydroxyl radical, superoxide anion scavenging assays. Results: DMHBR reduced the incidence of ulcers in CRU (63.3%), PL (58.5%), ASP (52.7%), HST (75.0%) and AL (53.87%). Also, reductions were observed in the free acidity (49.4%), total acidity (45.8%) and peptic activity (32.9%) with increase in the mucin secretion by 81.6 per cent. DMHBR (60-100 μg/ml) inhibited the H+,K+-ATPase activity with IC50 of 89.64 μg/ml compared with omeprazole (10-50 μg/ml ) with IC50 of 32.26 μg/ml. DMHBR showed antioxidant activity with IC50 values of DPPH (397.69 μg/ml), nitric oxide (475.88 μg/ml), hydroxyl radical (244.22 μg/ml) and superoxide anion radical (285.20 μg/ml). Interpretation & conclusion: DMHBR showed anti-ulcer activity against experimentally-induced peptic ulcer models and exhibited both cytoprotective and anti-secretory property. It exhibited a proton pump inhibition activity and its anti-ulcer properties may be partly ascribed to its antioxidant activities.

Gastric atrophy and intestinal metaplasia in a patient on long-term proton pump inhibitor therapy.

We report the case of a patient with gastroesophageal reflux disease who developed gastric atrophy and intestinal metaplasia (IM) while on 20-year treatment with proton pump inhibitors. This is perhaps the first report in human beings. A 74-year-old man, who presented with heartburn, showed abnormally high gastric pH (average 6.57) on 24-hour dual channel pH-metry even after discontinuing acid suppressive drugs for one month. No significant esophageal acid exposure was noted, which may be related to an impairment of the acid secreting capacity of the stomach (percentage time esophageal pH<4 during 24-h period 0.3%). Upper gastrointestinal endoscopy was normal except for the prominent submucosal vessels in the body and fundus suggesting gastric atrophy. Histopathological examination of multiple biopsies from the body and antrum of stomach showed signs of gastric atrophy and IM. Rapid urease test and histopathology of gastric biopsies were negative for Helicobacter pylori. Anti-H.pylori IgG ELISA however, was positive. Patient was asked to stop all anti-secretory drugs and only prokinetics were prescribed following which his symptoms markedly improved. On follow-up, in April 2007, he developed symptoms of peripheral neuropathy; serum vitamin 812 level was low. He responded to parenteral vitamin 812 therapy. 24-h dual channel pH-metry repeated after one and a half years showed persistently high gastric pH (average pH 6.76). The patient remained well after discontinuing proton pump inhibitors and continuing prokinetics and vitamin B12 injections.

Effect of Aqueous Extract of Alstonia Congensis on Glucose Transport and Na+-K+-ATPase Activity in the Everted and Non-Everted Guinea Pig Intestine and Erythrocyte Fragility

The seed of Alstonia congensis has been used as purgative by traditional doctors. It is not known if glucose transport and Na+-K+ ATPase activity are affected during the purging process. The effect of the plant on erythrocytes fragility is also not known. This study was designed to provide this information. The effect of aqueous extract (1:25w/v) of Alstonia congensis on the transportation of glucose ranging from 0.10 to 0.40M from normal and everted guinea pig intestinal strips into the surrounding 0.5M TrisEDTA saline buffer pH 8.2; on Na+-K+- ATPase activity and erythrocytes fragility were measured. Results showed that the aqueous extract reduced glucose transportation; inhibited Na+-k+-ATPase activity and specific activity at higher enzyme protein concentration and activated the enzyme activity and specific activity at lower enzyme protein concentration. Glucose transport reduction was linked to the effect of the extract on the Na+-k+-ATPase system. The extract also increased erythrocytes fragility. The active ingredient(s) in the extract is not known yet and research work is in progress to ascertain it

Selective COX-2 inhibitor delays experimental gastric ulcer healing by stimulating gastric acid secretion in rats / 南方医科大学学报

<p><b>OBJECTIVE</b>To observe the effect of selective cyclooxygenase-2 (COX-2) inhibitor on the healing of experimental gastric ulcer in rats and explore its mechanisms in light of gastric acid secretion.</p><p><b>METHODS</b>Gastric ulcers were induced in rats by an application of acetic acid to the serosal surface of the anterior gastric body. The effects of selective COX-2 inhibitor, celecoxib, on the healing of gastric ulcer, the total acidity of gastric juice, the expressions of H+, K+-ATPase mRNA and protein, and the ultrastructure of the parietal cell were observed in comparison with the effects of normal saline.</p><p><b>RESULTS</b>Nine days after ulcer induction, the ulcer area was 11.9-/+3.1 mm square and 19.7-/+3.8 mm square in rats with normal saline and celecoxib treatments, respectively (P<0.01). The total acidity of gastric juice and the expressions of H+, K+-ATPase mRNA and protein in celecoxib group were significantly higher than that in normal saline group at both 6 and 9 days after ulcer induction, but no significant difference was found between the two groups in the amount of secretary canaliculus and microvillus.</p><p><b>CONCLUSION</b>Selective COX-2 inhibitor can significantly delay the healing of experimental gastric ulcer in rats, the mechanism of which might be associated with enhanced digestive action of gastric acid on the new granulation tissue at the ulcer base as a result of celecoxib-stimulated gastric acid secretion of the parietal cells.</p>

Protective effect of nitric oxide on gastric mucosa and its relationship to the acid secretion of gastric parietal cells under stress in rats / 中国应用生理学杂志

<p><b>AIM</b>To demonstrate the protective effect of nitric oxide (NO) on gastric mucosa and its relationship to the acid secretion of parietal cells under stress in rats.</p><p><b>METHODS</b>Water immersion-restraint stress (WRS) model in SD rats was performed. The gastric mucosal ulcer index (UI), NO contents in gastric mucosa and H+, K(+) -ATPase activity of parietal cells were measured. The effects of N(G)-nitro-L-arginine methyl ester(L-NAME) and L-arginine (L-Arg) on the H+, K(+)-ATPase activity of parietal cells and stress-induced gastric mucosal lesion were observed.</p><p><b>RESULTS</b>L-NAME pretreatment decreased NO contents in gastric mucosa, activated H+, K(+) -ATPase activity of parietal cells and aggravated gastric mucosal lesion, whereas L-Arg pretreatment increased NO contents, inhibited H+, K(+) -ATPase activity and significantly ameliorated stress-induced gastric mucosal lesion.</p><p><b>CONCLUSION</b>Endogenous nitric oxide plays an important role in protecting gastric mucosa from stress-induced lesion by inhibiting H+, K(+) -ATPase activity of parietal cells.</p>

Erythrocytes may contain a ouabain-insensitive K+-ATPase which plays a role in internal K+ balance

Erythrocytes are useful in evaluating K+ transport pathways involved in internal K+ balance. Several forms of H+,K+-ATPase have been described in nephron segments active in K+ transport. Furthermore, the activity of a ouabain-insensitive isoform of H+,K+-ATPase expressed in collecting duct cells may be modulated by acid-base status. Various assays were performed to determine if a ouabain-insensitive K+-ATPase is present in rat erythrocytes and, if so, whether it plays a role in internal K+ balance. Kinetic studies demonstrated that maximal stimulation of enzyme activity was achieved with 2.5 mM K+ at pH 7.4. Subsequent experiments were performed on erythrocyte membranes collected from animals submitted to varying degrees of K+ homeostasis: control rats, K+-depleted rats, K+-loaded rats, and rats rendered hyperkalemic due to acute renal failure. As observed in the collecting duct cell studies, there was a significant decrease in the activity of ouabain-insensitive K+-ATPase in the erythrocytes of both K+-loaded and metabolically alkalotic K+-depleted rats. However, this enzyme activity in erythrocyte membranes of rats with metabolic acidosis-related hyperkalemia was similar to that of control animals. This finding may be interpreted as resulting from two potentially modulating factors: the stimulating effect that metabolic acidosis has on K+-ATPase and the counteracting effect that hyperkalemia and uremia have on metabolic acidosis. In summary, we present evidence of a ouabain-insensitive K+-ATPase in erythrocytes, whose activity is modulated by acid-base status and K+ levels.

The Comparative Study on the Efficacy of Ranitidine and Rabeprazole in Reflux Laryngitis / 대한이비인후과학회지

BACKGROUND AND OBJECTIVES: Reflux laryngitis gives rise to inflammatory change in the pharyngolaryngeal tissue with various otolaryngologic and respiratory symptoms. Histamine H2 receptor antagonists and H(+)-K(+)-Exchanging ATPase are currently used as therapeutic medications. However, the efficacy of those two drugs on reflux laryngitis has never been proven yet. Therefore, we intended to analyze and compare the efficacy of the two drugs on reflux laryngitis. MATERIALS AND METHOD: Among the patients who had visited the Department of Otolaryngology, those with the total score of greater than 6 and having more than 2 symptoms that score greater than 2, had undergone laryngoscopy. Of these, the patients who had shown greater than 7 on the Belafsky's Reflux Finding Score (RFS) were studied. The RAN (Ranitidine) group (59 subjects) with Ranitidine administered and RAB (Rabeprazole)group (66 subjects) with Rabeprazole were followed up for 12 weeks, and then the efficacy of each drug was evaluated at 2nd, 4th, and 12th week. Then, the Symptom Score Improvement (SSI) and RFS were compared and analyzed. RESULTS: In comparison the RAN group that had Histamine H2 receptor antagonists and prokinetic agents administered to the RAB group that had H(+)-K(+)-Exchanging ATPase and prokinetic agents administered for the improvement of symptoms caused by reflux laryngitis, no difference was observed till after the first 2 weeks. On the evaluation at 4th and 12th week, statistically higher therapeutic efficacy was shown to a great extent in the RAB group. The findings of laryngoscopy at the 12th week also showed higher therapeutic efficacy in the RAB group. In comparison of symptoms between the groups, there were significant differences in pharyngolaryngeal foreign body sense and chronic throat clearing, and laryngeal edema and injection as well. CONCLUSION: For therapy of reflux laryngitis patients with moderately severe symtpoms, the use of H(+)-K(+)-Exchanging ATPase and prokinetic agents were superior in improving symptoms and clinicopathologic findings of larynx than Histamine H2 receptor antagonists and prokinetic agents.

Pantoprazol, o terceiro agente inibidor ATPase K+/H+ / Pantoprazole, the third antiulcer agent K+/H+ ATPase

Trabalho de revisäo sobre pantoprazol quanto à açäo farmacológica, farmacocinética, metabolismo, mecanismomo de açäo, uso terapêutico, dose e administraçäo, comparaçäo com outros fármacos, associaçöes, efeitos adversos e interaçöes medicamentosas.(au)

Cell Biology of H+ Transport in Epithelia

Cell homeostasis of H+ ions has been an object of wide interest in the last two decades, which has led to extended knowledge about a considerable number of membrane transport mechanisms responsible for keeping cell pH within physiological limits. Among these mechanisms the most important are Na+/H+ exchange, the vacuolar H+-ATPase, the H+-K+-ATPase, Cl-/HCO3 - exchange and Na+/HCO3 - cotransport. The present review covers both cellular function and molecular aspects of these transporters, starting from a discussion of the methods used for the determination of cell pH and epithelial H+ transport, and analysing their molecular constitution, cloning and known isoforms, as well as their functional role in the maintenance of cell pH and epithelial transport.

Estudio multicéntrico con pantoprazol en el tratamiento de la enfermedad ácido péptica e México / Multicentric study using pantoprazole in the treatment of peptic acid disease in Mexico

Se realizó un estudio prospectivo multicéntrico en diversas ciudades de la República Mexicana utilizando pantoprazol para el tratamiento de la enfermedad ácido-péptica. Se incluyeron 1,696 pacientes con diagnóstico de enfermedad ácido-péptica. Se recabaron datos personales y relacionados con la enfermedad, método de diagnóstico, tratamiento y resultado al final del mismo. Se encontró que la media de edad en los pacientes del sexo masculino fue 43.9 años y en las mujeres 42.4 años (p = 0.041). El porcentaje de hombres y mujeres fue de 49.6 respectivamente. Existe correlación entre el consumo de alcohol, el diagnóstico de úlcera péptica (p = 0.032) y el dolor epigástrico en ayunas (p = 0.004). De los diagnósticos establecidos, la gastritis tuvo la mayor proporción (21.19 por ciento). Al final del tratamiento, 68 por ciento (1.157 casos) reportaron ausencia total de los síntomas que los motivaron a buscar atención médica. El 96.26 por ciento de los tratamientos se ajustaron a la dosis diaria recomendada de 40 mg. La evaluación global sobre el tratamiento con pantoprazol en relación con los casos tratados fue que 96 por ciento de los investigadores lo consideraron excelente o bueno. Los resultados obtenidos demuestran la efectividad del pantoprazol en el tratamiento de la enfermedad ácido-péptica, con la dosis recomedada de 40 mg al día. En sólo dos casos se suspendió el tratamiento por probables reacciones adversas al medicamento

Na, K-ATPase: a molecular target for Leptospira interrogans endotoxin

On the basis of our report that a glycolipoprotein fraction (GLP) extracted from Leptospira interrogans contains a potent inhibitor of renal Na,K-ATPase, we proposed that GLP-induced inhibition of Na,K-ATPase might be the primary cellular defect in the physiopathology of leptospirosis. The present study was designed to test this hypothesis by determining whether or not 1) GLP inhibits all the isoforms of Na,K-ATPase which are expressed in the tissues affected by leptospirosis, 2) Na,K-ATPase from leptospirosis-resistant species, such as the rat, is sensitive to GLP, 3) GLP inhibits Na,K-ATPase from intact cells, and 4) GLP inhibits ouabain-sensitive H,K-ATPase. The results indicate that in the rabbit, a leptospirosis-sensitive species, GLP inhibits with similar efficiency (apparent IC5O: 120-220 mug protein GLP/ml) all isoforms of Na,K-ATPase known to be expressed in target tissues for the disease. Na,K-ATPase from rat kidney displays a sensitivity to GLP similar to that of the rabbit kidney enzyme (apparent IC50: 25-80 and 50-150 mug protein GLP/ml for rat and rabbit, respectively), indicating that resistance to the disease does not result from the resistance of Na,K-ATPase to GLP. GLP also reduces ouabain-sensitive rubidium uptake in rat thick ascending limbs (pmol mm-1 min-1 ñ SEM; control: 23.8 ñ 1.8; GLP, 88 mug protein/ml: 8.2 ñ 0.9), demonstrating that it is active in intact cells. Finally, GLP had no demonstrable effect on renal H,K-ATPase activity, even on the ouabain-sensitive form, indicating that the active principle of GLP is more specific for Na,K-ATPase than ouabain itself. Although the hypothesis remains to be demonstrated in vivo, the present findings are compatible with the putative role of GLP-induced inhibition of Na,K-ATPase as an initial mechanism in the physiopathology of leptospirosis.

Structure-activity relationship studies of 4-substituted-2-guanidinothiazoles: reversible inhibitors of gastric (H+/K+)-ATPase.

The role of physicochemical factors, electronic and hydrophobic, and a hydrogen donor index in the inhibition of gastric (H+/K+)-ATPase by 4-phenyl-2-guanidinothiazoles and the 4-indolyl-2-guanidinothiazoles has been quantitatively analysed. For the first congeneric series, the resonance effect of the ortho- and para-substituents and hydrogen donor property of the meta-substituent in the phenyl ring play crucial role, whereas for 4-indolyl analogues, the hydrophobicity and electron withdrawing effect of X-substituents in the indolyl ring are shown to be important decisive factors. Also the substitution of the guanidine moiety, e.g. by benzyl, raises the activity of proton pump inhibitors. The substitution at 5-position of thiazole ring does not enhance the potency.