Polaprezinc protects gastric mucosal cells from noxious agents through antioxidant properties in vitro.
BACKGROUND: Polaprezinc has been shown to exert an anti-oxidant property in a tube experiment, protect gastric mucosa from experimental ulcerations in vivo, and accelerate the healing of gastric ulcer in humans. AIM: To examine a possible protective effect of polaprezinc on oxidant-mediated injury in primary monolayer cultures of rat gastric fundic mucosa. METHODS: Cytotoxicity was quantified by measuring 51Cr release. Whether or not polaprezinc exerts an antioxidant property was investigated by determining the effect of this agent on hydrogen peroxide (H2O2)-induced injury. The effects of polaprezinc on superoxide (O2-. ) generation as well as on ethanol (EtOH)-induced injury were also examined. Generation of O2-. was assessed by the reduction in cytochrome c. RESULTS: H2O2 caused a time- and dose-dependent increase in 51Cr release. The dose-response curve of 51Cr release by H2O2 shifted to the right in the presence of polaprezinc. Polaprezinc, at submillimolar concentrations, prevented H2O2-induced 51Cr release. EtOH also caused a dose-dependent increase in 51Cr release, which was prevented by the addition of polaprezinc. The incubation of cells with EtOH caused an increase in cytochrome c reduction, as the concentrations of EtOH increased. Polaprezinc inhibited EtOH-induced cytochrome c reduction. Protection by polaprezinc was microscopically associated with the prevention of monolayer disruption. CONCLUSIONS: Polaprezinc is antioxidative and directly protects gastric mucosal cells from noxious agents through its antioxidant properties in vitro. This finding may provide the theoretical basis for the usage of an antiulcer drug with antioxidant properties for the treatment of gastric inflammation, such as that induced by ethanol. (+info)
Polaprezinc, a mucosal protective agent, in combination with lansoprazole, amoxycillin and clarithromycin increases the cure rate of Helicobacter pylori infection.
AIM: To evaluate the efficacy of polaprezinc, a mucosal protective agent, in combination with a 7-day triple therapy containing lansoprazole, amoxycillin and clarithromycin, as a treatment for Helicobacter pylori. METHODS: Sixty-six consecutive patients suffering from dyspeptic symptoms with H. pylori infection were randomly allocated to one of two regimens: one group (LAC; n = 31) received lansoprazole 30 mg b.d., amoxycillin 500 mg b.d. and clarithromycin 400 mg b.d. for 7 days. The other group (LACP; n = 35) received the LAC regimen plus polaprezinc 150 mg b.d. for 7 days. H. pylori status was evaluated by rapid urease test, histology and culture at entry and 4 weeks after treatment. RESULTS: Five patients did not complete the treatment: no follow-up endoscopy was performed on two patients in the LAC group; one patient in the LAC group and two in the LACP group had their treatment stopped due to severe diarrhoea. By per protocol analysis, H. pylori eradication was achieved in 24 of the 28 evaluable patients (86%; 95% CI: 72-100%) after LAC therapy, and in 33 of the 33 evaluable patients (100%) after LACP therapy (P < 0.05). On intention-to-treat analysis, the rates of eradication were 24 of 31 patients (77%; 95% CI: 62-93%) in the LAC group, and 33 of 35 patients (94%; 95% CI: 86-100%) in the LACP group (P < 0.05). CONCLUSION: A 7-day triple therapy with lansoprazole, amoxycillin and clarithromycin is effective in H. pylori eradication, but this regimen is significantly improved by the addition of polaprezinc. (+info)
Carnosine stimulates vimentin expression in cultured rat fibroblasts.
Two-dimensional electrophoretic gel profiles were compared between rat 3Y1 fibroblasts cultured in the presence and absence of 30 mM L-carnosine (beta-alanyl-L-histidine) for one week without any replenishment of medium. While a number of cellular proteins changed their expression levels by the addition of carnosine, we identified one of the most prominently varied proteins as vimentin. Immunoblot analysis with anti-vimentin antibody demonstrated that the vimentin levels increased about 2-fold after one-week culture in the presence of carnosine. We also confirmed that the increase of vimentin expression was dependent on the concentration of carnosine added to the medium. Moreover, when cultured cells were stained with anti-vimentin antibody and observed by light microscopy, most cells grown in the presence of carnosine were found to have markedly developed vimentin filaments. The increase of vimentin expression was also observed by adding with carnosine related dipeptides, N-acetylcarnosine and anserine. (+info)
Polaprezinc down-regulates proinflammatory cytokine-induced nuclear factor-kappaB activiation and interleukin-8 expression in gastric epithelial cells.
Gastric epithelial chemokine response is a primary factor in the induction of gastric inflammation associated with Helicobacter pylori infection. Because sustained inflammation is a risk for gastric mucosal damage, agents that down-regulate inflammatory responses may be of therapeutic significance. We examined the effect of polaprezinc, a potent antiulcer agent, on proinflammatory cytokine-induced interleukin (IL)-8 expression in gastric epithelial cells. Because IL-8 expression is regulated by the transcription factor nuclear factor-kappaB (NF-kappaB), we also examined the effect of polaprezinc on NF-kappaB activity. MKN28 cells were used as a model of gastric epithelial cells. Secreted IL-8 was quantified by IL-8 specific enzyme-linked immunosorbent assay, and IL-8 mRNA expression was examined by Northern blot analysis. NF-kappaB activity was analyzed by electrophoretic mobility shift assay. Western blot analysis with anti-phospho-IkappaB-alpha antibody was performed to assess IkappaB-alpha phosphorylation. Polaprezinc-suppressed IL-8 secretion induced by tumor necrosis factor alpha (TNF-alpha) or IL-1beta in a dose-dependent manner. IL-8 mRNA expression also was inhibited by polaprezinc. NF-kappaB activation in response to TNF-alpha, IL-1beta, phorbol ester, and H(2)O(2) was down-regulated by polaprezinc. Western blot analysis showed inhibition of TNF-alpha-induced IkappaB-alpha phosphorylation in the presence of polaprezinc. Collectively, these results suggest that polaprezinc is a novel type of anti-inflammatory agent that down-regulates inflammatory responses of gastric mucosal cells. (+info)
Hydrogen peroxide-mediated Cu,Zn-superoxide dismutase fragmentation: protection by carnosine, homocarnosine and anserine.
The fragmentation of human Cu,Zn-superoxide dismutase (SOD) was observed during incubation with H(2)O(2). Hydroxyl radical scavengers such as sodium azide, formate and mannitol protected the fragmentation of Cu,Zn-SOD. These results suggested that *OH was implicated in the hydrogen peroxide-mediated Cu,Zn-SOD fragmentation. Carnosine, homocarnosine and anserine have been proposed to act as anti-oxidants in vivo. We investigated whether three compounds could protect the fragmentation of Cu,Zn-SOD induced by H(2)O(2). The results showed that carnosine, homocarnosine and anserine significantly protected the fragmentation of Cu,Zn-SOD. All three compounds also protected the loss of enzyme activity induced by H(2)O(2). Carnosine, homocarnosine and anserine effectively inhibited the formation of *OH by the Cu,Zn-SOD/H(2)O(2) system. These results suggest that carnosine and related compounds can protect the hydrogen peroxide-mediated Cu,Zn-SOD fragmentation through the scavenging of *OH. (+info)
Heme-dependent radical generation: possible involvement in antimalarial action of non-peroxide microbial metabolites, nanaomycin A and radicicol.
Antimalarial screening was performed for microbial metabolites that simulate artemisinin in their mode of action, a potent antimalarial component of an herbal remedy with a characteristic peroxide structure. Nanaomycin A was identified in this screen as an antimalarial compound, together with radicicol and several other compounds already reported (J. Antibiotics 51: 153 approximately 160, 1998). Nanaomycin A inhibited in vitro growth of the human malaria parasite Plasmodium falciparum with an IC80 value of 33.1 nM. It was as potent as radicicol and about 1/10 as potent as artemisinin. Studies on the mode of action suggested that the antimalarial action of the two non-peroxides, nanaomycin A and radicicol, involved heme-dependent radical generation, as is for the peroxide artemisinin. Namely, the inhibition of in vitro growth of malaria parasite by nanaomycin A or radicicol was reversed by tocopherol, a radical scavenger added to the assay mixture. Secondly, in a reaction system established for radical detection, in which a test radical donor and beta-alanylhistidine as a radical recipient were incubated with and without hemin, the two compounds caused heme-dependent decreases of beta-alanylhistidine, as did artemisinin. Among the 14 microbial metabolites identified during this screening, a correlation was observed between antimalarial activity and heme-dependent radical generating activity. (+info)
Amino acid flux in ruminal and gastric veins of sheep: effects of ruminal and omasal injections of free amino acids and carnosine.
The possibility of free amino acid (FAA) and peptide absorption across the ruminant stomach wall was studied in multicatheterized wethers fed every 12 h. During the last third of the feeding cycle, two intraruminal or intraomasal injections of solutions containing increasing amounts of Ser, Gly, Val, Met, Phe, Lys, and carnosine were successively performed. Before injections, a net uptake of each of these FAA was measured in the ruminal and the gastric veins. The ruminal injections produced a linear increase in ruminal FAA concentration. The highest ruminal concentrations (observed with 3 g of FAA and carnosine) ranged between 5 and 14 mM. After ruminal injections, Ser (P < .05), Gly (P < .05), Val (P < .05), Met (P < .10), and Lys (P < .10) uptake decreased and carnosine net release linearly increased (P < .05), suggesting absorption across the ruminal epithelium. Owing to the low net flux generated by high ruminal concentration, the ruminal epithelium permeability to these molecules seemed to be low. After omasal injections, net flux of injected FAA were not modified, suggesting a low permeability of the gastric epithelia to FAA. Carnosine net release linearily increased (P < .05) with increasing level of carnosine injection, indicating the possibility of dipeptide absorption at the gastric level. This study demonstrated in vivo that the stomach epithelia possess the capacity to absorb FAA and small peptides; however, the permeability of these epithelia to these molecules seemed limited. (+info)
Effects of carnosine and related compounds on the stability and morphology of erythrocytes from alcoholics.
The effects of carnosine and related compounds on erythrocytes from alcoholics were studied. In their presence, erythrocytes showed an increased ability to resist haemolysis and showed a more normal morphology, with carnosine and N-acetyl-carnosine being the most effective compounds. These beneficial properties of the dipeptides do not appear to be directly related to their antioxidant or buffering properties. (+info)