zinc L-carnosine and ulcers!!!

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Jpn J Pharmacol. <javascript:AL_get(this, 'jour', 'Jpn J

Pharmacol.');> 1995 Apr;67(4):271-8. Related Articles,

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67.271?from=PubMed>

*Residence time of polaprezinc (zinc L-carnosine complex) in the rat

stomach and adhesiveness to ulcerous sites.*

*Furuta S*

<http://www.ncbi.nlm.nih.gov/entrez/query.fcgi?db=pubmed & cmd=Search & itool=pubmed\

_Abstract & term=%22Furuta+S%22%5BAuthor%5D>,

*Toyama S*

<http://www.ncbi.nlm.nih.gov/entrez/query.fcgi?db=pubmed & cmd=Search & itool=pubmed\

_Abstract & term=%22Toyama+S%22%5BAuthor%5D>,

*Miwa M*

<http://www.ncbi.nlm.nih.gov/entrez/query.fcgi?db=pubmed & cmd=Search & itool=pubmed\

_Abstract & term=%22Miwa+M%22%5BAuthor%5D>,

*Itabashi T*

<http://www.ncbi.nlm.nih.gov/entrez/query.fcgi?db=pubmed & cmd=Search & itool=pubmed\

_Abstract & term=%22Itabashi+T%22%5BAuthor%5D>,

*Sano H*

<http://www.ncbi.nlm.nih.gov/entrez/query.fcgi?db=pubmed & cmd=Search & itool=pubmed\

_Abstract & term=%22Sano+H%22%5BAuthor%5D>,

*Yoneta T*

<http://www.ncbi.nlm.nih.gov/entrez/query.fcgi?db=pubmed & cmd=Search & itool=pubmed\

_Abstract & term=%22Yoneta+T%22%5BAuthor%5D>.

Central Research Laboratories, Zeria Pharmaceutical Co., Ltd., Saitama,

Japan.

Polaprezinc, an insoluble zinc complex of L-carnosine, exhibits

anti-ulcer effects by acting directly on mucosal lesions. The

disposition of polaprezinc in the stomach was studied to clarify the

usefulness of its structure as an insoluble complex. The time courses of

14C-radioactivity in the gastric contents and gastric tissues were

parallel to those of 65Zn after oral administration of a mixture of

14C-polaprezinc and 65Zn-polaprezinc (14C-, 65Zn-polaprezinc) to rats.

The gastric contents of 14C-polaprezinc and 65Zn-polaprezinc were

greater than those of 14C-L-carnosine and 65ZnSO4. Mean residence times

(MRT) of 14C-polaprezinc and 65Zn-polaprezinc in the stomach were almost

the same (ca. 2 hr), and they were double those of 14C-L-carnosine and

65ZnSO4. In gastric tissues, the area under the concentration curves

(AUC0-8 hr) of 14C-polaprezinc and 65Zn-polaprezinc were 1.7 times

greater than those of 14C-L-carnosine and 65ZnSO4, respectively. After

administration of 14C-, 65Zn-polaprezinc to rats with acetic

acid-induced ulcers, 14C and 65Zn-radioactivities in the ulcerous sites

were very similar and greater than those of 14C-, 65Zn-polaprezinc

dissolved in acid. In conclusion, polaprezinc is retained in the stomach

longer and adheres to the ulcerous sites more than zinc or L-carnosine.

The characteristics of this compound may arise from its insolubility and

contribute to its strong pharmacological action.

Vol. 291, Issue 1, 345-352, October 1999

*Polaprezinc Down-Regulates Proinflammatory Cytokine-Induced Nuclear

Factor-kappa B Activiation and Interleukin-8 Expression in Gastric

Epithelial Cells^1 *

* Tadahito Shimada, Naomi Watanabe, Yukio Ohtsuka, Motoya Endoh, Kazuo

Kojima, Hideyuki Hiraishi and Akira Terano *

Second Department of Internal Medicine, Dokkyo University School of

Medicine, Mibu, Tochigi, Japan

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-kappa B

(NF-kappa , we also examined the effect^ of polaprezinc on NF-kappa B

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-kappa B activity was analyzed^ by electrophoretic

mobility shift assay. Western blot analysis^ with anti-phospho-Ikappa

B-alpha antibody was performed to assess Ikappa B-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-kappa B 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 Ikappa B-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.

Aliment Pharmacol Ther. <javascript:AL_get(this, 'jour', 'Aliment

Pharmacol Ther.');> 1999 Feb;13(2):261-9. Related Articles,

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le & sid=nlm:pubmed & issn=0269-2813 & date=1999 & volume=13 & issue=2 & spage=261>

*Polaprezinc protects gastric mucosal cells from noxious agents

through antioxidant properties in vitro.*

*Hiraishi H*

<http://www.ncbi.nlm.nih.gov/entrez/query.fcgi?db=pubmed & cmd=Search & itool=pubmed\

_Abstract & term=%22Hiraishi+H%22%5BAuthor%5D>,

*Sasai T*

<http://www.ncbi.nlm.nih.gov/entrez/query.fcgi?db=pubmed & cmd=Search & itool=pubmed\

_Abstract & term=%22Sasai+T%22%5BAuthor%5D>,

*Oinuma T*

<http://www.ncbi.nlm.nih.gov/entrez/query.fcgi?db=pubmed & cmd=Search & itool=pubmed\

_Abstract & term=%22Oinuma+T%22%5BAuthor%5D>,

*Shimada T*

<http://www.ncbi.nlm.nih.gov/entrez/query.fcgi?db=pubmed & cmd=Search & itool=pubmed\

_Abstract & term=%22Shimada+T%22%5BAuthor%5D>,

*Sugaya H*

<http://www.ncbi.nlm.nih.gov/entrez/query.fcgi?db=pubmed & cmd=Search & itool=pubmed\

_Abstract & term=%22Sugaya+H%22%5BAuthor%5D>,

*Terano A*

<http://www.ncbi.nlm.nih.gov/entrez/query.fcgi?db=pubmed & cmd=Search & itool=pubmed\

_Abstract & term=%22Terano+A%22%5BAuthor%5D>.

Second Department of Internal Medicine, Dokkyo University School of

Medicine, Mibu, Tochigi, Japan.

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.