Immunostimulatory effect of natural clinoptilolite as a possible mechanism of its antimetastatic ability.
OBJECTIVE
Many biochemical processes are closely related to ion exchange, adsorption, and catalysis. Zeolites reversibly bind small molecules such as oxygen or nitric oxide; they possess size and shape selectivity, the possibility of metalloenzyme mimicry, and immunomodulatory activity. These properties make them interesting for pharmaceutical industry and medicine.


METHODS
The experiments were performed on mice. Different biochemical and molecular methods were used.


RESULTS
Micronized zeolite (MZ) administered by gastric intubation to mice injected with melanoma cells significantly reduced the number of melanoma metastases. In mice fed MZ for 28 days, concentration of lipid-bound sialic acid (LSA) in serum increased, but lipid peroxidation in liver decreased. The lymphocytes from lymph nodes of these mice provoked a significantly higher alogeneic graft-versus-host (GVH) reaction than cells of control mice. After i.p. application of MZ, the number of peritoneal macrophages, as well as their production of superoxide anion, increased. However, NO generation was totally abolished. At the same time, translocation of p65 (NFkappaB subunit) to the nucleus of splenic cells was observed.


CONCLUSIONS
Here we report antimetastatic and immunostimulatory effect of MZ and we propose a possible mechanism of its action.
Pavelic
K
K
Rudjer Boskovic Institute, Division of Molecular Medicine, Bijenicka 54, HR-10000 Zagreb, Croatia. pavelic@rudjer.irb.hr
Katic
M
M
Sverko
V
V
Marotti
T
T
Bosnjak
B
B
Balog
T
T
Stojkovic
R
R
Radacic
M
M
Colic
M
M
Poljak-Blazi
M
M
D000276:Adjuvants, Immunologic; D000818:Animals; D000970:Antineoplastic Agents / Q000627:therapeutic use*; D002455:Cell Division / Q000187:drug effects; D006087:Graft vs Host Reaction / Q000276:immunology; D008214:Lymphocytes / Q000276:immunology; D017737:Macrophages, Peritoneal / Q000166:cytology* / Q000187:drug effects / Q000502:physiology; D008546:Melanoma, Experimental / Q000473:pathology*; D051379:Mice; D008810:Mice, Inbred C57BL; D008808:Mice, Inbred CBA; D008815:Mice, Inbred Strains; D019158:N-Acetylneuraminic Acid / Q000097:blood; D016328:NF-kappa B / Q000378:metabolism; D009362:Neoplasm Metastasis / Q000517:prevention & control*; D021122:Protein Subunits; D012016:Reference Values; D013154:Spleen / Q000276:immunology; D013481:Superoxides / Q000378:metabolism; D017392:Thiobarbituric Acid Reactive Substances / Q000032:analysis; D017641:Zeolites / Q000627:therapeutic use*
D000276:Adjuvants, Immunologic; D000970:Antineoplastic Agents; D016328:NF-kappa B; D021122:Protein Subunits; D017392:Thiobarbituric Acid Reactive Substances; D013481:Superoxides; C083175:clinoptilolite; D017641:Zeolites; D019158:N-Acetylneuraminic Acid