OK-432 treatment increases matrix metalloproteinase-9 production and improves dimethylnitrosamine-induced liver cirrhosis in rats.

  • Authors:
    • T Ueno
    • K Sujaku
    • S Tamaki
    • R Ogata
    • M Kin
    • T Nakamura
    • M Sakamoto
    • T Torimura
    • K Mitsuyama
    • S Sakisaka
    • M Sata
    • K Tanikawa
  • View Affiliations

  • Published online on: May 1, 1999     https://doi.org/10.3892/ijmm.3.5.497
  • Pages: 497-1000
Metrics: Total Views: 0 (Spandidos Publications: | PMC Statistics: )
Total PDF Downloads: 0 (Spandidos Publications: | PMC Statistics: )


Abstract

Kupffer cells are major matrix metalloproteinase-producing cells in the liver. The production of metalloproteinases in Kupffer cells may contribute to the improvement of liver fibrosis inducing liver cirrhosis. In this study, we examined the effect of the OK-432 (a biological response modifier) on the dimethylnitrosamine-induced liver cirrhosis in rats. Dimethylnitrosamine (10 microg/ml) was injected intraperitoneally into 20 male Wistar rats 3x/week for 4 weeks. For the subsequent 4 weeks, the animals were injected with saline (1 ml, 1x/week) (Group I, n=10) or OK-432 (1 Klinishe Einheit, 1x/week) (Group II, n=10). The control rats were injected with 1 ml saline for the initial 4 weeks and subsequent 4 weeks (Group III, n=10). The degree of hepatic fibrosis, the immunolocalization of type IV collagen, hyaluronic acid, and alpha-smooth muscle actin, and the mRNA expression by Northern blotting and the activity by gelatin zymography of metalloproteinase-9 were evaluated. Serum aminotransferase, hyaluronic acid, interleukin-1beta and tumor necrosis factor-alpha levels were measured. The deposition of á-smooth muscle actin and extracellular matrix containing type IV collagen and hyaluronic acid was markedly suppressed by OK-432. The mRNA expression and the activity of metalloproteinase-9 were markedly increased by OK-432. The serum aminotransferase and hyaluronic acid levels were decreased by OK-432. The serum interleukin-1 and tumor necrosis factor-alpha values were lower than the detectable limit in all samples from all three groups. These results indicate that OK-432 increased the production of metalloproteinase-9 and improved the rat dimethylnitrosamine-induced liver cirrhosis. OK-432 is suggested to be useful for the treatment of liver cirrhosis.

Related Articles

Journal Cover

May 1999
Volume 3 Issue 5

Print ISSN: 1107-3756
Online ISSN:1791-244X

Sign up for eToc alerts

Recommend to Library

Copy and paste a formatted citation
x
Spandidos Publications style
Ueno T, Sujaku K, Tamaki S, Ogata R, Kin M, Nakamura T, Sakamoto M, Torimura T, Mitsuyama K, Sakisaka S, Sakisaka S, et al: OK-432 treatment increases matrix metalloproteinase-9 production and improves dimethylnitrosamine-induced liver cirrhosis in rats.. Int J Mol Med 3: 497-1000, 1999
APA
Ueno, T., Sujaku, K., Tamaki, S., Ogata, R., Kin, M., Nakamura, T. ... Tanikawa, K. (1999). OK-432 treatment increases matrix metalloproteinase-9 production and improves dimethylnitrosamine-induced liver cirrhosis in rats.. International Journal of Molecular Medicine, 3, 497-1000. https://doi.org/10.3892/ijmm.3.5.497
MLA
Ueno, T., Sujaku, K., Tamaki, S., Ogata, R., Kin, M., Nakamura, T., Sakamoto, M., Torimura, T., Mitsuyama, K., Sakisaka, S., Sata, M., Tanikawa, K."OK-432 treatment increases matrix metalloproteinase-9 production and improves dimethylnitrosamine-induced liver cirrhosis in rats.". International Journal of Molecular Medicine 3.5 (1999): 497-1000.
Chicago
Ueno, T., Sujaku, K., Tamaki, S., Ogata, R., Kin, M., Nakamura, T., Sakamoto, M., Torimura, T., Mitsuyama, K., Sakisaka, S., Sata, M., Tanikawa, K."OK-432 treatment increases matrix metalloproteinase-9 production and improves dimethylnitrosamine-induced liver cirrhosis in rats.". International Journal of Molecular Medicine 3, no. 5 (1999): 497-1000. https://doi.org/10.3892/ijmm.3.5.497