Elevated blood iron level in susceptible patients with underlying hepatic diseases is thought to play an important role in the pathogenesis of V. vulnificus septicemia. This study was performed in order to develop an effective therapeutic regimen
involving antibiotic and hypoferremic treatment, Firstly, effects of iron and iron-specific chelator deferoxamine(Df) adminstration on the virulence of V. vulnificus in murine system were observed. To our disappointment, deferoxamine potentiated
the
virulence of V. vulnificus greatly rather than showing any therapeutic effect.
Consequently, calcium disodium EDTA(CaEDTA), which has chelating activity over wide range of divalent cations was recommended as one of the effective therapeutic agents in treating various heavy metal poisonings. was selected as an alternative
hypoferremic agent. And the feasability of calcium disodium EDTA(CaEDTA) as an adjuvant therapeutic agent to doxycycline(DX)in treating V. vulnificus septicemia was evaluated in vivo using ICR mice whose livers were artificially damaged by CCl4.
In
order to understand the mode of action of CaEDTA, in vitro combined effect of CaEDTA and DX was evaluated also. Admindtration of ferric ammonium citrate(FAC) and Df resulted in the decrease in LD50 by about 225 and 460 fold, respectively. When
FAC
and
Df were adminstered in combination, LD50 synergistically decreased by about 4,800 fold, which is 22 or 11 times less than those of the test groups administered singly with FAC or Df. LD50 in CCl4 treated group decreased by about 380 fold. In CCl4
non-treated mice DX treatment resulted in the increase of LD50 by about 560 fold in comparison with that of control while CaEDTA treatment showed no significant change. In CCl4 treated mice, treatment with DX or CaEDTA resulted in the increase of
LD50
by about 100 and 3 fold respectively. On the other hand, treatment with both DX and CaEDTA resulted in about 410 fold increase, which indicates that the two agents synergistically protect the host in combination, When the two agents were combined
in
vitro, synergictic antimicrobial activity was observed by using MS-2(Abbott Co., USA), which implies that the in vivo synergism might originate from synergistic antibacterial activity of the two agents against. V. vulnificus. Above reults imply
that
resolute adminstration of adjuvant hypoferremic agent in conjuction with antibiotic treatment may improve that therapeutic outcome.
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