MEDLINE: Biomedicine, 1990-  @  Wed Sep 17 12:43:08 1997

Document 114
Accession No.: 97261625.
Author:        Zalups-R-K.  Lash-L-H.
Title:         Depletion of glutathione in the kidney and the renal
disposition of administered inorganic mercury.
Source:        Drug-Metab-Dispos.  1997 Apr.  25(4).  P 516-23.
Journal Title: DRUG METABOLISM AND DISPOSITION.

Abstract:      

The primary aim of the present study was to evaluate the
effects of different means of depleting glutathione (GSH) in
the kidneys and liver on the renal and hepatic accumulation and
disposition of a nontoxic dose of inorganic mercury.
Renal and hepatic disposition of mercury were evaluated
1 hr after the intravenous administration of a 0.5 mumol/kg
dose of mercuric chloride in control rats and rats pretreated
with acivicin, buthionine sulfoximine (BSO), or diethylmaleate
(DEM). Pretreatment with acivicin or DEM caused significant
decreases in the net renal accumulation of mercury
during the first hour after the injection of mercuric chloride.
The primary effects of these two pretreatments occurred in the
renal cortex, although pretreatment with DEM also caused
significant decreases in the concentration of mercury in
the outer stripe of the outer medulla. Despite the fact that
pretreatment with BSO caused a reduction in the renal content
of GSH, comparable with that caused by DEM, pretreatment with
BSO had no significant effect on the renal disposition of
mercury. Pretreatment with acivicin, BSO, or DEM also
caused significant decrease in measurable reduced GSH, with BSO
and DEM having the most pronounced effects. Injection of the
nontoxic dose of mercuric chloride after pretreatment with
acivicin resulted in slightly, but significantly, decreased
hepatic content of mercury. Interestingly, pretreatment
with BSO or DEM actually caused significant increases in the
hepatic content of mercury 1 hr after the injection of
mercuric chloride. We postulate that this effect was due to a
diminished ability of hepatocytes to export mercuric conjugates
of GSH out into either the bile or blood. The results of this
study indicate that depletion of renal GSH by conjugation
reactions between GSH and DEM leads to an acute reduction in
the renal accumulation of inorganic mercury. However,
the results also indicate that depletion of renal levels of GSH
by inhibition of GSH synthesis does not affect acutely the
ability of the kidneys to accumulate inorganic mercury.
Thus, it seems that factors in addition to intracellular GSH
status play an important role in the renal
accumulation/retention of inorganic mercury.
Holdings:      Chemistry Periodicals
  CALL NUMBER: W1 DR536
  LIB HAS: v.1-22 (1973-1994)
Health Sciences Serials
  SHELVED BY TITLE: Drug metabolism and disposition
  CALL NUMBER: W1 DR536
  LIB HAS: v.1(1973)-v.19(1991)
    v.20:n.1,3-6(1992:Jan/Feb,May/Jun-Nov/Dec) v.21(1993)--