Publication: Inhibition of gentamicin-induced nephrotoxicity by lithium in rat
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Date
1993
Authors
Samadian, T. ; Dehpour, A.R. ; Amini, Sh. ; Nouhnejad, P.
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Publisher
Murcia : F. Hernández
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DOI
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info:eu-repo/semantics/article
Description
Abstract
Daily intraperitoneal injection of gentamicin
in doses of 2,4 and 10 mglkglday for 5 consecutive days
produced proximal tubular necrosis in male albino rats
as assessed by ultrastructural findings from electron
microscopic observations. With respect to nephrotoxicity,
aminoglycoside antibiotics (AGs) have been
shown to concentrate in the lysosomes of kidney
proximal tubular cells to inhibit the activities of
phospholipases A and C, including a phospholipidosis,
characterized by the formation of myeloid bodies. It has
been suggested that the nephrotoxicity of AGs is related
to the extent of this phospholipidosis. The concurrent
therapy of lithium in doses of 5 and 10 mEqIkglday,
administered subcutaneously, 24 hours prior to
gentamicin administration for the same period, proved
effective in reducing the gentamicin-induced
phospholipidosis in kidney as judged by reduction in
lysosomal myeloid bodies to an amount of 26-45
percent. It is well known that lithium interferes with
phosphatidylinositol turnover and reduces the cellular
availability of myoinositol which is needed for the
resynthesis of membrane poliphosphoinositides. Thus,
the inhibitory effect of lithium on gentamicin-induced
nephrotoxicity may be due to interference of lithium
with phosphoinositide cycle.
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