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KMID : 0350519920450020623
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Journal of Catholic Medical College
1992 Volume.45 No. 2 p.623 ~ p.633
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Effect of Aminoglycoside Antibiotics on Cellular ATP Content in Isolated Rat Nephron Segments
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Abstract
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A lot of things have been known about toxic effects o faminoglycoside antibiotics on the kidney and the inner ear. Aminoglycoside-induced tubular cell damage results in nonoliguric acute renal failure(ARF). The mechanism of aminoglycoside-induced
nephrotoxicity has been extensively studied in animals but remains speculative. Accumulation of aminoglycosides in the renal cortex precedes the histopathologic changes , such as necrosis and regeneration of the proximal tubule and hyaline cast
formation in the loop of Henle.
Recently, the predominance o finjury to the medullary tubules has neen reported in human ARF. Therefore, it is needed to clarify the dominary site of injury by aminoglcoside in different nephron segments.
Aminoglycoside-induced nephrotoxicity in experimental animals can be alleviated by dietary calciam and KCI lcading, inducing diabetes mellitus, and giving nitrendipine while prior volume contraction and concomitant treatment of diltiazem further
aggravate aminoglycoside-induced nephrotoxicity. Among these factors to modify the severity of aminoglycoside-induced nephrotoxicity, calcium may play a preventive role in aminoglycoside-induced acute renal failure.
This study was undertaken to investigate intrarenal toxic action of aminoglycoside by measuring cellular adenosine triphosphate (ATP) content and to define the role of calcium in aminoglycosideinduced nephrotoxicity in vitro.
Seventy five male Sprague-Dawley weighing 200 to 250 g were used in this experiment. The nephron segments were dissected from renal slices under the stereomicroscopic observation after treatment of 0.1% collagenase. Cellular ATP content was
measured by
microchemiluminescence method.
@ES The results were as follows:
@EN 1. In Si, the first, part of proximal tubule, cellular ATP content was significantly decreased by 1mM gentamicin. But not in streptomycin and kanamycin at the same concentration.
2. Gentamicin decreased cellular ATP content in a dose-dependent manner. The administration of 0.1mM gentamicin induced the decrement of cellular ATP content in S1. The maximum effect of gentamicin on cellular ATP content was obtained at 5 mM in
S1.
3. A 15-min incubation increased the ATP content of S1 in the absence of the substrate. After then, cellular ATP content in S1 was decreased gradually with time course.
4. In al nephron segments except S1, 15-min incubation reduced the ATP content. Especially, the decrement of ATP content in S2 was the most prominent. Glomerulrs and S3 showed singificnat decrement of ATP content. In distal nephrons. 15-min
incubation
could not induce the decrement of cellular ATP content. These results indicate that nephron segments differ from one another in cellular ATP content according to duration of incubation. Gentamicin administration produced a marked decrement of
cellular
ATP content in S1, S3 and medullary thick ascending limb(MTAL). But there were no significant differences of cellular ATP content in other segments between control and gentamicin groups.
5. In S1, significant decrement of cellular ATP content was found in the treatment of 0.1mM and 1mM verapamil. But 0.01 mM verapamil and high calcium(10 mM) couldn't change cellular ATP content.
6. 0.01 mM verapamil enhanced the effect of gentamicin on the cellular ATP content in S1.
With the above results, it is concluded that aminoglycoside-induced nephrotoxicity is associated with the cellular injury of proximal tubule and MTAL, and verapamil enhances gentamicin nephrotoxicity.
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