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KMID : 0350519930460020689
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Journal of Catholic Medical College
1993 Volume.46 No. 2 p.689 ~ p.700
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Protective Effects of Fosfomycin on the Experimental Nephrotoxicity Induced by Cyclosporine A
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Abstract
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Nephrotoxicity directly attributable to cyclosporine A(CsA) administration remains an obstacle to its successful use. Attempts to achieve the significant immunosuppression with CsA and minimal nephrotoxicity have, still, met with minimal success.
It has
been reported that cytoprotective effects of fosfomycin(FOM) exist for CsA induced nephrotoxicity and it´s because FOM protects the lysosomal membrane integrity of rat kidney. However, a detailed study of the protective effects of FOM on the CsA
induced
nephrotoxicity has not been fully established.
This study was designed to evaluate whether a protective effect of FOM exrsted for CsA induced nephrotoxicity functionally and ultrastructurally.
5 male Sprague-Dawley ats were divided into 6 groups: (1) Group I -control group receiving normal saline alone (2) Group II -Fom 200 mg/kg/day treated group (3) Group III-FOM 400 mg/kg/day treated group (4) Group Ⅳ-CsA(30 mg/kg/day) treated
group
(5)
Group V -CsA(30 mg/kg/day) with FOM 200 mg/kg/day treated group (6) GroupⅣ-CsA(30 mg/kg/day) with FOM 400 mg/kg/day. All experimental rats were treated daily through intraperitoneal injection for 3 weeks and whole blood samples were collected at
weekly
intervals over the 3 week-course of the experiment and right kidneys of all animals were obtained. Protective effects of FOM on the nephrotoxicity induced by CsA were evaluated by measuring serum creatinine and by light and electron microscopy
and
serum
CsA levels were dedtermined by radioimmunoassay.
@ES The resuts were as follows :
@EN 1. There were normal increases in body weight in group Ⅰ, ⅡandⅢ . But in group Ⅳ, marked decrease in body weight was observed on 2 weeks and was slightly recovered on 3 weeks. And similar changes were noted in group V and Ⅳ.
2. Slight detease of kidney weight(kidney weight/body weight×10E3) was observed in group Ⅳ(3.82±0.81) compared to groupⅠ(4.42±0.58) and this change was slightly increased in group V(4.68±0.82) and Ⅵ(4.46±0.76). But these changes were not
considered statistically significant.
3. The significant increases(1.48±0.23, 1.63±0.16, 1.66±0.22 mg/ml) of serum creatinine were observed on 1, 2 and 3 weeks in group Ⅳcompared to groupⅠ(0.49±0.10, 0.56±0.06, 0.52±0.11 mg/ml, P<0.001). However, there were no significant
differences among group Ⅳ, Ⅴ and Ⅵ.
The concentrations of serum CsA in groupⅣ(4935.4±762.5, 5849.2±123.1, 4923.7±998.4 ng/ml) measured on 1, 2 and 3 weeks were simiar in group V (4975.9±94.8, 5415.4±794.0, 4655.1±918.7 ng/ml) and group Ⅵ(5134.7±493.7, 5981.9±823.4,
4548.3±912.4
ng/ml).
4. Light microscopic examinations showed many vacuoles of renal proximal tubular cells in group Ⅳ and Ⅴ , but these vacuoles were not observed in groupⅥ . In transmission electron microscopic examination, several vacuoles were observed and
the
number and the size of lysosome were increased in group Ⅳ andⅤ compared to group I. And myeloid body was occasionally observed. However, these changes were not occurred in group Ⅵ.
These experimental results imply that FOM has a cytoprotective effect on CsAinduced nephrotoxicity without alteration of serum CsA concentration but, in low dose of FOM, there is no effect for protection of CsA induced nephrotoxicity.
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KEYWORD
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