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KMID : 0350519940470020971
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Journal of Catholic Medical College
1994 Volume.47 No. 2 p.971 ~ p.984
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Changes of Male Reproductive Organs Induced by Cyclosporine-A and the Protective Effect of Fosfomycin in Rat
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Abstract
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Cyclosporine-A(CsA) has been used extensively for immunosuppression in experimental and clinical transplantation of various organs as well as in some diseases of autoimmune etiology. Among side effects of CsA, deleterious effect on male
reproductive
function is known to attributable to the decreased synthesis of testosterone, which is mainly produced by Leydig cells of testis.
Many efforts are being made to detect how CsA inhibits testosterone synthesis. One of the possible mechanism is direct toxic effect of CsA on Leydig cells.
Fosfomycin(FOM) is known to have cytoprotective effect from nephrotoxicity caused by CsA because the drug protects the lysosmal membrane integrity of renal tubular cells.
So this study was designed to observe the observe the changes of male reproductive organs induced by CsA, particularly those of Leydig cells and to know whether FOM could protect male reproductive organs from deleterious effects of CsA.
50 mature Sprague-Dawley rats were diveded into five groups with each 10 rats ; 1) Group I -control group treated with hormal saline. 2) Group Ⅱ-treated with FOM 400mg/kg/day. 3) Group Ⅲ-treated with CsA 30 mg/kg/day. 4) Group Ⅳ-treated with
CsA
30mg/kg/day and FOM 200mg/kg/day. 5) Group V-treated with CsA 30mg/kg/day and FOM 400mg/kg/day.
Treatments were made by daily intraperitoneal injection for 3 weeks. Body weights, reproductive organ weights, serum testosterone levels, and serum CsA levels were measured, and histologic and ultrastructural changes of testes were observed by
light and
electron microscopy.
@ES The results were as follows:
@EN All of the CsA-treated groups(group Ⅲ, Ⅳ, V) showed significant decrease in body weights and reproductive organ weights compared with control group(P<0.001 in body weights, P<0.05 in reproductive organ weights), and there were no
statistical
differences between CsA-treated groups.
2. Group Ⅲ and group Ⅳshowed decreased serum testosterone levels(P<0.001), atrophy of Leydig cells and degeneration of seminiferous tubules on light microscopic examinations of testes, and decreased densities of mitochondria and smooth
endoplasmic
reticulum with increased number and size of lipid droplets on electron microscopic examinations of Leydig cells.
3. The simultaneous administration of 400mg/kg of FOM with CsA(group) could protect Leydig cells histologically and somewhat adeliorate the decreased male reproductive function by alleviating the decrease in serum testosterone and the
degeneration
of
seminiferous tubules without alteration of serum CsA concentration.
These results suggest that the decreased testosterone synthesis, the possible cause of impaired male reproductive function induced by CsA, is attributable to the decrease in mitochondria and smooth endoplasmic reticulum, the organelles containing
the
enzymes of testosterone synthesis in Leyding cells, and the protective effect of FOM was regarded to be a cytoprotective effect from direct cytotoxicity of CsA.
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