Effect of Unilateral Renal Perfusion of Cyclosporine and Mitomycin on Rat's Kidney

Baek, Seung In; Lim, Hyun Suk; Shin, Weon Hye; Ko, Cheol Woo; Koo, Ja Hoon; Kwak, Jung Sik

J Korean Soc Pediatr Nephrol > Volume 2(2); 1998 > Article

J Korean Soc Pediatr Nephrol 1998;2(2): 138-144.

Cyclosporine과 Mitomycin의 일측성 신관류로 초래되는 백서 신병변에 관한 연구

백승인, 임현석, 신원혜, 고철우, 구자훈, 곽정식

¹경북대학교 의과대학 소아과학교실
²경북대학교 의과대학 소아과학교실
³경북대학교 의과대학 소아과학교실
⁴경북대학교 의과대학 소아과학교실
⁵경북대학교 의과대학 소아과학교실
⁶경북대학교 의과대학 병리학교실

Effect of Unilateral Renal Perfusion of Cyclosporine and Mitomycin on Rat's Kidney

Seung In Baek, Hyun Suk Lim, Weon Hye Shin, Cheol Woo Ko, Ja Hoon Koo, Jung Sik Kwak

¹Department of Pediatrics, Kyungpook National University, School of Medicine
²Department of Pediatrics, Kyungpook National University, School of Medicine
³Department of Pediatrics, Kyungpook National University, School of Medicine
⁴Department of Pediatrics, Kyungpook National University, School of Medicine
⁵Department of Pediatrics, Kyungpook National University, School of Medicine
⁶Department of Pathology, Kyungpook National University, School of Medicine

ABSTRACT

Purpose : The use of cyclosporine and mitomycin in various immunologic or neoplastic disorders has been known to cause wide-ranged nephrotoxic effects including thrombotic microangiopathy. However, the mechanism of nephrotoxicity of these drugs has not been studied adequately, so that present experimental study has been undertaken to find out whether these drugs can cause direct damage to the kidney and to clarify the pathogenetic mechanism of nephrotoxic effect of these drugs. Materials and methods : Sprague-Dawley rats weighing 250-300 gm were used for experimental animals and unilateral renal perfusion technique, modified from the method described by Hoyer et al was used. Isolation of left kidney from systemic circulation was made by clamping aorta and left renal vein and a hole was punctured in the anterior wall of the left renal vein. Cyclosporine (2.5 mg in 4 ml solution) and mitomycin (1.6 mg in 4ml solution) were infused through left renal artery and normal saline was used in control rats. Forty-eight hours after infusion of the drugs, animals were sacrificed and left kidney removed and processed for histologic examination. Total ischemic time of left kidney was less than 15 minutes:
Results : Cyclosporine-perfused group showed severe swelling of glomerular endothelial ceil along with swelling of glomerular epithelial cell and interstitial vascular endothelial cell. Mitomycin-perfused group also showed severe swelling of glomerular endothelial and epithelial cells. And in addition to these findings, they demonstrated platelets aggregation, swelling and degranulation of platelets and fibrin accumulation in some of the capillaries, indicating occurrance of thrombotic microangiopathy.
Conclusion : present experiment indicates that cyclosporine and mitomycin can cause direct toxic injury to renal endothelial cell. And this direct toxic damage to endothelial cell seems to be an important initiating event for the development of thrombotic microangiopathy.

Key words: Nephrotoxicity | Cyclosporine | Mitomycin | Thrombotic microangiopathy