Korean Journal of Nephrology 1994;13(1):42-52.

Thyroxine의 Cisplaatin 신독성에 대한 효과

박용훈 , 김정욱 , 신손문

Abstract

This study was conducted to test the hypothesis that thyroxine has a protective effect on renal tubular injury induced by cisplatin (cis-diamminedichloroplatinum II). The changes in renal function, electrolyte concentra- tions, renal cortical Na', K' ATPase activity and alkaline phosphatase activity were measured in Sprague -Dawley rats divided into four groups. Seven normal (THY) and 7 cisplatin treated rats (CIS-THY) received thyroxine (10 mg/100g of body weight/dose SC). Seven additional cisplatin treated (CIS) and 11 normal control rats (NC) served as controls. Thyrox- ine was given daily for 7 days in THY and for 12 days from 7 days prior to the administration of cisplatin until 5 days after cisplatin administration in CIS-THY group. Cisplatin nephrotoxicity was induced by intraperitoneal administration of 5 mg/kg single dose of cisplatin. Na', K+ ATPase activity (pmole Pi/mg protein/hr) was decreased in CIS (20.8±4.6) compared with NC group (31.4±5.2, p<0.01). Contrarily, the enzyme activity was increased in THY (42.9±3.0, p<0.01) and CIS -THY (41.7±7.7, p<0.05) groups, Alkaline phosphatase activity (pmole Pi/mg protein/hr) was decreased in CIS (2.6±0.8, p<0.01) and thyroxine treated THY (2.8±1.0, p<0.05) and CIS-THY (3.1±0.9, p<0.05) compared with NC group (4.2±1.1). Nephrotoxicity was assessed by measuring serum BUN, creatinine and electrolytes. Serum BUN (mg/dl) and creatinine levels (mg/dl) were increased in CIS (144. 2±44.4 and 5.0+2.7) compared witb NC group (21.4±6. 0 and 0.9±0.3, p<0.01). However, serum BUN and creatinine levels were unchanged in THY (18.1±2.7 and 0.7+0.1) and CIS-THY (18.7±3.8 and 0.7±0.1) groups. The electrolytes were comparable in all four groups. Free thyroxine level (ng/dl) was decreased insignificantly in CIS (9.36±1.65) but were increased in thyroxine treated THY (36.64±3.45) and CIS-THY (30. 55±7.32) compared with NC group (14.34±4.77, p<0.01). These data indicates that thyroxine protect the kidney from cisplatin-induced nephrotoxicity by enhancing renal cortical Na', K' ATPase activity.