Toxicological Research

Korean Society of Toxicology & Korea Environmental Mutagen Society (한국독성학회)
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Subacute Toxicity of cis-Malonato[(4R,5R)-4,5-bis(aminomethyl)-2-isopropyl-1,3-dioxolane]platinum(II)(SKI 2053R) in rats

랫드에서 cis-Malonato[(4R,5R)-4,5-bis(aminomethyl)-2-isopropyl-1,3-dioxolane]platinum(II)(SKI 2053R)의 아급성독성시험에 관한 연구

  • Kim, Hyoung-Ook (College of Veterinary Medicine, Seoul National University) ;
  • Kang, Kyung-Sun (College of Veterinary Medicine, Seoul National University) ;
  • Shin, Dong-Jin (College of Veterinary Medicine, Seoul National University) ;
  • Cho, Jae-Jin (College of Veterinary Medicine, Seoul National University) ;
  • Kim, Bae-Hwan (College of Veterinary Medicine, Seoul National University) ;
  • Seo, Kwang-Won (College of Veterinary Medicine, Seoul National University) ;
  • Nam, Ki-Hoan (College of Veterinary Medicine, Seoul National University) ;
  • Lee, Yong-Soon (College of Veterinary Medicine, Seoul National University)
  • 김형욱 (서울대학교 수의과대학 공중보건학교실) ;
  • 강경선 (서울대학교 수의과대학 공중보건학교실) ;
  • 신동진 (서울대학교 수의과대학 공중보건학교실) ;
  • 조재진 (서울대학교 수의과대학 공중보건학교실) ;
  • 김배환 (서울대학교 수의과대학 공중보건학교실) ;
  • 서광원 (서울대학교 수의과대학 공중보건학교실) ;
  • 남기환 (서울대학교 수의과대학 공중보건학교실) ;
  • 이영순 (서울대학교 수의과대학 공중보건학교실)
  • Published : 1992.12.01
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Abstract

This study was performed to determine the toxic effects of graded dose levels of SKI 2053R after repeated administration. Three groups of Sprague-Dawley rats(10M and 10F per group) were given a total of 25 i.v. injections of SKI 2053R (1.50,3.75,9.38mg/kg/day). In order to compare the toxic effects of SKI 2053R with those of cisplatin, one group of Sprague-Dawley rats (10M and 10F per group) were given a total of 25 i.v.injections of cisplatin (1.70mg/kg/day). The dosing schedule was divided into five courses of 5 consecutive days with 16-day dose-free intervals between each course. No drug-related toxicity occurred in low dose level group (1.50mg/kg/day) of SKI2053R. From the results of hematological examination, peripheral WBC counts, RBC counts and hemoglobin of high dose level group(9.38mg/kg/day)of SKI 2053R were significantly lower than those of no-treated group. Other toxicities including reduced final body weight, proteinuria and hematuria were observed in high dose level group of SKI 2053R. But, no change was detected in serum biochemical values of SKI 2053R treated groups. All of the rats in cisplatin treated group were died between 3 and 13 weeks, while rats treated with SKI2053R survived to the end except one rat of middle dose level group(3.75mg/kg/day). In histopathological examinations, rats that received cisplatin manifested severe tubular damage in kidney and hemosiderosis in spleen, but no critical pathological lesion was observed in rats of other groups. Considering the results of this study, it was concluded that non-toxic dose of SKI 2053R in this treatment schedule was estimated to be 3.75 mg/kg/day and the maximum tolerated dose was to be higher than 9.38mg/kg/day. The toxic profiles fo SKI 2053R were different from those of cisplatin, and its toxicity was considerably lower than that of cisplatin.

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