Comparative nephrotoxicity of cisplatin and new octahedral Pt(IV) complexes

Won Kyu Kim, Young Ee Kwon

Research output: Contribution to journalArticle

10 Citations (Scopus)

Abstract

Purpose: Previously, we have reported that the newly synthesized octahedral Pt(IV) compound, trans,cis-Pt(acetato)2Cl2(1,4- butanediamine), K101 and trans,cis-Pt(trifluoroacetato)2Cl 2(1,4-butanediamine), K102 showed potent antitumor activities in vitro and in vivo. In order to compare the nephrotoxicity of the newly synthesized Pt(IV) complexes, K102 and K102 with cisplatin, we performed various tests. Materials and methods: We performed a single dose acute toxicity test for LD50 values determination, biochemical assays in blood serum, acid phosphatase enzyme histochemistry and transmission electron microscopic studies in renal proximal tubular cells in mice in vivo. The route of drugs administration is intraperitoneal injection. Results: In biochemical assays, the serum levels of BUN were significantly elevated at 6 h (p < 0.001), 1 day (p < 0.05) and 3 days (p < 0.001) after injection in cisplatin treated mice (6 mg/kg, single dose, i.p.). On the other hand, the serum levels of BUN were slightly elevated at 6 h (p < 0.01) only in K101 treated mice (8.2 mg/kg, single dose, i.p.), and were significantly raised at 6 h, 1 and 3 days (p < 0.05) after injection in K102 treated mice (6.2 mg/kg, single dose, i.p.). The higher serum BUN level in K102 treated mice is considered that K102 possesses more lipophilic fluoro group than acetyl group in K101. The values of creatinine and uric acid were similar in all groups. The ultrastructural morphological changes of K101- or K102-administrated mice were less remarkable than cisplatin-administrated mice. In acid phosphatase enzyme histochemistry, cisplatin treatment induced relevant changes in the distribution pattern of enzyme activity compared with K101 or K102 treatment at 7 days after injection. Conclusions: In conclusion, these results show that K101 is less nephrotoxic than cisplatin and a promising new platinum complex.

Original languageEnglish
Pages (from-to)237-243
Number of pages7
JournalCancer Chemotherapy and Pharmacology
Volume60
Issue number2
DOIs
StatePublished - 2007 Jul 1

Fingerprint

Cisplatin
Blood Urea Nitrogen
Acid Phosphatase
Assays
Serum
Injections
Enzymes
Enzyme activity
Drug Administration Routes
Acute Toxicity Tests
Uric Acid
Platinum
Toxicity
Creatinine
Lethal Dose 50
Blood
Intraperitoneal Injections
Electrons
Pharmaceutical Preparations
Kidney

Keywords

  • Acid phophatase activity
  • Cisplatin
  • K101
  • K102
  • Nephrotoxicity
  • Octahedral Pt(IV) complex
  • Ultrastructure

Cite this

@article{5d90b1ba39004032af9aa8e6f69fcf8f,
title = "Comparative nephrotoxicity of cisplatin and new octahedral Pt(IV) complexes",
abstract = "Purpose: Previously, we have reported that the newly synthesized octahedral Pt(IV) compound, trans,cis-Pt(acetato)2Cl2(1,4- butanediamine), K101 and trans,cis-Pt(trifluoroacetato)2Cl 2(1,4-butanediamine), K102 showed potent antitumor activities in vitro and in vivo. In order to compare the nephrotoxicity of the newly synthesized Pt(IV) complexes, K102 and K102 with cisplatin, we performed various tests. Materials and methods: We performed a single dose acute toxicity test for LD50 values determination, biochemical assays in blood serum, acid phosphatase enzyme histochemistry and transmission electron microscopic studies in renal proximal tubular cells in mice in vivo. The route of drugs administration is intraperitoneal injection. Results: In biochemical assays, the serum levels of BUN were significantly elevated at 6 h (p < 0.001), 1 day (p < 0.05) and 3 days (p < 0.001) after injection in cisplatin treated mice (6 mg/kg, single dose, i.p.). On the other hand, the serum levels of BUN were slightly elevated at 6 h (p < 0.01) only in K101 treated mice (8.2 mg/kg, single dose, i.p.), and were significantly raised at 6 h, 1 and 3 days (p < 0.05) after injection in K102 treated mice (6.2 mg/kg, single dose, i.p.). The higher serum BUN level in K102 treated mice is considered that K102 possesses more lipophilic fluoro group than acetyl group in K101. The values of creatinine and uric acid were similar in all groups. The ultrastructural morphological changes of K101- or K102-administrated mice were less remarkable than cisplatin-administrated mice. In acid phosphatase enzyme histochemistry, cisplatin treatment induced relevant changes in the distribution pattern of enzyme activity compared with K101 or K102 treatment at 7 days after injection. Conclusions: In conclusion, these results show that K101 is less nephrotoxic than cisplatin and a promising new platinum complex.",
keywords = "Acid phophatase activity, Cisplatin, K101, K102, Nephrotoxicity, Octahedral Pt(IV) complex, Ultrastructure",
author = "Kim, {Won Kyu} and Kwon, {Young Ee}",
year = "2007",
month = "7",
day = "1",
doi = "10.1007/s00280-006-0366-7",
language = "English",
volume = "60",
pages = "237--243",
journal = "Cancer Chemotherapy and Pharmacology",
issn = "0344-5704",
number = "2",

}

Comparative nephrotoxicity of cisplatin and new octahedral Pt(IV) complexes. / Kim, Won Kyu; Kwon, Young Ee.

In: Cancer Chemotherapy and Pharmacology, Vol. 60, No. 2, 01.07.2007, p. 237-243.

Research output: Contribution to journalArticle

TY - JOUR

T1 - Comparative nephrotoxicity of cisplatin and new octahedral Pt(IV) complexes

AU - Kim, Won Kyu

AU - Kwon, Young Ee

PY - 2007/7/1

Y1 - 2007/7/1

N2 - Purpose: Previously, we have reported that the newly synthesized octahedral Pt(IV) compound, trans,cis-Pt(acetato)2Cl2(1,4- butanediamine), K101 and trans,cis-Pt(trifluoroacetato)2Cl 2(1,4-butanediamine), K102 showed potent antitumor activities in vitro and in vivo. In order to compare the nephrotoxicity of the newly synthesized Pt(IV) complexes, K102 and K102 with cisplatin, we performed various tests. Materials and methods: We performed a single dose acute toxicity test for LD50 values determination, biochemical assays in blood serum, acid phosphatase enzyme histochemistry and transmission electron microscopic studies in renal proximal tubular cells in mice in vivo. The route of drugs administration is intraperitoneal injection. Results: In biochemical assays, the serum levels of BUN were significantly elevated at 6 h (p < 0.001), 1 day (p < 0.05) and 3 days (p < 0.001) after injection in cisplatin treated mice (6 mg/kg, single dose, i.p.). On the other hand, the serum levels of BUN were slightly elevated at 6 h (p < 0.01) only in K101 treated mice (8.2 mg/kg, single dose, i.p.), and were significantly raised at 6 h, 1 and 3 days (p < 0.05) after injection in K102 treated mice (6.2 mg/kg, single dose, i.p.). The higher serum BUN level in K102 treated mice is considered that K102 possesses more lipophilic fluoro group than acetyl group in K101. The values of creatinine and uric acid were similar in all groups. The ultrastructural morphological changes of K101- or K102-administrated mice were less remarkable than cisplatin-administrated mice. In acid phosphatase enzyme histochemistry, cisplatin treatment induced relevant changes in the distribution pattern of enzyme activity compared with K101 or K102 treatment at 7 days after injection. Conclusions: In conclusion, these results show that K101 is less nephrotoxic than cisplatin and a promising new platinum complex.

AB - Purpose: Previously, we have reported that the newly synthesized octahedral Pt(IV) compound, trans,cis-Pt(acetato)2Cl2(1,4- butanediamine), K101 and trans,cis-Pt(trifluoroacetato)2Cl 2(1,4-butanediamine), K102 showed potent antitumor activities in vitro and in vivo. In order to compare the nephrotoxicity of the newly synthesized Pt(IV) complexes, K102 and K102 with cisplatin, we performed various tests. Materials and methods: We performed a single dose acute toxicity test for LD50 values determination, biochemical assays in blood serum, acid phosphatase enzyme histochemistry and transmission electron microscopic studies in renal proximal tubular cells in mice in vivo. The route of drugs administration is intraperitoneal injection. Results: In biochemical assays, the serum levels of BUN were significantly elevated at 6 h (p < 0.001), 1 day (p < 0.05) and 3 days (p < 0.001) after injection in cisplatin treated mice (6 mg/kg, single dose, i.p.). On the other hand, the serum levels of BUN were slightly elevated at 6 h (p < 0.01) only in K101 treated mice (8.2 mg/kg, single dose, i.p.), and were significantly raised at 6 h, 1 and 3 days (p < 0.05) after injection in K102 treated mice (6.2 mg/kg, single dose, i.p.). The higher serum BUN level in K102 treated mice is considered that K102 possesses more lipophilic fluoro group than acetyl group in K101. The values of creatinine and uric acid were similar in all groups. The ultrastructural morphological changes of K101- or K102-administrated mice were less remarkable than cisplatin-administrated mice. In acid phosphatase enzyme histochemistry, cisplatin treatment induced relevant changes in the distribution pattern of enzyme activity compared with K101 or K102 treatment at 7 days after injection. Conclusions: In conclusion, these results show that K101 is less nephrotoxic than cisplatin and a promising new platinum complex.

KW - Acid phophatase activity

KW - Cisplatin

KW - K101

KW - K102

KW - Nephrotoxicity

KW - Octahedral Pt(IV) complex

KW - Ultrastructure

UR - http://www.scopus.com/inward/record.url?scp=34248341435&partnerID=8YFLogxK

U2 - 10.1007/s00280-006-0366-7

DO - 10.1007/s00280-006-0366-7

M3 - Article

C2 - 17089165

AN - SCOPUS:34248341435

VL - 60

SP - 237

EP - 243

JO - Cancer Chemotherapy and Pharmacology

JF - Cancer Chemotherapy and Pharmacology

SN - 0344-5704

IS - 2

ER -