Toxicological and Tumoricidal Evaluations of a New Platinum Complex, (–)‐(R)‐2‐Aminomethy lpyrrolidine (1,1‐cyclobutanedicarboxylato) platinum (II) Monohydrate, in Rats
Autor: | Hiroki Mitsui, Kazumi Morikawa, Tomoko Matsumoto, Koichi Endo, Kenichi Akamatsu, Masuo Koizumi, Kinya Koizumi |
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Jazyk: | angličtina |
Rok vydání: | 1991 |
Předmět: |
Male
Cancer Research medicine.medical_treatment Antineoplastic Agents Pharmacology Article Nephrotoxicity Carboplatin chemistry.chemical_compound Structure-Activity Relationship medicine Animals Carcinoma 256 Walker Blood urea nitrogen Cisplatin Chemotherapy Toxicity business.industry Lethal dose Rats Inbred Strains Rats Oncology chemistry Immunology Platinum Compound Rat business medicine.drug Antitumor platinum complex |
Zdroj: | Japanese Journal of Cancer Research : Gann |
ISSN: | 1876-4673 0910-5050 |
Popis: | The toxicities and antitumor activity of a new anticancer platinum compound, (-)-(R)-2-aminomethylpyrrolidine(1,1-cyclobutanedicarboxylato++ +) platinum(II) monohydrate (DWA2114R), were examined in rats by single intravenous injection in comparison with those of cis-diammine(1,1-cyclobutanedicarboxylato)platinum(II) (CBDCA) and cis-diamminedichloroplatinum(II) (CDDP). The lethal dose (LD) of DWA2114R (100 mg/kg) or CBDCA (80 mg/kg) caused a slight decrease in body weight (less than 10%) and no significant change in the levels of blood urea nitrogen and urinary sugar and protein. In contrast, a sub-LD level of CDDP (8 mg/kg) seriously decreased body weight (20%) and markedly elevated the levels of these nephrotoxicity parameters. Monitoring the numbers of peripheral blood cells for 3 weeks after the drug injection revealed that all three drugs showed severe thrombocytopenia, moderate leukopenia and slight anemia. However, CBDCA induced the most severe thrombocytopenia among these drugs. The number of platelets was reduced by 60% in rats injected with a half LD of CBDCA. A moderate reduction in platelet count (35-43%) was caused by an equitoxic dose of DWA2114R or CDDP, but abated about 3 days faster than that caused by CBDCA. Interestingly, only CDDP caused an irreversible anemia. Each drug showed a potent antitumor activity at weakly toxic doses against Walker 256 carcinosarcoma transplanted intramuscularly into rats. These results indicate that DWA2114R could be a promising new platinum anticancer agent with an improved toxicity profile. |
Databáze: | OpenAIRE |
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