Comparison of intestinal toxic effects of platinum complexes: cisplatin (CDDP), carboplatin (CBDCA), and iproplatin (CHIP).
The biochemical background of the intestinal side effects of cis-diammine-1,1-cyclobutane dicarboxylate platinum (II) (CBDCA) and cis-diisopropylamine-trans-dihydroxy-dichloro platinum (IV) (CHIP) was compared with those of cis-diamminedichloroplatinum (II) (CDDP). Biochemical investigations were carried out on mucosal cells isolated by a combined chemical-mechanical method from the total length of the small intestine. After treatment with single, equitoxic doses of Pt analogues, the activities of thymidine kinase (TK) EC 2.7.1.21, sucrase (SUC) EC 3.2.1.26, maltase (MAL) EC 3.2.1.20, and protein content showed dose-dependent decreases, whereas the activity of alkaline phosphatase (AP) EC 3.2.1.20 increased slightly. The nadir of enzyme activity changes occurred 24-48 h after treatment. For the regeneration of the mucosa more than 96 h was necessary. Of the platinum analogues studied, CHIP proved to be the most toxic to the small intestine. While the highest doses of CDDP and CBDCA (0.66 x LD50) caused significant but less than 50% decreases in TK, SUC, MAL, and protein content (PROT), the CHIP doses needed for 50% reduction were between 0.44-0.66 x LD50.
Kralovánszky
J
J
National Institute of Oncology Budapest, Hungary.
Prajda
N
N
Kerpel-Fronius
S
S
Gál
F
F
Kiss
F
F
D000469:Alkaline Phosphatase / Q000032:analysis; D000818:Animals; D000970:Antineoplastic Agents / Q000633:toxicity*; D016190:Carboplatin; D002945:Cisplatin / Q000633:toxicity*; D004305:Dose-Response Relationship, Drug; D007413:Intestinal Mucosa / Q000187:drug effects* / Q000201:enzymology; D008297:Male; D009944:Organoplatinum Compounds / Q000633:toxicity*; D051381:Rats; D013937:Thymidine Kinase / Q000032:analysis
D000970:Antineoplastic Agents; D009944:Organoplatinum Compounds; C023359:iproplatin; D016190:Carboplatin; D013937:Thymidine Kinase; D000469:Alkaline Phosphatase; D002945:Cisplatin