Biomedical subjects

S Kerpel-Fronius

Publications and source records attributed to S Kerpel-Fronius.

75 records · Page 5Linked to original sources

PubMedDate not supplied

Evaluation of side effects of platinum complexes (CDDP, CBDCA, CHIP) on rat bone marrow.

The in vivo toxic actions of cis-dichloro-1, 1-cyclo-butane-dicarboxylate platinum (II): carboplatin (CBDCA), cis-diisopropyl-ammine-transdihydroxy-dichloro platinum (IV) and iproplatin (CHIP) were compared with those of cis-diamminedichloroplatinum (II): cisplatin (CDDP) on rat bone marrow. To elucidate the biochemical basis of side effects of platinum analogs, the protein and DNA content, thymidine kinase (TK) EC 2.7.1.21 activity and cellularity (MNC) were measured from the femoral bone marrow at 48 hours after i.v. single injection of these three compounds using equitoxic doses as fraction of LD50 (CDDP: 9, CHIP: 50, CBDCA: 80 mg/kg). Dose response studies showed that each drug depressed in dose dependent fashion the cellularity, DNA content and TK activity. As the I50 values indicated, the CHIP caused the most toxic effect in the bone marrow and the influence of CBDCA was the least. The nadir of biochemical alterations was observed 24-48 hours after drug administration. The recovery of bone marrow was completed 96 hours after the treatment.

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PubMedDate not supplied

Comparison of tumor growth inhibitory and toxic effects of a new fluorouracil--nitrosourea derivative (B-3839).

The toxic effect and anti-tumor activity of B-3839, a new molecular combination of pyrimidine antimetabolite 5-fluorouracil (5-FU) with the alkylating agent N-Chloroethyl-N-nitrosourea (BCNU), was compared to that of BCNU and 5-FU given alone and in physical combination. The tumor inhibitory effect of B-3839 was similar to that of BCNU given alone or combined with a low dose of 5-FU in the i.m. Walker tumor model. Furthermore, the bone marrow toxicity of BCNU was not significantly altered by either form of combination with 5-FU. The intestinal side effects, evaluated by measuring the decrease of marker enzyme (thymidine kinase, xanthine oxidase, alkaline phosphatase, sucrase, maltase) activities in isolated enterocytes, were dose-dependent and moderate. A significant, more than 30%, decrease occurred only if BCNU and 5-FU were given simultaneously or as B-3839. The molecular combination of the two drugs does not provide any additional advantage over their physical combination.

Animals↗

PubMedDate not supplied

Enzymological and morphological changes in rat intestinal mucosa following treatment with alkylating sugar alcohol derivatives.

Wistar rats were treated with alkylating sugar alcohol derivatives, dianhydrogalactitol (DAG) and diacetyldyanhydrogalactitol (Diac-DAG), respectively. The drugs were intravenously administered as a single, bolus injection. The applied doses 2.5, 5, 10, 17 mg/kg DAG and 5, 10, 20, 40 mg/kg Diac-DAG were roughly equitoxic. The effect of these cytostatic agents was studied on the different marker enzymes (thymidine kinase, xanthine oxidase, alkaline phosphatase, sucrase, maltase) of the separated mucosa cells derived from the functional and proliferating zone of the small intestine. Both DAG and Diac-DAG inhibited the enzyme activities of the proliferating and mature enterocytes in a dose dependent fashion, primarily acting on the crypt specific thymidine kinase. The time dependent sequence in the biochemical alterations correlated well with the cytomorphological changes. The drug-induced damage was most pronounced 48 hours after a single treatment. The regeneration of the intestinal mucosa began on days 3 and 4 and was completed by day 7. Diac-DAG at equimolar concentration proved to be more toxic than DAG on the intestine as judged by the significantly higher decrease of protein content and xanthine oxidase activity.

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