Comparison of the effects of bischolylglycinatechloro-platinum(II) versus cisplatin on liver regeneration after partial hepatectomy

Background: Regional Chemotherapy by intraportal administration has been en visaged as a useful strategy to prevent the high rate of recurrence after s urgical removal of single liver tumors, even though it may inhibit liver re generation. New cytostatic drugs, such as Bamet-H2 -Na[Pt(cholylglycinate-O ,N) (cholylglycinate-O) Cl]- have been developed to enhance the liver organ otropism of antiproliferative agents. The aim of the present study was to c ompare the effects of Bamet-H2 and cisplatin on liver regeneration. Materia ls and Methods: The ability of both drugs to inhibit liver cell proliferati on was investigated using rat hepatocytes in primary culture. Two-thirds pa rtially hepatectomized mice were used to measure the effects of glycocholic acid, cisplatin and Bamet-H2 on DNA synthesis by the regenerating liver in vivo. Results: Up to 300 mu M glycocholic acid, no effect on the growth of rat hepatocytes in primary culture was observed. By contrast, similar dose -dependent in vitro cytostatic effects of cisplatin and Bamet-H2 were found No effect on mouse liver regeneration was found in animals receiving glyco cholic acid. By contrast, both cisplatin and Bamet-H2 were found to induce a significant inhibition of DNA synthesis and slower recovery of liver mass . The effect of cisplatin was significantly stronger than that induced by B amet-H2. Differences between these two compounds were also observed regardi ng the content of the drug in several tissues at short- and mid-term. Both drugs were highly concentrated in the liver and kidney, with minor distribu tion in other tissues at 8 hours after the last injection of the drug. Howe ver, Bamet-H2 was more efficiently eliminated from the body in 5 days. More over, higher toxicity and lower survival were observed in the group of anim als treated with cisplatin as compared to Bamet-H2. Conclusions: Our result s indicate that in agreement with the previously reported effects on severa l tumor cells lines, cisplatin and Bamet-H2 are similarly efficient as cyto static drugs in liver cells when these are continuously exposed to the comp ounds in vitro. However, in the in vivo situation Bamet-H2 is better tolera ted by the animals and induces less inhibition of liver regeneration than c isplatin. This is probably due to the enhanced biliary elimination of Bamet -H2.