Early use of cisplatin is safe after partial hepatectomy.
Although cisplatin is widely used in the treatment of liver tumors, little information is available concerning its effect on liver regeneration. This report evaluates the effect of cisplatin on liver regeneration after hepatectomy (HPx). One hundred sixty male Sprague-Dawley rats were placed into five experimental groups following 70% hepatectomy. Group I (untreated controls, n = 32) received 0.9% saline intraperitoneally (IP); group II (n = 31), cisplatin 4 mg/kg IP; group III (n = 36), cisplatin 10 mg/kg IP; group IV (n = 34), cisplatin 20 mg/kg IP; and group V (n = 27), doxorubicin 6 mg/kg intravenously (IV). Five additional sham groups underwent celiotomy without hepatectomy (n = 106) followed by the above treatment protocols. Liver regeneration was evaluated by liver weight, DNA incorporation measured by tritiated thymidine (3H-TdR), and quantitative image analysis (QIA) of hepatic nuclei at 18, 24, 36, 48, and 72 hours, and 5 days postoperatively. 3H-TdR incorporation peaked at 36 hours and was similar in hepatectomized controls group I (404 +/- 110 counts per minute [CPM]/mg liver weight) and cisplatin-treated rats (groups II to IV) (P > .05, ANOVA). All sham groups were similar to controls. QIA of feulgen-stained touch preps identified polyploid, stem line, and proliferating nuclei in both controls and treated groups. At 36 hours, QIA showed differences in mitotic status of sham, control, and adriamycin-treated HPx rats, consistent with 3H-TdR incorporation. In contrast, although cisplatin-treated rats receiving 4 mg/kg showed proliferating nuclei, QIA demonstrated decreasing hepatocyte proliferation with higher doses of cisplatin (10 mg/kg, and 20 mg/kg).(ABSTRACT TRUNCATED AT 250 WORDS)
Engum
S A
SA
Department of Surgery, Indian University School of Medicine, Indianapolis.
Sidner
R A
RA
Miller
G A
GA
Galliani
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C
Grosfeld
J L
JL
D000818:Animals; D002455:Cell Division; D002945:Cisplatin / Q000494:pharmacology*; D004317:Doxorubicin / Q000494:pharmacology*; D004353:Drug Evaluation, Preclinical; D006498:Hepatectomy / Q000401:mortality; D008099:Liver / Q000033:anatomy & histology / Q000166:cytology / Q000187:drug effects* / Q000601:surgery; D008115:Liver Regeneration / Q000187:drug effects*; D008297:Male; D009929:Organ Size; D011182:Postoperative Care; D011897:Random Allocation; D051381:Rats; D017207:Rats, Sprague-Dawley; D012709:Serum Albumin / Q000187:drug effects; D015996:Survival Rate; D013997:Time Factors
D012709:Serum Albumin; D004317:Doxorubicin; D002945:Cisplatin