Comparative renal, hepatic, and bone marrow toxicity of Cisplatin and radioactive Cisplatin (191Pt) in Wistar rats.
The aim of the study was to investigate the possibility to increase the therapeutic gain of the cytotoxic agent, cisplatin, by incorporation of radioactive platinum. In this study, we investigated how organs at risk (i.e., kidneys, bone marrow, and liver) are affected by treatment with 191Pt-cisplatin, compared to treatment with conventional cisplatin. Rats (total, n = 69) were divided into three groups and given 5 mg/kg 191Pt-cisplatin and 5 mg/kg nonradioactive cisplatin or saline. The weight of the animals and blood samples, including analysis of creatinine, bilirubin, alanine and aspartate aminotransferases and platelet count, was followed for 6 weeks after treatment. Histopathology examinations of kidney and liver tissues were performed. An initial decrease in weight gain was seen from 3 days after treatment with cisplatin and 191Pt-cisplatin and for 1 week onward; thereafter, the weight gain continued, following the same pattern as for the control group. Concentration of plasma creatinine was increased for both cisplatin groups but with no significant difference between treatment groups. No other significant differences in effect parameters were found. There was no increase in toxicity for radioactive cisplatin on liver, kidneys, and bone marrow, compared to conventional cisplatin. Further experimental and clinical studies on preparations of this type are thus warranted.
Norrgren
Kristina
K
Department of Radiation Physics, Malmö University Hospital, Malmö, Sweden. Kristina.Norrgren@med.lu.se
Sjölin
Maria
M
Björkman
Sven
S
Areberg
Johan
J
Johnsson
Anders
A
Johansson
L
L
Mattsson
Sören
S
D000818:Animals; D001855:Bone Marrow Diseases / Q000139:chemically induced; D056486:Chemical and Drug Induced Liver Injury; D002945:Cisplatin / Q000633:toxicity*; D005260:Female; D007674:Kidney Diseases / Q000139:chemically induced; D010984:Platinum / Q000633:toxicity*; D011868:Radioisotopes / Q000633:toxicity*; D011897:Random Allocation; D051381:Rats; D017208:Rats, Wistar
D011868:Radioisotopes; D010984:Platinum; D002945:Cisplatin