Interaction of cis-diamminedichloroplatinum and renal irradiation on renal function in the young and adult rat. 1987

H T Jongejan, and A J van der Kogel, and A P Provoost, and J C Molenaar
Department of Paediatric Surgery, Erasmus University Rotterdam, The Netherlands.

The interaction between single low doses of cis-diamminedichloroplatinum(II) (c-DDP) and renal irradiation (7.5, 10, 12.5 Gy) on renal function and systolic blood pressure (SBP) was investigated in young (3-4 weeks old, BW 45-65 g) and adult rats (over 12 weeks old, BW 230-290 g). The glomerular filtration rate (GFR) and effective renal plasma flow (ERPF), plasma creatinine, urea and SBP were measured over 24 weeks. Changes in ERPF, plasma creatinine and urea concentrations paralleled GFR changes, but tended to be less pronounced. In young rats, BW and GFR were 10-20% below control values after c-DDP administration (5 mg/kg BW). Irradiation caused a dose-dependent drop in GFR, starting 4 weeks after irradiation in young rats. When c-DDP was given immediately after irradiation to the young rats, the loss of renal function was more pronounced than after either treatment modality alone. Dose-effect curves for a greater than 25% reduction of the GFR relative to controls (ml/min) after 24 weeks gave an ED50 of 9.8 Gy for irradiation alone and 4.6 Gy for irradiation followed by c-DDP. After correction for the drug effect, dose-effect curves were similar for renal irradiation given alone or followed by c-DDP administration in young rats. In adult rats, c-DDP (2.5 mg/kg BW) or irradiation alone did not significantly alter renal function during the follow-up period. Only 12.5 Gy in combination with c-DDP, caused a significant reduction in GFR after 16 weeks in adult rats. In adult rats data were too limited for probit analysis.(ABSTRACT TRUNCATED AT 250 WORDS)

UI MeSH Term Description Entries
D007668 Kidney Body organ that filters blood for the secretion of URINE and that regulates ion concentrations. Kidneys
D007677 Kidney Function Tests Laboratory tests used to evaluate how well the kidneys are working through examination of blood and urine. Function Test, Kidney,Function Tests, Kidney,Kidney Function Test,Test, Kidney Function,Tests, Kidney Function
D008297 Male Males
D011833 Radiation Injuries, Experimental Experimentally produced harmful effects of ionizing or non-ionizing RADIATION in CHORDATA animals. Experimental Radiation Injuries,Injuries, Experimental Radiation,Experimental Radiation Injury,Radiation Injury, Experimental
D011919 Rats, Inbred Strains Genetically identical individuals developed from brother and sister matings which have been carried out for twenty or more generations or by parent x offspring matings carried out with certain restrictions. This also includes animals with a long history of closed colony breeding. August Rats,Inbred Rat Strains,Inbred Strain of Rat,Inbred Strain of Rats,Inbred Strains of Rats,Rat, Inbred Strain,August Rat,Inbred Rat Strain,Inbred Strain Rat,Inbred Strain Rats,Inbred Strains Rat,Inbred Strains Rats,Rat Inbred Strain,Rat Inbred Strains,Rat Strain, Inbred,Rat Strains, Inbred,Rat, August,Rat, Inbred Strains,Rats Inbred Strain,Rats Inbred Strains,Rats, August,Rats, Inbred Strain,Strain Rat, Inbred,Strain Rats, Inbred,Strain, Inbred Rat,Strains, Inbred Rat
D012079 Renal Circulation The circulation of the BLOOD through the vessels of the KIDNEY. Kidney Circulation,Renal Blood Flow,Circulation, Kidney,Circulation, Renal,Blood Flow, Renal,Flow, Renal Blood
D001794 Blood Pressure PRESSURE of the BLOOD on the ARTERIES and other BLOOD VESSELS. Systolic Pressure,Diastolic Pressure,Pulse Pressure,Pressure, Blood,Pressure, Diastolic,Pressure, Pulse,Pressure, Systolic,Pressures, Systolic
D002945 Cisplatin An inorganic and water-soluble platinum complex. After undergoing hydrolysis, it reacts with DNA to produce both intra and interstrand crosslinks. These crosslinks appear to impair replication and transcription of DNA. The cytotoxicity of cisplatin correlates with cellular arrest in the G2 phase of the cell cycle. Platinum Diamminodichloride,cis-Diamminedichloroplatinum(II),cis-Dichlorodiammineplatinum(II),Biocisplatinum,Dichlorodiammineplatinum,NSC-119875,Platidiam,Platino,Platinol,cis-Diamminedichloroplatinum,cis-Platinum,Diamminodichloride, Platinum,cis Diamminedichloroplatinum,cis Platinum
D003404 Creatinine Creatinine Sulfate Salt,Krebiozen,Salt, Creatinine Sulfate,Sulfate Salt, Creatinine
D004307 Dose-Response Relationship, Radiation The relationship between the dose of administered radiation and the response of the organism or tissue to the radiation. Dose Response Relationship, Radiation,Dose-Response Relationships, Radiation,Radiation Dose-Response Relationship,Radiation Dose-Response Relationships,Relationship, Radiation Dose-Response,Relationships, Radiation Dose-Response

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