Effect of some anticancer drugs and combined chemotherapy on renal toxicity.
The nephrotoxic action of anticancer drugs such as nitrogranulogen (NG), methotrexate (MTX), 5-fluorouracil (5-FU) and cyclophosphamide (CY) administered alone or in combination [MTX + 5-FU + CY (CMF)] was evaluated in experiments on Wistar rats. After drug administration, creatinine concentrations in the plasma and in the urine of the rats were determined, as well as creatinine clearance. Histopathologic evaluation of the kidneys was also performed. After MTX administration a significant increase (p = 0.0228) in the plasma creatinine concentration and a significant (p = 0.0001) decrease in creatinine clearance was noted compared to controls. After the administration of NG, 5-FU and CY neither a statistically significant increase in creatinine concentration nor an increase in creatinine clearance was observed compared to the group receiving no cytostatics. Following polytherapy according to the CMF regimen, a statistically significant decrease (p = 0.0343) in creatinine clearance was found, but creatinine concentration did not increase significantly compared to controls. CY caused hemorrhagic cystitis in 40% of rats, but it did not cause this complication when combined with 5-FU and MTX. Histologic changes were found in rat kidneys after administration of MTX, CY and NG, while no such change was observed after 5-FU and joint administration of MTX + 5-FU + CY compared to controls. Our studies indicate that nephrotoxicity of MTX + 5-FU + CY administered jointly is lower than in monotherapy.
Skretkowicz
J
J
Department of Pharmacology, Medical University of Lodz, Poland.
Sekulska
M
M
Danilewicz
M
M
Wagrowska-Danilewicz
M
M
Polakowski
P
P
D000818:Animals; D000971:Antineoplastic Combined Chemotherapy Protocols / Q000633:toxicity*; D003404:Creatinine / Q000097:blood / Q000652:urine; D003520:Cyclophosphamide / Q000633:toxicity*; D003556:Cystitis / Q000139:chemically induced; D005472:Fluorouracil / Q000633:toxicity*; D005919:Glomerular Filtration Rate / Q000187:drug effects; D006470:Hemorrhage / Q000139:chemically induced; D007668:Kidney / Q000187:drug effects*; D008466:Mechlorethamine / Q000633:toxicity*; D008727:Methotrexate / Q000633:toxicity*; D051381:Rats; D017208:Rats, Wistar
D008466:Mechlorethamine; D003520:Cyclophosphamide; D003404:Creatinine; D005472:Fluorouracil; D008727:Methotrexate