Evaluation of kidney and liver subacute toxicity of antitumor agents using serum biochemical parameters in rats.
Hepatic and renal subacute toxicity induced by the antineoplastic drugs chlorambucil, cisplatin, epirubicin and methotrexate and the steroid alkylating agent 3 beta-hydroxy-13 alpha-amino-13,17-seco-5 alpha-androstan-17-oic-13, 17-lactam (p-[bis(2-chloroethyl) amino] phenyl) acetate was investigated in rats using serum biochemical parameters. Toxicological evaluation was performed in serum samples following the administration of dose regimens of the agents that were previously shown to be effective in suppressing malignant tumor growth or to prolong survival in tumor bearing animals. Hepatic and renal subacute toxicity was evaluated by measuring enzyme activity or concentrations of: alanine aminotransferase, alkaline phosphatase, aspartate aminotransferase, total cholesterol, gamma-glutamyltransferase, glucose, potassium, sodium, blood urea nitrogen and uric acid. The use of the above serum biochemical parameters indicated that the overall toxicity impact of the antitumor drugs was methotrexate < cisplatin < epirubicin < chlorambucil. The homo-azasteroid ester only transiently affected the biochemical parameters associated with renal toxicity, while it affected some of the biochemical parameters associated with hepatic toxicity, though to a significantly lower extent than the antitumor drugs.
Pispirigos
K
K
Department of Pharmaceutical Chemistry, School of Pharmacy, University of Patras, Greece.
Catsoulakos
P
P
Karakiulakis
G
G
D000410:Alanine Transaminase / Q000097:blood; D000469:Alkaline Phosphatase / Q000097:blood; D000818:Animals; D000970:Antineoplastic Agents / Q000633:toxicity*; D001219:Aspartate Aminotransferases / Q000097:blood; D001378:Azasteroids / Q000633:toxicity; D001786:Blood Glucose / Q000032:analysis; D056486:Chemical and Drug Induced Liver Injury; D002699:Chlorambucil / Q000633:toxicity; D002784:Cholesterol / Q000097:blood; D002945:Cisplatin / Q000633:toxicity; D015251:Epirubicin / Q000633:toxicity; D007668:Kidney / Q000187:drug effects*; D007674:Kidney Diseases / Q000097:blood / Q000139:chemically induced*; D008107:Liver Diseases / Q000097:blood; D008297:Male; D008727:Methotrexate / Q000633:toxicity; D009584:Nitrogen / Q000097:blood; D009588:Nitrogen Mustard Compounds / Q000633:toxicity; D011188:Potassium / Q000097:blood; D051381:Rats; D017208:Rats, Wistar; D012964:Sodium / Q000097:blood; D015431:Weight Loss / Q000187:drug effects; D005723:gamma-Glutamyltransferase / Q000097:blood
D000970:Antineoplastic Agents; D001378:Azasteroids; D001786:Blood Glucose; D009588:Nitrogen Mustard Compounds; D002699:Chlorambucil; D015251:Epirubicin; C017888:NSC 290205; D002784:Cholesterol; D012964:Sodium; D005723:gamma-Glutamyltransferase; D001219:Aspartate Aminotransferases; D000410:Alanine Transaminase; D000469:Alkaline Phosphatase; D009584:Nitrogen; D002945:Cisplatin; D011188:Potassium; D008727:Methotrexate