Changes in serum, liver and kidneys of cisplatin-treated rats; effects of antioxidants.
Cisplatin, a nephrotoxic chemotherapeutic agent, was injected into Sprague Dawley rats, alone or together with cysteine, vitamin E and clonidine. The effects on erythrocyte fragility, serum composition, and kidney and liver enzymes were studied. Cisplatin was administered as two i.p. injections (6 mg/kg body weight) at an interval of 120 hours. The animals were sacrificed 24 hours after the second injection. Erythrocytes were prepared from blood collection with anticoagulant. Serum was prepared from clotted blood, collected without anticoagulant. Kidneys and liver were removed and homogenized, and a supernatant prepared by high speed centrifugation. In cisplatin-treated rats, the serum activities of aspartate aminotransferase, alanine aminotransferase, lactic dehydrogenase and alkaline phosphatase were significantly decreased, whereas the activities of isocitric dehydrogenase and glutathione reductase were increased. Also, concentrations of blood urea nitrogen, creatinine, total lipids and magnesium increased while albumin and glucose decreased. Mean osmotic fragility of erythrocytes from cisplatin-treated rats was decreased, while the haematocrit was increased. In the liver, the only change seen was an increased activity of isocitric dehydrogenase. Much greater changes were found in the kidneys, with increased activity of glucose-6-phosphate dehydrogenase and decreased activities of aspartate and alanine aminotransferases, alkaline phosphatase, malic dehydrogenase, sorbitol dehydrogenase and gamma-glutamyltransferase, as well as a decreased phosphorylation to oxidation ratio in the mitochondria, indicating reduced adenosine triphosphate production. Administration of cysteine and vitamin E together with cisplatin partially reversed the uraemia and many of the biochemical changes induced by cisplatin.(ABSTRACT TRUNCATED AT 250 WORDS)
Bogin
E
E
Dept. of Biochemistry, Kimron Veterinary Institute, Beit-Dagan, Israel.
Marom
M
M
Levi
Y
Y
D000818:Animals; D000975:Antioxidants / Q000494:pharmacology*; D001798:Blood Proteins / Q000378:metabolism; D002945:Cisplatin / Q000037:antagonists & inhibitors / Q000097:blood* / Q000494:pharmacology*; D003000:Clonidine / Q000494:pharmacology; D003545:Cysteine / Q000494:pharmacology; D004347:Drug Interactions; D004912:Erythrocytes / Q000187:drug effects* / Q000201:enzymology; D005980:Glutathione Reductase / Q000187:drug effects / Q000378:metabolism; D007521:Isocitrate Dehydrogenase / Q000187:drug effects / Q000378:metabolism; D007668:Kidney / Q000187:drug effects* / Q000201:enzymology; D007674:Kidney Diseases / Q000139:chemically induced; D008099:Liver / Q000187:drug effects* / Q000201:enzymology; D008297:Male; D008928:Mitochondria / Q000187:drug effects / Q000378:metabolism; D010084:Oxidation-Reduction; D010766:Phosphorylation; D051381:Rats; D017207:Rats, Sprague-Dawley; D014810:Vitamin E / Q000494:pharmacology
D000975:Antioxidants; D001798:Blood Proteins; D014810:Vitamin E; D007521:Isocitrate Dehydrogenase; D005980:Glutathione Reductase; D003545:Cysteine; D003000:Clonidine; D002945:Cisplatin