Effect of cisplatin on renal brush border membrane enzymes and phosphate transport. 2004

Sabiha Fatima, and Ahad Noor Khan Yusufi, and Riaz Mahmood
Department of Biochemistry, Faculty of Life Sciences, Aligarh Muslim University, Aligarh 202002, UP, India.

Cisplatin (CDDP) is widely used in the treatment of various cancers but its clinical use is associated with dose limiting nephrotoxicity. The present work was carried out to study the effect of administration of CDDP on rat renal brush border membrane (BBM) marker enzymes and inorganic phosphate (Pi) transport across BBM vesicles (BBMV). Animals were administered a single intraperitoneal dose of CDDP (6 mg/kg body weight) or normal saline and then sacrificed 2, 4, 8 and 16 days after this treatment. The administration of CDDP resulted in increased serum creatinine and blood urea nitrogen levels and decreased activity of BBM marker enzymes in the BBM as well as in the homogenates of cortex and medulla. Kinetic studies showed that the Vmax of the enzymes was decreased in BBM from CDDP treated rats while the Km remained unchanged. The Na+ -gradient dependent transport of Pi across BBMV was also significantly reduced after CDDP treatment. These results strongly suggest that the administration of a single nephrotoxic dose of CDDP results in impairment of the functions of renal BBM.

UI MeSH Term Description Entries
D007668 Kidney Body organ that filters blood for the secretion of URINE and that regulates ion concentrations. Kidneys
D007931 Leucyl Aminopeptidase A zinc containing enzyme of the hydrolase class that catalyzes the removal of the N-terminal amino acid from most L-peptides, particularly those with N-terminal leucine residues but not those with N-terminal lysine or arginine residues. This occurs in tissue cell cytosol, with high activity in the duodenum, liver, and kidney. The activity of this enzyme is commonly assayed using a leucine arylamide chromogenic substrate such as leucyl beta-naphthylamide. Cytosol Aminopeptidase,Leucine Aminopeptidase,L-Leucylnaphthylamidase,Methoxyleucine Aminopeptidase,Peptidase S,Zinc-Manganese-Leucine Aminopeptidase,Aminopeptidase, Cytosol,Aminopeptidase, Leucine,Aminopeptidase, Leucyl,Aminopeptidase, Methoxyleucine,Aminopeptidase, Zinc-Manganese-Leucine,Zinc Manganese Leucine Aminopeptidase
D008297 Male Males
D008871 Microvilli Minute projections of cell membranes which greatly increase the surface area of the cell. Brush Border,Striated Border,Border, Brush,Border, Striated,Borders, Brush,Borders, Striated,Brush Borders,Microvillus,Striated Borders
D010710 Phosphates Inorganic salts of phosphoric acid. Inorganic Phosphate,Phosphates, Inorganic,Inorganic Phosphates,Orthophosphate,Phosphate,Phosphate, Inorganic
D001806 Blood Urea Nitrogen The urea concentration of the blood stated in terms of nitrogen content. Serum (plasma) urea nitrogen is approximately 12% higher than blood urea nitrogen concentration because of the greater protein content of red blood cells. Increases in blood or serum urea nitrogen are referred to as azotemia and may have prerenal, renal, or postrenal causes. (From Saunders Dictionary & Encyclopedia of Laboratory Medicine and Technology, 1984) BUN,Nitrogen, Blood Urea,Urea Nitrogen, Blood
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
D005723 gamma-Glutamyltransferase An enzyme, sometimes called GGT, with a key role in the synthesis and degradation of GLUTATHIONE; (GSH, a tripeptide that protects cells from many toxins). It catalyzes the transfer of the gamma-glutamyl moiety to an acceptor amino acid. GGTP,Glutamyl Transpeptidase,gammaglutamyltransferase,gamma-Glutamyl Transpeptidase,Transpeptidase, Glutamyl,Transpeptidase, gamma-Glutamyl,gamma Glutamyl Transpeptidase,gamma Glutamyltransferase
D000469 Alkaline Phosphatase An enzyme that catalyzes the conversion of an orthophosphoric monoester and water to an alcohol and orthophosphate. EC 3.1.3.1.

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