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

Abstract

<jats:p> 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 V<jats:sub>max</jats:sub> of the enzymes was decreased in BBM from CDDP treated rats while the K<jats:sub>m</jats:sub> remained unchanged. The Na<jats:sup>+</jats:sup>-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. </jats:p>

Effect of cisplatin on brush border membrane enzymes and anti-oxidant system of rat intestine

“…CP treatment caused maximum decrease in the activity of AP, both in the mucosal homogenates and isolated membrane vesicles. This is in contrast to renal BBM enzymes where GGTase was found to be the most affected enzyme (Fatima et al, 2004). There was a greater decrease in the activities of AP, GGTase and LAP in mucosal homogenates than in BBMV.…”

Vitamin C attenuates cisplatin-induced alterations in renal brush border membrane enzymes and phosphate transport

“…There is a significant decrease in Na ϩ -dependent Pi transport across BBMV after administration of a single dose of cisplatin. 26 We show here that the reduction in Pi transport by cisplatin is ameliorated by pretreatment with vitamin C. Administration of cisplatin alone resulted in almost 40% decrease in Pi transport while in BBMV from vitamin C pretreated animals it was only 22% less from control values. Cisplatin treatment also leads to decrease in glucose and organic cation transport across the BBM.…”

“…26 This treatment also leads to a significant reduction in the activities of several renal BBM enzymes and Na ϩ -dependent Pi transport with maximum damage observed four days after treatment. 26 All rats injected with cisplatin alone showed an increase in BUN and Scr levels indicating renal damage. In the present study we have investigated the effect of pretreatment with vitamin C on cisplatin-induced nephrotoxicity and changes in the functions of renal BBM.…”

“…We have previously shown that administration of a single dose of cisplatin to adult rats leads to a significant decrease in the activities of renal BBM enzymes and inorganic phosphate (Pi) transport. 26 The aim of the present study was to examine the effect of prior administration of vitamin C on cisplatin-induced changes in the functions of renal BBM and nephrotoxicity. Renal function was investigated by determining blood urea nitrogen (BUN) and serum creatinine (Scr) levels.…”

Protective Effect of Montelukast Which Is Cysteinyl-Leukotriene Receptor Antagonist on Gentamicin-Induced Nephrotoxicity and Oxidative Damage in Rat Kidney

“…A number of environmental variables including certain drugs influence these functions. [1][2][3] Aminoglycoside antibiotics, including gentamicin (GEN), are widely used in the treatment of gram-negative infections. A major complication of these drugs is nephrotoxicity, and it has been estimated that approximately 10-20% of the cases were treated with aminoglycoside therapy.…”