Acute gentamicin‐induced hypercalciuria and hypermagnesiuria in the rat: dose‐response relationship and role of renal tubular injury

Abstract

1 Standard renal clearance techniques were used to assess the dose-response relationship between acute gentamicin infusion and the magnitude of hypercalciuria and hypermagnesiuria in the anaesthetized Sprague-Dawley rat. Also investigated were whether these e ects occurred independently of renal tubular cell injury. 2 Acute gentamicin infusion was associated with a signi®cant hypercalciuria and hypermagnesiuria evident within 30 min of drug infusion. The magnitude of these responses was related to the dose of drug infused (0.14 ± 1.12 mg kg 71 min 71 ). Increased urinary electrolyte losses resulted from a decreased tubular reabsorption of calcium and magnesium. 3 A rapid dose-related increase in urinary N-acetyl-b-D-glucosaminidase (NAG) excretion was also observed in response to gentamicin infusion. However, there was no evidence of renal tubular cell injury and no myeloid bodies were observed within the lysosomes of the proximal tubular cells. Gentamicin may thus interfere with the mechanisms for cellular uptake and intracellular processing of NAG causing increased NAG release into the tubular lumen. 4 The absence of changes in renal cellular morphology indicates that the excessive renal losses of calcium and magnesium were an e ect of gentamicin per se and not the result of underlying renal tubular injury. The renal e ects described in this paper were apparent after administration of relatively low total drug doses, and with plasma concentrations calculated to be within the clinical range. These ®ndings suggest that disturbances of plasma electrolyte homeostasis could occur in the absence of overt renal injury in patients receiving aminoglycoside antibiotics.

Effects of Ashwagandha (Withania somnifera) Root Extract Against Gentamicin Induced Changes of Serum Electrolytes in Rats

“…This finding is in agreement with that of some other researchers 3,16,18 . Again, some other researchers observed significantly lower level of serum sodium ion in gentamicin treated group after ashwagandha treatment in comparison to that of baseline control group 15 .…”

“…Abnormal electrolytes concentrations reflect altered metabolic status 3 . Electrolyte imbalance can leads to serious consequences as it affects the homeostasis of the body.…”

Aminoglycosides Increase Intracellular Calcium Levels and ERK Activity in Proximal Tubular OK Cells Expressing the Extracellular Calcium-Sensing Receptor

“…Previous studies have indicated drug accumulation in the cytosol of renal cortical cells as the main cause for AGA nephrotoxicity (1,2). However, the time necessary for AGA uptake and sequestration into the lysosomal compartment, rupture and release of the lysosomal content exceeds that described for early markers of cytotoxicity (6,10). Although it is not disputed that a megalin/ cubilin complex might represent the endocytic receptor for polybasic drugs (7), our study indicates that AGAs rapidly stimulate signal transduction pathways common to many Gqcoupled receptors.…”

“…In addition, several drugs such as antihistamines and tetracyclines accumulate into the cytosol of proximal tubular cells, causing myeloid body formation, but significant clinical or experimental nephrotoxicity is rare (9). In addition to the cellular damage and the accompanying fall in GFR, acute gentamicin treatment in rat results in significant hypercalciuria and hypermagnesuria and a rapid dose-related increase in urinary N-acetyl-␤-D-glucosaminidase (a brush border marker for early gentamicin toxicity) well before tubular injury and histologic changes take place (10). Moreover, dietary calcium loading reduces the nephrotoxic potential of the drug, but it does not reduce drug accumulation in the renal cortex (11).…”

Effects of furosemide on renal calcium handling

“…To verify the effects of furosemide-induced hypercalciuria on DCT calcium transport molecules, we added a gentamicin-treated group (n ϭ 8 mice) as a hypercalciuric control because gentamicin can induce hypercalciuria without renal tubular damages (25). The mice were administered with a single subcutaneous dose of gentamicin (40 mg/kg) daily for 4 days.…”