K. Hamilton et al., EFFECT OF EXPERIMENTAL DIABETES-MELLITUS ON GENTAMICIN-INDUCED ACUTE RENAL FUNCTIONAL-CHANGES IN THE ANESTHETIZED RAT, Clinical and experimental pharmacology and physiology, 25(3-4), 1998, pp. 231-235
1. Rats with streptozotocin (STZ) diabetes are protected from gentamic
in (GEN) nephrotoxicity, Because the chronic renal damage from GEN is
preceded by acute renal functional changes (notably hypercalciuria), t
he present study aims to determine whether diabetes may also protect a
gainst the acute effects of the drug, If there is a link between the r
apid physiological actions of GEN and its subsequent nephrotoxicity, t
he former may also be affected by the diabetic condition, 2. Standard
renal clearance techniques were performed on anaesthetized rats that h
ad been injected with STZ or vehicle 2 weeks previously, All animals w
ere infused with 0.9% NaCl for 5 h and then either GEN (0.28 mg/kg per
min) or 0.9 % NaCl alone for 2 h, 3. Baseline fractional calcium excr
etion (FECa) of diabetic rats was three-fold that of control animals (
6.6+/-0.2 vs 2.2+-0.2%, respectively; P<0.01, MANOVA), Following GEN i
nfusion, a comparable increase in FECa occurred in control and diabeti
c rats (5.3+/-0.6 vs 5.3+/-0.8%, respectively; NS), 4. Streptozotocin
diabetes, therefore, does not alter the acute hypercalciuric response
to GEN, This may suggest that the acute effects of GEN on renal calciu
m handling do not contribute to the subsequent nephrotoxicity. However
, the higher baseline FECa seen in diabetic rats may afford protection
against the renal injury caused by gentamicin.