TY - JOUR
T1 - Phlorizin-induced glycosuria does not prevent gentamicin nephrotoxicity in rats
AU - Gouvea, W. L.
AU - Alpert, H. C.
AU - Kelley, J.
AU - Pardo, V.
AU - Vaamonde, C. A.
N1 - Funding Information:
American Society of Nephrology, 1981 [Kidney tnt 21:217, 19821. Dr. Gouvea, whose current address is Rio de Janeiro, Brazil 20251, was a fellow of the University of Miami School of Medicine (Renal Division). The streptozotocin was a gift from Dr. W.E. Dulin, Upjohn Laborato- ries, Kalamazoo, Michigan, USA. We thank L. Cason and G.R. Rodriguez for their invaluable technical help, and Esther Márquez for her secretarial skills. This work was supported by designated research funds (8943-008) from the Veterans Administration and by the Kidney Foundation of South Florida.
Copyright:
Copyright 2017 Elsevier B.V., All rights reserved.
PY - 1989
Y1 - 1989
N2 - Because rats with streptozotocin-induced diabetes mellitus (DM) have a high solute diuresis (glycosuria of 10 to 12 g/day), we have suggested that this may in part be responsible for their resistance to gentamicin-induced acute renal failure (ARF). The protection from gentamicin nephrotoxicity was studied in non-diabetic rats with chronic solute diuresis induced by blockage of tubular glucose reabsorption with phlorizin (P). DM rats with mild glycosuria (similar in degree to that of the P treated animals) were also studied. Unanesthetized adult female, Sprague-Dawley rats were divided in four groups and studied for 15 days. Group 1 (P alone) received P, 360 mg/day, for 15 days; Group II (P + gentamicin); Group III (gentamicin alone) and Group IV (mild DM + gentamicin). Nephrotoxic doses (40 mg/kg body wt/day) of gentamicin were injected during the last nine days of study to the animals of group II to IV. In Group I, P induced a moderate and stable glycosuria (3.9 ± 0.1 g/day, SE), and no functional or morphologic evidence of renal dysfunction (baseline C(Cr) 2.1 ± 0.1 ml/min, undetectable lysozymuria) or damage (tubular necrosis score [maximum 4], zero). In Group II, P did not prevent gentamicin-ARF (maximal decrease in C(Cr) at day 9, 89%, P < 0.001; peak lysozymuria, 1863 ± 321 μg/day; and tubular necrosis score, 3.9 ± 0.1). These values were not different from those of Group III: maximal decrease in C(Cr) 73% (P < 0.001); lysozymuria, 2147 ± 701 μg/day; tubular necrosis score, 3.8 ± 0.1. In marked contrast, Group IV DM rats with mild glycosuria (4.1 ± 1.0 g/day) were protected from gentamicin toxicity: maximal decrease in C(Cr) was 10% (from 2.0 ± 0.1 to 1.8 ± 0.1 ml/min; P < 0.001 vs. Groups II and III); peak lysozymuria, 31 ± 31 μg/day (P < 0.001 vs. Groups II and III); tubular necrosis score, 0.8 ± 0.4 (P < 0.001 vs. Groups II and III). No differences in renal cortical gentamicin accumulation were found between Groups II, III and IV (360 ± 20, 395 ± 25 and 493 ± 55 μg/g wet tissue, respectively). The later finding most likely resulted from an underestimation of gentamicin tissue levels in Groups II and III due to tubular necrosis. We conclude that P alone does not result in renal dysfunction or damage. The protection against gentamicin-ARF of DM rats with mild glycosuria, and the lack of protection in the P + G treated rats were independent of the glycosuria, solute diuresis and urine flow rate. Thus, the resistance afforded by the diabetic state to gentamicin-ARF is not explained by the enhanced solute diuresis or altered glucose transport.
AB - Because rats with streptozotocin-induced diabetes mellitus (DM) have a high solute diuresis (glycosuria of 10 to 12 g/day), we have suggested that this may in part be responsible for their resistance to gentamicin-induced acute renal failure (ARF). The protection from gentamicin nephrotoxicity was studied in non-diabetic rats with chronic solute diuresis induced by blockage of tubular glucose reabsorption with phlorizin (P). DM rats with mild glycosuria (similar in degree to that of the P treated animals) were also studied. Unanesthetized adult female, Sprague-Dawley rats were divided in four groups and studied for 15 days. Group 1 (P alone) received P, 360 mg/day, for 15 days; Group II (P + gentamicin); Group III (gentamicin alone) and Group IV (mild DM + gentamicin). Nephrotoxic doses (40 mg/kg body wt/day) of gentamicin were injected during the last nine days of study to the animals of group II to IV. In Group I, P induced a moderate and stable glycosuria (3.9 ± 0.1 g/day, SE), and no functional or morphologic evidence of renal dysfunction (baseline C(Cr) 2.1 ± 0.1 ml/min, undetectable lysozymuria) or damage (tubular necrosis score [maximum 4], zero). In Group II, P did not prevent gentamicin-ARF (maximal decrease in C(Cr) at day 9, 89%, P < 0.001; peak lysozymuria, 1863 ± 321 μg/day; and tubular necrosis score, 3.9 ± 0.1). These values were not different from those of Group III: maximal decrease in C(Cr) 73% (P < 0.001); lysozymuria, 2147 ± 701 μg/day; tubular necrosis score, 3.8 ± 0.1. In marked contrast, Group IV DM rats with mild glycosuria (4.1 ± 1.0 g/day) were protected from gentamicin toxicity: maximal decrease in C(Cr) was 10% (from 2.0 ± 0.1 to 1.8 ± 0.1 ml/min; P < 0.001 vs. Groups II and III); peak lysozymuria, 31 ± 31 μg/day (P < 0.001 vs. Groups II and III); tubular necrosis score, 0.8 ± 0.4 (P < 0.001 vs. Groups II and III). No differences in renal cortical gentamicin accumulation were found between Groups II, III and IV (360 ± 20, 395 ± 25 and 493 ± 55 μg/g wet tissue, respectively). The later finding most likely resulted from an underestimation of gentamicin tissue levels in Groups II and III due to tubular necrosis. We conclude that P alone does not result in renal dysfunction or damage. The protection against gentamicin-ARF of DM rats with mild glycosuria, and the lack of protection in the P + G treated rats were independent of the glycosuria, solute diuresis and urine flow rate. Thus, the resistance afforded by the diabetic state to gentamicin-ARF is not explained by the enhanced solute diuresis or altered glucose transport.
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U2 - 10.1038/ki.1989.88
DO - 10.1038/ki.1989.88
M3 - Article
C2 - 2709684
AN - SCOPUS:0024593589
VL - 35
SP - 1041
EP - 1048
JO - Kidney International
JF - Kidney International
SN - 0085-2538
IS - 4
ER -