title: Phlorizin-induced glycosuria does not prevent gentamicin nephrotoxicity in rats.
abstract: 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 groups 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 CCr 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 CCr at day 9.89%, P less than 0.001; peak lysozymuria, 1863 +/- 321 micrograms/day; and tubular necrosis score, 3.9 +/- 0.1). These values were not different from those of Group III: maximal decrease in CCr 73% (P less than 0.001); lysozymuria, 2147 +/- 701 micrograms/day; tubular necrosis score, 3.8 +/- 0.1.(ABSTRACT TRUNCATED AT 250 WORDS)
authors.affiliation: Medical Service, Veterans Administration Medical Center, Miami, Florida.
authors.forename: W L
authors.initials: WL
authors.lastname: Gouvea
authors.forename: H C
authors.initials: HC
authors.lastname: Alpert
authors.forename: J
authors.initials: J
authors.lastname: Kelley
authors.forename: V
authors.initials: V
authors.lastname: Pardo
authors.forename: C A
authors.initials: CA
authors.lastname: Vaamonde
mesh_terms: D058186:Acute Kidney Injury / Q000139:chemically induced / Q000517:prevention & control; D000818:Animals; D003921:Diabetes Mellitus, Experimental / Q000097:blood / Q000150:complications / Q000503:physiopathology; D005260:Female; D005839:Gentamicins / Q000378:metabolism / Q000633:toxicity*; D006029:Glycosuria / Q000097:blood / Q000139:chemically induced / Q000503:physiopathology*; D007668:Kidney / Q000473:pathology / Q000503:physiopathology; D007672:Kidney Cortex / Q000378:metabolism; D010695:Phlorhizin; D051381:Rats; D011919:Rats, Inbred Strains
chemical_list: D005839:Gentamicins; D010695:Phlorhizin