The protection against gentamicin nephrotoxicity in the streptozotocin-induced diabetic rat is not related to gender.
Since gender can influence the renal toxicity of a drug in a given species, the present study was undertaken to evaluate the role of sex in the protection against gentamicin (G)-induced nephrotoxicity afforded by diabetes mellitus (DM) in the rat. We have compared the effects of administration of G (40 mg/kg/day, for 14 days) on male and female DM Sprague-Dawley rats. Non-diabetic animals of both sexes receiving identical doses of G served as controls. At the end of the experiment on day 14, both female (F) and male (M) control groups had similar and marked evidence of nephrotoxicity: elevation of plasma creatinine (F 1.7 +/- 0.7; M 2.8 +/- 0.6 mg/dl), decrease in endogenous 24-h creatinine clearance (Ccr) (F0.3 +/- 0.1; M 0.2 +/- 0.1 ml/min/100 g BW), and histological evidence of severe acute tubular necrosis. In marked contrast, the DM rats showed no functional or morphological evidence of renal damage throughout the study regardless of their gender (day 14: plasma creatinine: F 0.2 +/- 0.03; M 0.2 +/- 0.02; Ccr: F 1.2 +/- 0.1; M 1.6 +/- 0.1 ml/min/100 g BW), and they also accumulated less G in their kidney cortex than the C rats. The male controls exhibited higher renal cortex accumulation of G than the female controls (p < 0.05), whereas the opposite occurred in the DM groups (p < 0.01). Because the validity of using Ccr for the evaluation of GFR changes in experimental nephrotoxicity has been questioned, we have compared, in a separate experiment, three different methods of estimation of GFR (simultaneous short clearances of inulin and Ccr, and 24-h Ccr) in conscious female Sprague-Dawley rats undergoing the same treatment with G described above. At no time during the study did the method used for estimation of the GFR influence the results. We conclude that male and female Sprague-Dawley rats with diabetes are functionally and morphologically equally protected against G. Furthermore, no gender-related differences in the magnitude of G-induced nephrotoxicity was demonstrated in the non-diabetic control animals.
Gouvea
W
W
Research Medical and Pathology Service, Veterans Affairs Medical Center, Miami, Florida 33125.
Vaamonde
C M
CM
Owens
B
B
Alpert
H
H
Pardo
V
V
Vaamonde
C A
CA
D000818:Animals; D003404:Creatinine / Q000097:blood / Q000652:urine; D003921:Diabetes Mellitus, Experimental / Q000503:physiopathology*; D005260:Female; D005839:Gentamicins / Q000493:pharmacokinetics / Q000633:toxicity*; D005919:Glomerular Filtration Rate; D007668:Kidney / Q000187:drug effects* / Q000473:pathology; D007672:Kidney Cortex / Q000378:metabolism; D007684:Kidney Tubules / Q000187:drug effects; D008297:Male; D009113:Muramidase / Q000652:urine; D009336:Necrosis; D051381:Rats; D017207:Rats, Sprague-Dawley; D012727:Sex Characteristics
D005839:Gentamicins; D003404:Creatinine; D009113:Muramidase