Effect of fetal exposure to gentamicin on kidneys of young guinea pigs

Abstract

Clearance experiments were performed with young pups born of guinea pigs given a daily injection of 4 mg of gentamicin per kg (body weight) from days 48 to 54 of gestation (term, 68 days). For 3-day-old animals, the glomerular filtration rate was similar to that measured in control guinea pigs of the same age whose mothers were given saline during the same period of gestation. The same applied to fractional excretion of water, urea, total solutes, Na, K, Ca, and Mg but not to fractional phosphate excretion, which increased significantly in the gentamicin group when compared with the controls (mean ± standard error, 21.7 ± 4.9 versus 7.3 ± 1.8%; P < 0.05; n = 6 for both). The glomerular volume of the juxtamedullary nephrons diminished by about 40%, and their proximal tubule length decreased by about 20%. The glomerular volume of the superficial nephrons also diminished, by about 30%, but their proximal tubule length did not change. The gentamicin concentration was higher in the renal cortex than in the medulla (13.1 ± 2.6 versus 5.7 ± 2.2 ,ug/g [dry wt]; P < 0.01; n = 6 for each). It decreased significantly from days 3 to 20 in both tissues. No functional impairment of the kidney was found in 10-day-old animals, and normal or even supranormal morphometry of the nephrons was observed in the 20-day-old animals. It is concluded that fetal exposure to gentamicin impairs proximal tubular function in the developing animal and might also adversely affect glomerular and tubular growth. However, both the functional and morphometric impairments of nephrons are transitory.

Antibiotics and renal branching morphogenesis: comparison of toxicities

“…The main difference between our approaches can be found in animal species (rat vs. mice in the current study) and in developmental stage. We believe the species difference is probably of secondary importance to the Articles developmental stage as effects of in utero gentamicin exposure on renal development were reported in rats, mice and guinea pigs alike (3)(4)(5)(6)(7)18). Although some differences in susceptibility may be present.…”

Indomethacin, ibuprofen and gentamicin administered during late stages of glomerulogenesis do not reduce glomerular number at 14 days of age in the neonatal rat

“…However, this in vitro finding has not been confirmed in in vivo studies of the rat or guinea pig. This may be due to the timing of doses during glomerulogenesis [11,12].…”

Delayed Developmental Effects Following Prenatal Exposure to Drugs

“…The gentamicin concentration was higher in the renal cortex than in the medulla; it decreased significantly from PD 3 to 20 in both tissues. The morphometric impairments of nephrons were transitory, as no effects were observed on PD20 [32]; however, one should not overlook the Besides in vivo studies, cultured explants of rat metanephroi may be a valuable system for investigating normal and abnormal renal organogenesis, as the model maintains the in vivo patterns of mesenchymal-epithelial interactions. The branching capacity of the ureteric bud and that of the mesenchyme to form nephrons can both be measured [26].…”