In utero and in vitro exposure to beta-lactams impair kidney development in the rat.
beta-Lactam antibiotics are widely used because of their lack of toxicity in humans. However, during pregnancy, exposure of the fetus is likely to occur because beta-lactam antibiotics cross the placenta. The potential adverse effects of two penicillins (ampicillin, amoxicillin) and of one cephalosporin (ceftriaxone) were examined in rat kidney development. Two experimental approaches were used: metanephros organ cultures to analyze the direct effect of the drug and maternal treatment to assess the consequences of in utero exposure. For in vitro experiments, metanephroi were removed from 14-d-old fetuses and grown with or without the antibiotic at a concentration ranging from 10 to 1000 microg/ml for 6 d. For in vivo experiments, pregnant rats were treated with penicillin at 100 mg/kg per d for 5 d, a period overlapping early renal organogenesis. Both penicillins alter renal development in vitro in a dose-dependent manner, from a dose of 10 microg/ml for ampicillin and 100 microg/ml for amoxicillin. In young animals exposed to penicillins in utero, a mild oligonephronia was present and cystic tubule dilation was observed in newborn and in young animals as well. Ceftriaxone weakly impairs in vitro nephrogenesis except at the dose of 1000 microg/ml that blocks kidney development completely. No effect on nephron ontogeny was observed following in utero exposure, but an interstitial inflammation was present in the medulla of 2-wk-old rats. In conclusion, these data show that beta-lactams, at therapeutic doses, are harmful to fetal rat kidneys.
Nathanson
Sylvie
S
Institut National de la Santé et de la Recherche Médicale U319, Université Paris 7-Denis Diderot, France.
Moreau
Evelyne
E
Institut National de la Santé et de la Recherche Médicale U319, Université Paris 7-Denis Diderot, France.
Merlet-Benichou
Claudie
C
Institut National de la Santé et de la Recherche Médicale U319, Université Paris 7-Denis Diderot, France.
Gilbert
Thierry
T
Institut National de la Santé et de la Recherche Médicale U319, Université Paris 7-Denis Diderot, France.
D000658:Amoxicillin / Q000633:toxicity; D000667:Ampicillin / Q000633:toxicity; D000704:Analysis of Variance; D000818:Animals; D000900:Anti-Bacterial Agents / Q000633:toxicity*; D002443:Ceftriaxone / Q000633:toxicity; D002511:Cephalosporins / Q000633:toxicity; D016009:Chi-Square Distribution; D005260:Female; D005333:Fetus / Q000187:drug effects*; D007668:Kidney / Q000187:drug effects* / Q000196:embryology; D010406:Penicillins / Q000633:toxicity; D011247:Pregnancy; D011256:Pregnancy Outcome; D011297:Prenatal Exposure Delayed Effects; D051381:Rats; D017207:Rats, Sprague-Dawley; D018709:Statistics, Nonparametric
D000900:Anti-Bacterial Agents; D002511:Cephalosporins; D010406:Penicillins; D002443:Ceftriaxone; D000667:Ampicillin; D000658:Amoxicillin