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In utero and in vitro exposure to beta-lactams impair kidney development in the rat
Sylvie Nathanson1, Evelyne Moreau1, Claudie Merlet-Benichou1
1Institut National de la Santé et de la Recherche Médicale U319, Université Paris 7-Denis Diderot, France.
Insights
Beta-lactam antibiotics, commonly used medications, can harm developing fetal rat kidneys. Studies show adverse effects on kidney development from both in vitro and in utero exposure to penicillins and cephalosporins.
Area of Science:
- Pharmacology
- Developmental Biology
- Toxicology
Background:
- Beta-lactam antibiotics are frequently prescribed due to their low human toxicity.
- These antibiotics can cross the placenta, leading to potential fetal exposure during pregnancy.
Purpose of the Study:
- To investigate the adverse effects of specific beta-lactam antibiotics on fetal rat kidney development.
- To compare the impact of in vitro exposure versus in utero exposure on renal organogenesis.
Main Methods:
- Metanephros organ cultures were used to assess direct drug effects in vitro.
- Pregnant rats were treated with antibiotics to evaluate consequences of in utero exposure.
- Antibiotic concentrations ranged from 10 to 1000 microg/ml in vitro, and in vivo doses were 100 mg/kg/day.
Main Results:
- Both ampicillin and amoxicillin impaired in vitro renal development in a dose-dependent manner.
- In utero penicillin exposure resulted in oligonephronia and cystic tubule dilation in offspring.
- Ceftriaxone inhibited in vitro nephrogenesis at high doses and caused interstitial inflammation in vivo.
Conclusions:
- Beta-lactam antibiotics, even at therapeutic doses, can be detrimental to fetal kidney development in rats.
- The findings highlight potential risks associated with beta-lactam use during pregnancy.
Abstract:
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.