Prenatal exposure to high level of glucocorticoids increases the susceptibility of renal proximal tubular cells to apoptosis induced by uropathogenic Escherichia coli toxins.
Prenatal exposure to excessive glucocorticoids may alter the developing fetus inducing metabolic and endocrine imbalance in various organs, including the kidney. This study aimed at evaluating whether prenatal exposure to high levels of glucocorticoids adversely affects renal cell survival and predisposes to renal cell death. Pregnant rats were injected with 0.1 mg/kg dexamethasone (DEX) i.p. from day 1 of gestation. Renal proximal tubular cells (PTCs) were prepared from 20-day-old offspring in the DEX (DEX cells) and control groups (CON cells). After 4 days' culture, cells were exposed to uropathogenic Escherichia coli ARD6 toxins at concentrations known to induce apoptotic cell death. We found that cell death rate was significantly higher in DEX than in CON cells. Cells exhibited morphological and biochemical features of apoptosis. Conversely, the activity of the antioxidant enzyme catalase was significantly increased in renal cortex homogenate from 20-day-old DEX rats. The antioxidant vitamin E did not prevent apoptosis. These results indicate that prenatal exposure to high levels of glucocorticoids induces alterations in renal PTCs rendering them more sensitive to E. coli toxins via nonoxidative stress. With the increasing use of multiple doses of glucocorticoids in preterm infants, the possibility that antenatal glucocorticoids may lead to renal adverse consequences is of clinical relevance.
Chen
Ming
M
Pediatric Nephrology Unit, Karolinska University Hospital-Huddinge, Karolinska Institutet, Stockholm, Sweden. Ming.Chen@klinvet.ki.se
Bao
Wenjie
W
Ceccatelli
Sandra
S
Celsi
Gianni
G
D000818:Animals; D017209:Apoptosis / Q000187:drug effects; D001427:Bacterial Toxins / Q000009:adverse effects*; D016923:Cell Death / Q000187:drug effects; D004926:Escherichia coli; D005260:Female; D005938:Glucocorticoids / Q000008:administration & dosage / Q000009:adverse effects*; D007687:Kidney Tubules, Proximal / Q000187:drug effects* / Q000473:pathology*; D011247:Pregnancy; D011297:Prenatal Exposure Delayed Effects; D051381:Rats; D017207:Rats, Sprague-Dawley
D001427:Bacterial Toxins; D005938:Glucocorticoids