Antibiotic therapy reduces nitrosative stress and programmed cell death in the rabbit foetal lung.
The correlation of clinical and epidemiological data suggests that intrauterine infection/inflammation can promote foetal lung injury. The aim of this study was: 1) to characterise the early inflammatory response elicited in infected foetal lungs, in terms of nitric oxide-derived oxidative stress and programmed cell death; and 2) to investigate the effects of antibiotic therapy on these parameters. A previously described rabbit experimental model of materno-foetal infection was used. Animals were divided into three groups: controls; Escherichia coli infected (12 h); and E. Coli infected (12 h) and treated (24 h gentamicin+ceftriaxone). Foetal lungs were examined in terms of histology, nitric oxide synthase (NOS) activity, immunohistochemical detection of 3-nitrotyrosine, and detection of apoptotic cells by the TUNEL assay and Hoechst staining. In the infected group, a moderate inflammatory response was observed, associated with a significant increase in inducible NOS activity, the formation of 3-nitrotyrosine residues in epithelial and immune cells, the down-regulation of constitutive NOS activity and clusters of apoptotic cells, as compared with the control group. Early antibiotic therapy, initiated at 12 h post-inoculation, elicited a significant decrease in the infection-induced nitrosative stress. Levels of 3-nitrotyrosine and of apoptotic cells were decreased in the infected-and-treated group compared with the infected group, mainly by the re-expression of constitutive NOS and of the basal level of inducible NOS. Altogether, these findings indicate that early antibiotic therapy can curb the inflammatory reaction and help avert antenatal lung injury, which is known to be involved in the onset of bronchopulmonary dysplasia.
Gras-Le Guen
C
C
Laboratoire d'Antibiologie Clinique et Expérimentale, Faculté de Médecine, 1 rue G Veil, 44035 Nantes, France. christele.grasleguen@chu-nantes.fr
Jarry
A
A
Vallette
G
G
Toquet
C
C
Colombeix
C
C
Laboisse
C L
CL
Potel
G
G
Roze
J-C
JC
Bugnon
D
D
Debillon
T
T
D000704:Analysis of Variance; D000818:Animals; D000900:Anti-Bacterial Agents / Q000494:pharmacology*; D017209:Apoptosis / Q000187:drug effects / Q000502:physiology; D004195:Disease Models, Animal; D005260:Female; D005333:Fetus / Q000187:drug effects / Q000473:pathology; D007150:Immunohistochemistry; D020287:In Situ Nick-End Labeling; D008168:Lung / Q000187:drug effects / Q000473:pathology; D019001:Nitric Oxide Synthase / Q000187:drug effects / Q000378:metabolism*; D018384:Oxidative Stress / Q000187:drug effects / Q000502:physiology*; D018410:Pneumonia, Bacterial / Q000188:drug therapy* / Q000473:pathology; D011247:Pregnancy; D011251:Pregnancy Complications, Infectious; D011270:Pregnancy, Animal; D011336:Probability; D011817:Rabbits; D012016:Reference Values; D012680:Sensitivity and Specificity
D000900:Anti-Bacterial Agents; D019001:Nitric Oxide Synthase