TY - JOUR
T1 - Impact of Early Postnatal NSAID Treatment on Nephrogenesis in Wistar Rats
AU - Bueters, Ruud R. G.
AU - Klaasen, Annelies
AU - Maicas, Nuria
AU - Florquin, Sandrine
AU - van den Heuvel, Lambertus P.
AU - Schreuder, Michiel F.
PY - 2015
Y1 - 2015
N2 - BACKGROUND: Prematurely born children with patent ductus arteriosus are treated with ibuprofen or indomethacin, which may inhibit kidney development. We determined whether clinical doses affected kidney development and function, with or without extrauterine growth retardation. METHODS: Wistar rats were cross-fostered in normal food (NF) or food restricted (FR) litters at postnatal day (PND) 2. On PND 3 to 4, three doses of 0.9% NaCl, 0.1 mg/kg indomethacin, or 10 mg/kg ibuprofen were administered via intraperitoneal injection with 12-hr intervals. Kidneys were evaluated for apoptosis, proliferation, and gene expression at PND 8; stereological assessment of nephron number at PND 35; and clinical pathology and neutrophil gelatinase-associated lipocalin at 4 and 9 months. Blood pressure was measured at the ages of 4, 6, and 9 months. RESULTS: NF and FR bodyweight differed from PND 3 onwards, ranging from 16.5 g at weaning (p <0.001) to 39 g at necropsy (p = 0.019). Kidney proliferation/apoptosis ratios were 7:1 and 3:1 (p = 0.001), respectively and different expression of Wnt4 (0.7x), Oat1 (1.3x), Nphs1 (1.7x), and Aqp4 (1.3x) was noted (but its biological relevance doubted). Nephron numbers were decreased by 12% (p = 0.109) in the ibuprofen-NF group and 7.5% (p = 0.237) in FR groups. This coincided with a tendency to increased neutrophil gelatinase-associated lipocalin at 9 months. No differences were noted in electrolytes, creatinine, or urea clearance. No valid blood pressure results could be obtained. CONCLUSION: A clinical Ibuprofen dose showed potential to inhibit kidney development in neonatal rats. FR did not modulate these effects
AB - BACKGROUND: Prematurely born children with patent ductus arteriosus are treated with ibuprofen or indomethacin, which may inhibit kidney development. We determined whether clinical doses affected kidney development and function, with or without extrauterine growth retardation. METHODS: Wistar rats were cross-fostered in normal food (NF) or food restricted (FR) litters at postnatal day (PND) 2. On PND 3 to 4, three doses of 0.9% NaCl, 0.1 mg/kg indomethacin, or 10 mg/kg ibuprofen were administered via intraperitoneal injection with 12-hr intervals. Kidneys were evaluated for apoptosis, proliferation, and gene expression at PND 8; stereological assessment of nephron number at PND 35; and clinical pathology and neutrophil gelatinase-associated lipocalin at 4 and 9 months. Blood pressure was measured at the ages of 4, 6, and 9 months. RESULTS: NF and FR bodyweight differed from PND 3 onwards, ranging from 16.5 g at weaning (p <0.001) to 39 g at necropsy (p = 0.019). Kidney proliferation/apoptosis ratios were 7:1 and 3:1 (p = 0.001), respectively and different expression of Wnt4 (0.7x), Oat1 (1.3x), Nphs1 (1.7x), and Aqp4 (1.3x) was noted (but its biological relevance doubted). Nephron numbers were decreased by 12% (p = 0.109) in the ibuprofen-NF group and 7.5% (p = 0.237) in FR groups. This coincided with a tendency to increased neutrophil gelatinase-associated lipocalin at 9 months. No differences were noted in electrolytes, creatinine, or urea clearance. No valid blood pressure results could be obtained. CONCLUSION: A clinical Ibuprofen dose showed potential to inhibit kidney development in neonatal rats. FR did not modulate these effects
U2 - https://doi.org/10.1002/bdrb.21161
DO - https://doi.org/10.1002/bdrb.21161
M3 - Article
C2 - 26375421
SN - 1542-9733
VL - 104
SP - 218
EP - 226
JO - Birth defects research. Part B, Developmental and reproductive toxicology
JF - Birth defects research. Part B, Developmental and reproductive toxicology
IS - 5
ER -