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Acetylsalicylic acid interferes with embryonic kidney growth and development by a prostaglandin-independent mechanism

Welham, Simon J.M.; Sparrow, Alexander J.; Gardner, David S.; Elmes, Matthew J.

Authors

Alexander J. Sparrow

Matthew J. Elmes



Abstract

AIM: To evaluate the effects of the non-selective, non-steroidal anti-inflammatory drug (NSAID) acetylsalicylic acid (ASA), on ex vivo embryonic kidney growth and development.
METHODS: Pairs of fetal mouse kidneys at embryonic day 12.5 were cultured ex vivo in increasing concentrations of ASA (0.04-0.4 mg/mL) for up to 7 d. One organ from each pair was grown in control media and was used as the internal control for the experimental contralateral organ. In some experiments, organs were treated with ASA for 48 h and then transferred either to control media alone or control media containing 10 μmol/L prostaglandin E2 (PGE2) for a further 5 d. Fetal kidneys were additionally obtained from prostaglandin synthase 2 homozygous null or heterozygous (PTGS2-/- and PTGS2-/+) embryos and grown in culture. Kidney cross-sectional area was used to determine treatment effects on kidney growth. Whole-mount labelling to fluorescently detect laminin enabled crude determination of epithelial branching using confocal microscopy.
RESULTS: Increasing ASA concentration (0.1, 0.2 and 0.4 mg/mL) significantly inhibited metanephric growth (P < 0.05). After 7 d of culture, exposure to 0.2 mg/mL and 0.4 mg/mL reduced organ size to 53% and 23% of control organ size respectively (P < 0.01). Addition of 10 μmol/L PGE2 to culture media after exposure to 0.2 mg/mL ASA for 48 h resulted in a return of growth area to control levels. Application of control media alone after cessation of ASA exposure showed no benefit on kidney growth. Despite the apparent recovery of growth area with 10 μmol/L PGE2, no obvious renal tubular structures were formed. The number of epithelial tips generated after 48 h exposure to ASA was reduced by 40% (0.2 mg/mL; P < 0.05) and 47% (0.4 mg/mL; P < 0.01). Finally, growth of PTGS2-/- and PTGS2+/- kidneys in organ culture showed no differences, indicating that PTGS2 derived PGE2 may at best have a minor role.
CONCLUSION: ASA reduces early renal growth and development but the role of prostaglandins in this may be minor.

Citation

Welham, S. J., Sparrow, A. J., Gardner, D. S., & Elmes, M. J. (2017). Acetylsalicylic acid interferes with embryonic kidney growth and development by a prostaglandin-independent mechanism. World Journal of Nephrology, 6(1), https://doi.org/10.5527/WJN.v6.i1.21

Journal Article Type Article
Acceptance Date Oct 22, 2016
Publication Date Jan 6, 2017
Deposit Date Jan 11, 2017
Publicly Available Date Jan 11, 2017
Journal World Journal of Nephrology
Electronic ISSN 2220-6124
Publisher Baishideng Publishing Group
Peer Reviewed Peer Reviewed
Volume 6
Issue 1
DOI https://doi.org/10.5527/WJN.v6.i1.21
Keywords Acetylsalicylic acid; Nephrogenesis; Kidney culture; Non-steroidal anti-inflammatory drug; Prostaglandins;
Prostaglandin synthase 2
Public URL http://eprints.nottingham.ac.uk/id/eprint/39734
Publisher URL http://www.wjgnet.com/2220-6124/full/v6/i1/21.htm
Copyright Statement Copyright information regarding this work can be found at the following address: http://creativecommons.org/licenses/by-nc/4.0

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Copyright Statement
Copyright information regarding this work can be found at the following address: http://creativecommons.org/licenses/by-nc/4.0





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