Inhibition of COX-1 attenuates the formation of thromboxane A2 and ameliorates the acute decrease in glomerular filtration rate in endotoxemic mice

Mederle K, Meurer M, Castrop H, Höcherl K (2015)

Publication Type: Journal article

Publication year: 2015

Journal

American Journal of Physiology-Renal Physiology American Physiological Society

Book Volume: 309

Pages Range: F332-40

Journal Issue: 4

DOI: 10.1152/ajprenal.00567.2014

Abstract

Thromboxane (Tx) A2 has been suggested to be involved in the development of sepsis-induced acute kidney injury (AKI). Therefore, we investigated the impact of cyclooxygenase (COX)-1 and COX-2 activity on lipopolysaccharide (LPS)-induced renal TxA2 formation, and on endotoxemia-induced AKI in mice. Injection of LPS (3 mg/kg ip) decreased glomerular filtration rate (GFR) and the amount of thrombocytes to ~50% of basal values after 4 h. Plasma and renocortical tissue levels of TxB2 were increased ~10- and 1.7-fold in response to LPS, respectively. The COX-1 inhibitor SC-560 attenuated the LPS-induced fall in GFR and in platelet count to ~75% of basal levels. Furthermore, SC-560 abolished the increase in plasma and renocortical tissue levels of TxB2 in response to LPS. The COX-2 inhibitor SC-236 further enhanced the LPS-induced decrease in GFR to ~40% of basal values. SC-236 did not alter thrombocyte levels nor the LPS-induced increase in plasma and renocortical tissue levels of TxB2. Pretreatment with clopidogrel inhibited the LPS-induced drop in thrombocyte count, but did not attenuate the LPS-induced decrease in GFR and the increase in plasma TxB2 levels. This study demonstrates that endotoxemia-induced TxA2 formation depends on the activity of COX-1. Our study further indicates that the COX-1 inhibitor SC-560 has a protective effect on the decrease in renal function in response to endotoxin. Therefore, our data support a role for TxA2 in the development of AKI in response to LPS.

Authors with CRIS profile

Manuel Meurer Lehrstuhl für Pharmakologie und Toxikologie Klaus Höcherl Professur für Molekulare Pharmakologie

Involved external institutions

Universität Regensburg DE Germany (DE)

How to cite

APA:

Mederle, K., Meurer, M., Castrop, H., & Höcherl, K. (2015). Inhibition of COX-1 attenuates the formation of thromboxane A2 and ameliorates the acute decrease in glomerular filtration rate in endotoxemic mice. American Journal of Physiology-Renal Physiology, 309(4), F332-40. https://doi.org/10.1152/ajprenal.00567.2014

MLA:

Mederle, Katharina, et al. "Inhibition of COX-1 attenuates the formation of thromboxane A2 and ameliorates the acute decrease in glomerular filtration rate in endotoxemic mice." American Journal of Physiology-Renal Physiology 309.4 (2015): F332-40.

BibTeX: Download