Mederle, Katharina and Meurer, Manuel and Castrop, Hayo and Hoecherl, Klaus (2015) Inhibition of COX-1 attenuates the formation of thromboxane A(2) and ameliorates the acute decrease in glomerular filtration rate in endotoxemic mice. AMERICAN JOURNAL OF PHYSIOLOGY-RENAL PHYSIOLOGY, 309 (4). F332-F340. ISSN 1931-857X, 1522-1466
Full text not available from this repository. (Request a copy)Abstract
Thromboxane (Tx) A(2) 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 TxA(2) 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 similar to 50% of basal values after 4 h. Plasma and renocortical tissue levels of TxB(2) were increased similar to 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 similar to 75% of basal levels. Furthermore, SC-560 abolished the increase in plasma and renocortical tissue levels of TxB(2) in response to LPS. The COX-2 inhibitor SC-236 further enhanced the LPS-induced decrease in GFR to similar to 40% of basal values. SC-236 did not alter thrombocyte levels nor the LPS-induced increase in plasma and renocortical tissue levels of TxB(2). 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 TxB(2) levels. This study demonstrates that endotoxemia-induced TxA(2) 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 TxA(2) in the development of AKI in response to LPS.
| Item Type: | Article |
|---|---|
| Uncontrolled Keywords: | ACUTE-RENAL-FAILURE; LIPOPOLYSACCHARIDE-INDUCED THROMBOCYTOPENIA; ACUTE KIDNEY INJURY; PLATELET-AGGREGATION; IN-VIVO; CYCLOOXYGENASE-2 INHIBITION; CARDIOVASCULAR FAILURE; CONSCIOUS MICE; SEVERE SEPSIS; SEPTIC SHOCK; lipopolysaccharide; cyclooxygenase; acute kidney injury; thromboxane; inflammation |
| Subjects: | 600 Technology > 610 Medical sciences Medicine |
| Divisions: | Biology, Preclinical Medicine > Institut für Physiologie > Prof. Dr. Wolf Hayo Castrop |
| Depositing User: | Dr. Gernot Deinzer |
| Date Deposited: | 14 Jun 2019 11:00 |
| Last Modified: | 14 Jun 2019 11:00 |
| URI: | https://pred.uni-regensburg.de/id/eprint/5015 |
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