Inhibition of COX-1 attenuates the formation of thromboxane A2and ameliorates the acute decrease in glomerular filtration rate in endotoxemic mice
| Autor: | Hayo Castrop, Katharina Mederle, Klaus Höcherl, Manuel Meurer |
|---|---|
| Rok vydání: | 2015 |
| Předmět: |
Blood Platelets
Male medicine.medical_specialty Time Factors Physiology Thromboxane Down-Regulation Renal function Inflammation Kidney Thromboxane A2 chemistry.chemical_compound Internal medicine medicine Animals Platelet Cyclooxygenase 2 Inhibitors biology Acute kidney injury Membrane Proteins Acute Kidney Injury medicine.disease Endotoxemia Endotoxins Mice Inbred C57BL Disease Models Animal Endocrinology chemistry Decreased glomerular filtration rate Immunology Cyclooxygenase 1 biology.protein Pyrazoles Cyclooxygenase medicine.symptom Platelet Aggregation Inhibitors Glomerular Filtration Rate Signal Transduction |
| Zdroj: | American Journal of Physiology-Renal Physiology. 309:F332-F340 |
| ISSN: | 1522-1466 1931-857X |
| DOI: | 10.1152/ajprenal.00567.2014 |
| Popis: | Thromboxane (Tx) A2has 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 TxA2formation, 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 TxB2were 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 TxB2in 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 TxB2levels. This study demonstrates that endotoxemia-induced TxA2formation 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 TxA2in the development of AKI in response to LPS. |
| Databáze: | OpenAIRE |
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