Effects of inhibitors of the activity of cyclo-oxygenase-2 on the hypotension and multiple organ dysfunction caused by endotoxin: a comparison with dexamethasone

British Journal of Pharmacology
M LeachC Thiemermann

Abstract

1. Endotoxaemia is associated with the expression of the inducible isoform of cyclo-oxygenase, cyclo-oxygenase-2 (COX-2), and an overproduction of arachidonic acid (AA) metabolites. The role of the AA metabolites generated by COX-2 in the circulatory failure and multiple organ dysfunction caused by endotoxin is unclear. Dexamethasone prevents the expression of COX-2 and exerts beneficial effects in animal models of shock. 2. Here we compare the effects of two inhibitors of COX-2 activity, namely NS-398 (5 mg kg(-1), i.p., n=7) and SC-58635 (3 mg kg(-1), i.p., n=9) with those of dexamethasone (3 mg kg(-1), i.p., n=9) on the circulatory failure and organ dysfunction caused by lipopolysaccharide (LPS, E. coli, 6 mg kg(-1), i.v., n=11) in the rat. 3. Endotoxaemia for 6 h caused hypotension, acute renal dysfunction, hepatocellular injury, pancreatic injury and an increase in the plasma levels of 6-keto-PGF1alpha (indicator of the induction of COX-2) and nitrite/nitrate (indicator of the induction of iNOS). 4. Pretreatment of rats with dexamethasone attenuated the hypotension, the renal dysfunction, the hepatocellular and pancreatic injury and the induction of COX-2 and iNOS caused by LPS. In contrast, inhibition of COX-2 activity wi...Continue Reading

References

Mar 1, 1978·Prostaglandins·J A Salmon
Aug 1, 1992·International Journal of Immunopharmacology·M SironiP Ghezzi
Oct 1, 1990·The Journal of Clinical Investigation·J L MasferrerP Needleman
May 1, 1990·Proceedings of the National Academy of Sciences of the United States of America·R G KilbournR F Lodato
Dec 15, 1989·Biochemical and Biophysical Research Communications·C Yokoyama, T Tanabe
Jan 1, 1987·Annual Review of Pharmacology and Toxicology·G Feuerstein, J M Hallenbeck
Sep 1, 1981·The Journal of Pharmacy and Pharmacology·G FeuersteinI J Kopin
Dec 1, 1981·Proceedings of the National Academy of Sciences of the United States of America·L C GreenS R Tannenbaum
Nov 9, 1995·Biochemical Pharmacology·J A MitchellT J Williams
May 1, 1994·European Journal of Biochemistry·T KosakaT Tanabe
Dec 15, 1993·Proceedings of the National Academy of Sciences of the United States of America·J A MitchellJ R Vane
Apr 10, 1997·The New England Journal of Medicine·P J Barnes, M Karin

❮ Previous
Next ❯

Citations

Dec 4, 2003·Prostaglandins, Leukotrienes, and Essential Fatty Acids·Abed N Azab, Jacob Kaplanski
Oct 9, 2003·Kidney International·Prabal K ChatterjeeChristoph Thiemermann
Sep 25, 2001·Journal of Pediatric Gastroenterology and Nutrition·F E MartinezJ Belik
Jun 12, 2009·American Journal of Physiology. Regulatory, Integrative and Comparative Physiology·Alexandre A SteinerAndrej A Romanovsky
Jun 6, 2012·Mediators of Inflammation·David M Aronoff
May 7, 2013·Toxicology in Vitro : an International Journal Published in Association with BIBRA·Fu-Chen KuoYi-Ching Lo
Dec 27, 2016·Biomedicine & Pharmacotherapy = Biomédecine & Pharmacothérapie·Erdem Kamil OzerAlper Bektas Iskit
Jan 31, 2004·Hepatology : Official Journal of the American Association for the Study of Liver Diseases·Hiroyuki KatagiriMasataka Majima
Apr 22, 2018·The Journal of Immunology : Official Journal of the American Association of Immunologists·Erin TheisenJohn-Demian Sauer
Jun 10, 2000·Arteriosclerosis, Thrombosis, and Vascular Biology·K ZacharowskiC Thiemermann
May 6, 2011·American Journal of Physiology. Regulatory, Integrative and Comparative Physiology·Mette StæhrBoye L Jensen
Jan 10, 2001·FASEB Journal : Official Publication of the Federation of American Societies for Experimental Biology·M C McDonaldC Thiemermann
Sep 12, 2003·British Journal of Pharmacology·R d'Emmanuele di Villa BiancaR Sorrentino
Jul 22, 2018·Pflügers Archiv : European journal of physiology·Manuel MeurerKlaus Höcherl
Jan 23, 2008·The Journal of Immunology : Official Journal of the American Association of Immunologists·Takashi HamadaAna J Coito
Jan 7, 2000·Anesthesia and Analgesia·P T MurrayJ G Umans

❮ Previous
Next ❯

Related Concepts

Trending Feeds

COVID-19

Coronaviruses encompass a large family of viruses that cause the common cold as well as more serious diseases, such as the ongoing outbreak of coronavirus disease 2019 (COVID-19; formally known as 2019-nCoV). Coronaviruses can spread from animals to humans; symptoms include fever, cough, shortness of breath, and breathing difficulties; in more severe cases, infection can lead to death. This feed covers recent research on COVID-19.

Blastomycosis

Blastomycosis fungal infections spread through inhaling Blastomyces dermatitidis spores. Discover the latest research on blastomycosis fungal infections here.

Nuclear Pore Complex in ALS/FTD

Alterations in nucleocytoplasmic transport, controlled by the nuclear pore complex, may be involved in the pathomechanism underlying multiple neurodegenerative diseases including Amyotrophic Lateral Sclerosis and Frontotemporal Dementia. Here is the latest research on the nuclear pore complex in ALS and FTD.

Applications of Molecular Barcoding

The concept of molecular barcoding is that each original DNA or RNA molecule is attached to a unique sequence barcode. Sequence reads having different barcodes represent different original molecules, while sequence reads having the same barcode are results of PCR duplication from one original molecule. Discover the latest research on molecular barcoding here.

Chronic Fatigue Syndrome

Chronic fatigue syndrome is a disease characterized by unexplained disabling fatigue; the pathology of which is incompletely understood. Discover the latest research on chronic fatigue syndrome here.

Evolution of Pluripotency

Pluripotency refers to the ability of a cell to develop into three primary germ cell layers of the embryo. This feed focuses on the mechanisms that underlie the evolution of pluripotency. Here is the latest research.

Position Effect Variegation

Position Effect Variagation occurs when a gene is inactivated due to its positioning near heterochromatic regions within a chromosome. Discover the latest research on Position Effect Variagation here.

STING Receptor Agonists

Stimulator of IFN genes (STING) are a group of transmembrane proteins that are involved in the induction of type I interferon that is important in the innate immune response. The stimulation of STING has been an active area of research in the treatment of cancer and infectious diseases. Here is the latest research on STING receptor agonists.

Microbicide

Microbicides are products that can be applied to vaginal or rectal mucosal surfaces with the goal of preventing, or at least significantly reducing, the transmission of sexually transmitted infections. Here is the latest research on microbicides.