Interspecies Differences in Renal Localization of Cyclooxygenase Isoforms: Implications in Nonsteroidal Antiinflammatory Drug-Related Nephrotoxicity

Autor: Jacquline A. Brassard, Timothy J. Maziasz, Carl L. Alden, Benjamin E. Trump, Catherine M. Venturini, Roderick T. Bunch, Kanwar Nasir M. Khan, Alane T. Koki, Dale L. Morris
Rok vydání: 1998
Předmět:
Adult
medicine.medical_specialty
040301 veterinary sciences
In situ hybridization
Pharmacology
Kidney
Toxicology
030226 pharmacology & pharmacy
Isozyme
Pathology and Forensic Medicine
Nephrotoxicity
Rats
Sprague-Dawley
0403 veterinary science
03 medical and health sciences
Basal (phylogenetics)
Dogs
0302 clinical medicine
Species Specificity
Internal medicine
medicine
Animals
Humans
Cyclooxygenase Inhibitors
RNA
Messenger
Molecular Biology
In Situ Hybridization
Cyclooxygenase 2 Inhibitors
biology
Anti-Inflammatory Agents
Non-Steroidal
Membrane Proteins
04 agricultural and veterinary sciences
Cell Biology
Middle Aged
Immunohistochemistry
Rats
Isoenzymes
Macaca fascicularis
medicine.anatomical_structure
Endocrinology
Mechanism of action
Cyclooxygenase 2
Prostaglandin-Endoperoxide Synthases
Toxicity
Cyclooxygenase 1
biology.protein
Kidney Diseases
Cyclooxygenase
medicine.symptom
Zdroj: Toxicologic Pathology. 26:612-620
ISSN: 1533-1601
0192-6233
DOI: 10.1177/019262339802600504
Popis: Cyclooxygenase (COX) exists in 2 related but unique isoforms: one is constitutive (COX-1) and functions in normal cell physiology, and the other is inducible (COX-2) and is expressed in response to inflammatory stimuli. Nonsteroidal antiinflammatory drugs (NSAIDs) cause renal toxicity following inhibition of renal cyclooxygenases. Humans and animals exhibit differences in susceptibility to NSAID-related renal toxicity, which may be associated with differences in expression of 1 or both isoforms of COX in the kidney. In this study, we evaluated COX-1 and COX-2 expression in the kidneys of mixed-breed dogs, Sprague-Dawley rats, cynomolgus monkeys, and humans. In addition, the effect of volume depletion on renal COX expression was investigated in rats, dogs, and monkeys. COX expression was evaluated using 1 or more of the following procedures: reverse transcriptase polymerase chain reaction, in situ hybridization, and immunohistochemistry. We demonstrated that both COX isoforms are expressed in the kidneys of all species examined, with differences in the localization and level of basal expression. COX-1 is expressed at high levels in the collecting ducts and renal vasculature of all species and in a small number of papillary interstitial cells in rats, monkeys, and humans. Basal levels of COX-2 are present in the maculae densa, thick ascending limbs, and papillary interstitial cells in rats and dogs and in glomerular podocytes and small blood vessels in monkeys and humans. COX-2 expression is markedly increased in volume-depleted rats and dogs but not monkeys. These results indicate that significant interspecies differences exist in the presence and distribution of COX isoforms, which may help explain the difference in species susceptibility to NSAID-related renal toxicity.
Databáze: OpenAIRE
Externí odkaz: