Anti-inflammatory, Carprofen, Cytokines, Non-resolving inflammation, Renal inflammation
Digital Object Identifier (DOI)
Non-Steroidal Anti-Inflammatory Drugs (NSAIDs) are commonly used to control pain, inflammation, and limit the cardinal signs of injury in humans. However, prolonged use of NSAIDs increases the risk of heart attack (myocardial infarction; MI) and the subsequent risk of heart and renal failure. The molecular and cellular mechanism of action for this adverse effect, particularly along the cardiorenal network, is incomplete. To define the mechanism, carprofen (CAP), an NSAID was administered at the dose of 5 mg/kg to C57BL/6 male mice for two weeks. After last dose of CAP treatment mice were subjected to permanent occlusion of coronary artery that induces irreversible cardiac remodeling while maintaining naive and MI-controls. After MI, cardiac pathology and dysfunction were confirmed, along with additional measurements of kidney function, histology, and injury markers, such as plasma creatinine. CAP treatment increased plasma creatinine levels and subsequently, myocardial structural disorganization increased. Kidney neutrophil gelatinase associated lipocalin (NGAL) and protein expression were increased post-MI. After two weeks CAP treatment, the expression of pyrogenic pro-inflammatory cytokines TNF-α and IL-1β was increased compared to non-CAP treated mice, indicative of amplified inflammatory response. There was also evidence that renal injury of both the post-CAP treatment controls and post-CAP MI were much greater than the non-CAP treated naïve controls, as serum creatinine and NGAL levels were elevated along with obvious structural impairment of the glomerulus. Therefore, CAP treatment tampers with the acute inflammatory response that promotes cardiorenal syndrome and non-resolving inflammation post-MI in acute heart failure.
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Citation / Publisher Attribution
Life Sciences, v. 218, p. 224-232
This article is the post-print author version. Final version available at: https://doi.org/10.1016/j.lfs.2018.12.048
Scholar Commons Citation
Krishnan, Veena; Booker, David; Cunningham, Gabrielle; Jadapalli, Jeevan Kumar; Kain, Vasundhara; Pullen, Amanda B.; and Halade, Ganesh V., "Pretreatment of Carprofen Impaired Initiation of Inflammatory- and Overlapping Resolution Response and Promoted Cardiorenal Syndrome in Heart Failure" (2019). Internal Medicine Faculty Publications. 14.