Adverse effects caused by Non-steroidal anti-inflammatory drugs(NSAIDS) are due to dysfunctional molecular and cellular mechanisms.

‘Carprofen could trigger low-grade inflammation in heart and kidneys and this risk increases if the patient had a heart attack.’
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Ganesh Halade, Ph.D., associate professor in the UAB Department of Medicine’s Division of Cardiovascular Disease, wanted to see if carprofen affected either of the two steps the immune system takes to repair heart attack damage. Read More..





First is an immediate acute inflammation, where leukocytes rush into heart muscle to remove dead cells and cell debris. Second is the subsequent resolution phase to dampen the excess inflammation caused by those activated leukocytes, which otherwise would further damage the heart and kidneys.
In a study published in the journal Life Sciences, Halade and colleagues found that carprofen treatment alone triggered subtle low-grade inflammation in the heart and kidneys. The combination of carprofen pretreatment and heart attack magnified this impact by dysregulating the acute inflammatory response, amplifying inflammation and intensifying the cardiorenal syndrome.
Specifically, the UAB researchers first found that carprofen without heart attack triggered kidney inflammation, as measured by increased levels of plasma creatinine, NGAL and KIM-1, all biomarkers of kidney injury. They also found inflamed proximal convoluted tubules and compromised glomerular structure integrity in the kidneys.
Second, they found that carprofen without heart attack caused increased levels of the inflammatory cytokines TNF-alpha and IL-1 beta, and increased levels of the enzyme COX-2, which normally is induced at the start of the inflammation process after injury to produce chemoattractants that recruit immune cells.
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Third, when the pretreatment with carprofen was followed by heart attack, the proinflammatory cytokines TNF-alpha and IL-1-beta decreased, rather than increasing as they do in response to heart attacks without carprofen pretreatment.
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This KIM-1 dysfunction led to less clearance of dead cells from the heart. Also, carprofen pretreatment and heart attack amplified subsequent kidney tissue damage, as compared with kidney damage after heart attack alone.
Source-Eurekalert