NSAIDs and Cardiovascular Diseases: Role of Reactive Oxygen Species

Abstract

Nonsteroidal anti-inflammatory drugs (NSAIDs) are the most commonly used drugs worldwide. NSAIDs are used for a variety of conditions including pain, rheumatoid arthritis, and musculoskeletal disorders. The beneficial effects of NSAIDs in reducing or relieving pain are well established, and other benefits such as reducing inflammation and anticancer effects are also documented. The undesirable side effects of NSAIDs include ulcers, internal bleeding, kidney failure, and increased risk of heart attack and stroke. Some of these side effects may be due to the oxidative stress induced by NSAIDs in different tissues. NSAIDs have been shown to induce reactive oxygen species (ROS) in different cell types including cardiac and cardiovascular related cells. Increases in ROS result in increased levels of oxidized proteins which alters key intracellular signaling pathways. One of these key pathways is apoptosis which causes cell death when significantly activated. This review discusses the relationship between NSAIDs and cardiovascular diseases (CVD) and the role of NSAID-induced ROS in CVD.

Non-steroidal Anti-inflammatory Drugs Are Caspase Inhibitors

“…Unlike previously identified NSAID targets observed only at high doses (mM), caspase inhibition occurs at micromolar concentrations in biological systems, consistent with physiological levels of NSAIDs (5–500 μM), and comparable to the IC 50 values for COX (Ghosh et al, 2015; Gierse et al, 1999; Kato et al, 2001; Piazza et al, 1997). While inhibition is not comparable to that of potent, irreversible pan-caspase inhibitors such as z-VAD-FMK, at physiological concentrations caspase inhibition by NSAIDs may still have unforeseen effects on patients.…”

“…Reported NSAID functions include inhibition of NF-κB, inhibition of proteasome function, activation of intrinsic and extrinsic pathways of apoptosis, cell cycle arrest, and activation of stress kinases (Jana, 2008; Leibowitz et al, 2014). However, many of these effects are seen only at superphysiological concentrations, limiting their biological relevance (Ghosh et al, 2015; Mehlisch and Sykes, 2013). Here, we have identified cysteine-aspartic proteases (caspases) as novel targets for some NSAIDs such as ibuprofen, naproxen, and ketorolac at physiologic concentrations.…”

Will peripherally restricted kappa-opioid receptor agonists (pKORAs) relieve pain with less opioid adverse effects and abuse potential?

“…Opioids are the more effective for treating severe pain. NSAID‐induced analgesic activity results from the inhibition of cyclooxygenase (COX) isozymes (COX‐1 and COX‐2), but unfortunately their use is associated with the occurrence of serious adverse effects (e.g., gastrointestinal bleeding, platelet function alteration, and cardiovascular system and organ damage) . Although the mechanism of action of acetaminophen‐induced analgesic activity is not fully understood, it likely involves actions on the central nervous system (and an interaction between brain and spinal cord) .…”

A narrative review of non-operative treatment, especially traditional Chinese medicine therapy, for lumbar intervertebral disc herniation

“…NSAIDs are the most widely used over-the-counter drugs as well as the most prescribed class of drugs for a variety of conditions including pains, rheumatoid arthritis, osteoarthritis, musculoskeletal disorders, and other comorbid conditions (68). Millions of people suffer from pain resulting in the prolonged use of NSAIDs being common.…”