Omega-3 polyunsaturated fatty acids as an angelus custos to rescue patients from NSAID-induced gastroduodenal damage

Abstract

Nonsteroidal anti-inflammat ory drugs (NSAIDs) are one of the drug types frequently prescribed for their analgesic, anti-inflammatory, and antithrombotic actions, but carry a risk of major gastroduodenal damage from mild erosive changes to serious ulceration leading to fatal outcomes. From the long history of willow tree bark and its extracts being applied for the relief of pain and fever, the synthesis of acetylsalicylic acid, the development of selective cyclooxygenase 2 inhibitors (coxibs), and the identification of a G-protein-coupled receptor for prostaglandin, the popular combination regimen of an NSAID and a proton pump inhibitor was invented, but development was continued for further improvement. With regard to major NSAID adverse effects, gastrointestinal (GI) and cardiovascular (CV) risks still remained as problems to be solved. In this review, it is shown that n-3 polyunsaturated fatty acid (PUFA) based NSAIDs can be an angelus custos, supported with facts that an intake of essential n-3 PUFAs orchestrates concerted protective actions against two notorious side effects of NSAIDs, the aforementioned GI risk and CV risk of NSAIDs. Since pills containing n-3 PUFAs, omega-3-acid ethyl ester capsules (Lovaza, Omarcor), have already been safely prescribed to prevent atherosclerosis through lessening lipid burdening, the introduction of a drug delivery system such as a gastroretentive form of n-3 PUFA based NSAIDs will highlight newer hope for GI safety under the guarantee of reduced CV risk. Because n-3 PUFAs have been proven to attenuate cytotoxicity, inhibit lipid-raft-associated harmful signaling, and relieve oxidative stress relevant to NSAIDs, n-3 PUFA based NSAIDs will be next-generation GI-safe NSAIDs.

Mitigation of indomethacin-induced gastrointestinal damages in fat-1 transgenic mice via gate-keeper action of ω-3-polyunsaturated fatty acids

“…In order to improve GI safety, NO-releasing NSAID, H 2 S-releasing NSAIDs, and PC-conjugated NSAIDs are under active investigation or clinical trials 16 17 18 33 . However, NSAID-induced GI damage goes beyond authentic COX inhibition, including changes to the hydrophobicity, fluidity, biomechanics, and permeability of extracellular and membrane phospholipids 6 .…”

Natural remedies for non‐steroidal anti‐inflammatory drug‐induced toxicity

“…Trefoil peptide was stated to cure the gastrotoxicity caused by indomethacin (Levenstein et al, 2015). Complications related to gastrotoxicity are often relatively high due to the excessive use of coffee, alcohol and NSAIDs (Park et al, 2015). The formation of gastrotoxicity can be minimized by using the lowest effective dose of NSAIDs and for short periods (Ilic et al, 2011).…”

“…Few studies have reported problems of NSAIDs in cardiac muscle, which ultimately leads to heart failure. Ulcers and gastrointestinal lesions have been diagnosed in 40% of people who have used NSAIDs on a regular basis (Park et al, 2015). Usage of NSAIDs against Helicobacter pylori infection was reported to have caused severe peptic ulcer in a study by Huang et al (2002).…”

Effects of Omega-3 Co-Administered with Therapeutic Dose of lornoxicam on Male Rats' Liver

“…Omega-3 poly-unsaturated fatty-acid (PUFAs) including docosahexaenoic acid (DHA) and eicosapentaenoic acid (EPA) is an essential oil for the development of fetal and health aging; it plays a role in anti-inflammatory process and cell membrane viscosity (6,7) . Furthermore, it has been reported that the intake of omega-3 PUFA may provide a protective impact against the most common adverse effects of NSAIDs such as cardiovascular and gastrointestinal (8) . The drugliver interaction and drug-drug interaction must also be considered.…”