Pharmacological evaluation of the effects of enzymatically liberated fish oil on eosinophilic inflammation in animal models

Abstract

The inappropriate activation of eosinophils is a well-recognized driver of various human inflammatory diseases including asthma, chronic rhinitis, and various gastrointestinal diseases, including eosinophilic esophagitis. Steroids, both topical and systemic, remain a cornerstone of treatment and can be highly effective.However, some individuals suffer side effects, unresolved symptoms, or both. OmeGo, an enzymatically liberated fish oil, has demonstrated anti-inflammatory and antioxidant properties as well the reduction of the activation, migration, and survival of eosinophils. Two animal models of eosinophilic inflammation were used to further assess OmeGo's profile. A house dust mite model of induced asthma showed a significant reduction in eosinophilic lung inflammation compared to the negative control, linoleic acid. The CRTH2 antagonist fevipiprant showed a similar eosinophilic inhibitory profile to OmeGo. In contrast, cod liver oil had no impact on any measure of inflammation. A guinea pig model of mild intraperitoneal eosinophilia showed a significant reduction in eosinophil activity by OmeGo, assessed by chemotaxis and chemokinesis. Apolipoprotein A-IV, an endogenous human protein with anti-inflammatory actions, showed a similar but numerically lower effect. OmeGo therefore combines a consistent antieosinophilic action with the known anti-inflammatory effects of polyunsaturated fatty acids. Proof-of-concept studies in asthma are warranted.

Assessing the Anti-Inflammatory Effects of an Orally Dosed Enzymatically Liberated Fish Oil in a House Dust Model of Allergic Asthma

“…In this study, oral OmeGo significantly reduced lung and splenic eosinophilia compared to cod liver oil (vehicle control) in a house dust mite (HDM) mouse model of asthma. These results are consistent with previous work that assessed OmeGo’s modulation of eosinophil function, including in vivo studies with OmeGo dosed via intraperitoneal injection [ 12 ] and in vitro work in human eosinophils [ 13 ].…”

“…This contrasting effect between OmeGo and cod liver oil is consistent with our previous work on the modulation of eosinophil function with OmeGo. This effect appears to be driven by a bioactive fraction not present in highly processed supplements [ 12 , 13 ]. The variable outcomes seen with omega-3 supplementation compared to the consumption of fresh fish [ 10 ] suggests that minimal processing helps to retain the full bioactivity of the individual PUFAs to provide health benefits associated with eating fresh fish.…”

“…The number of animals selected was guided by our previous HDM work, in which OmeGo was dosed intraperitoneally (IP) in five animals per group [ 12 ] and showed a significant 42% reduction in serum eosinophil count. To be conservative, in case of greater inter-animal responses with oral OmeGo compared to IP dosing, we chose to double the size to 10 animals per group in the present study.…”

“…OmeGo is minimally processed whole fish oil with low levels of oxidation and free fatty acids and contains all of the polyunsaturated acids found in whole fish, not just omega-3. Previous in vitro work demonstrated OmeGo to significantly reduce eosinophilic effector function, whereas this was not the case for oils containing either omega-3 alone or omega-3 and astaxanthin [ 12 ], and a similar comparative profile between OmeGo and omega-3 oils was also demonstrated in animal models of induced eosinophilia [ 13 ]. As these previous in vivo studies administered OmeGo by the intraperitoneal route, this paper describes experiments focused now on oral delivery, to provide information that is more relevant to its use in humans.…”

Role of Cathepsin K Inhibitor & Atorvastatin in Protection Against Atherosclerosis in High Fat Diet-Fed Rats

“…OmeGo is an enzymatically liberated salmon oil which contains all 21 omegas and fatty acids present in the oil fraction of whole fish. Our previous work has shown OmeGo to have antioxidant and anti-inflammatory properties enabling the reduction in oxidised LDL in healthy human subjects and the attenuation of allergic inflammation in preclinical models [15][16][17][18].…”