A Nutraceutical Rich in Docosahexaenoic Acid Improves Portal Hypertension in a Preclinical Model of Advanced Chronic Liver Disease

Abstract

Inflammation and oxidative stress play a key role in the pathophysiology of advanced chronic liver disease (ACLD) and portal hypertension (PH). Considering the current lack of effective treatments, we evaluated an anti-inflammatory and antioxidant nutraceutical rich in docosahexaenoic acid (DHA) as a possible therapy for ACLD. We investigated the effects of two-week DHA supplementation (500 mg/kg) on hepatic fatty acids, PH, oxidative stress, inflammation, and hepatic stellate cell (HSC) phenotype in rats with ACLD. Additionally, the effects of DHA were evaluated in murine macrophages and human HSC. In contrast to vehicle-treated animals, cirrhotic rats receiving DHA reestablished a healthy hepatic fatty acid profile, which was associated with an improvement in PH. The mechanisms underlying this hemodynamic improvement included a reduction in oxidative stress and inflammation, as well as a marked HSC deactivation, confirmed in human HSC. Experiments with cultured macrophages showed that treatment with DHA protects against pro-inflammatory insults. The present preclinical study demonstrates that a nutraceutical rich in DHA significantly improves PH in chronic liver disease mainly by suppressing inflammation and oxidative stress-driven HSC activation, encouraging its evaluation as a new treatment for PH and cirrhosis.

Self-Reported Omega-3 Supplement Use Moderates the Association between Age and Exercising Cerebral Blood Flow Velocity in Older Adults

“…Additionally, a meta-analysis of randomized controlled trials found omega-3 supplementation decreased arterial stiffness in adults [35]. Finally, omega-3 fatty acids have anti-inflammatory and anti-oxidant properties [36][37][38], both of which could contribute to improved cerebrovascular health and higher blood flow during exercise in the older adults in the present study who reported taking supplements.…”

Oxidative Stress in Chronic Liver Disease and Portal Hypertension: Potential of DHA as Nutraceutical

“…In a previous publication from our research group [82], we found that ACLD's pathophysiology involves a profound deregulation of the hepatic fatty acid profile. The analysis, performed in livers from healthy and cirrhotic rats, showed that, among other alterations, cirrhotic livers are markedly depleted in DHA.…”

“…As in many other diseases, oxidative stress plays a key role in the pathogenesis of ACLD, contributing to the deregulation of all hepatic cell types and the progression of fibrosis. Indeed, the use of TG-DHA for the treatment of experimental ACLD has shown promising results [82]. However, given the complexity of the disease, the therapeutic approach for ACLD has recently shifted from monotherapy to combination therapy.…”

Pan-PPAR agonist lanifibranor improves portal hypertension and hepatic fibrosis in experimental advanced chronic liver disease

“…TAA was previously dissolved in saline solution at a concentration of 125 mg/ml and administered intraperitoneally at a dose of 250 mg/kg body weight. 21,22 Following the last TAA administration, animals with ACLD underwent a detoxification period of 2 to 5 days before beginning pharmacological treatment.…”