Abstract
Sepsis causes severe dysregulation of organ functions, via the development of oxidative stress and inflammation. These pathophysiological mechanisms are mimicked in mice injected with bacterial lipopolysaccharide (LPS). Here, protective properties of argan oil against LPS-induced oxidative stress and inflammation are explored in the murine model. Mice received standard chow, supplemented with argan oil (AO) or olive oil (OO) for 25 days, before septic shock was provoked with a single intraperitoneal injection of LPS, 16 hours prior to animal sacrifice. In addition to a rise in oxidative stress and inflammatory markers, injected LPS also caused hepatotoxicity, accompanied by hyperglycemia, hypercholesterolemia and hyperuremia. These LPS-associated toxic effects were blunted by AO pretreatment, as corroborated by normal plasma parameters and cell stress markers (glutathione: GSH) and antioxidant enzymology (catalase, CAT; superoxide dismutase, SOD and glutathione peroxidase, GPx). Hematoxylin–eosin staining revealed that AO can protect against acute liver injury, maintaining a normal status, which is pointed out by absent or reduced LPS-induced hepatic damage markers (i.e., alanine aminotransferase (ALT) and aspartate transaminase (AST)). Our work also indicated that AO displayed anti-inflammatory activity, due to down-regulations of genes encoding pro-inflammatory cytokines Interleukin-6 (IL-6) and Tumor Necrosis Factor-α (TNF-α) and in up-regulations of the expression of anti-inflammatory genes encoding Interleukin-4 (IL-4) and Interleukin-10 (IL-10). OO provided animals with similar, though less extensive, protective changes. Collectively our work adds compelling evidence to the protective mechanisms of AO against LPS-induced liver injury and hence therapeutic potentialities, in regard to the management of human sepsis. Activations of IL-4/Peroxisome Proliferator-Activated Receptors (IL-4/PPARs) signaling and, under LPS, an anti-inflammatory IL-10/Liver X Receptor (IL-10/LXR) route, obviously indicated the high potency and plasticity of the anti-inflammatory properties of argan oil.
Highlights
Sepsis is characterized by severe organ dysfunctions, requiring intensive care, and is associated with a high mortality rate [1,2]
The host develops an acute syndrome under exposure to endotoxins, which are released from bacteria membranes and trigger a potent inflammatory cytokine response, leading to severe impairment of lipid metabolism [3,4,5]
In the two groups treated with either argan oil (AO) or olive oil (OO) alone, no significant modifications were shown for most measured plasmatic parameters
Summary
Sepsis is characterized by severe organ dysfunctions, requiring intensive care, and is associated with a high mortality rate [1,2]. Metabolic changes are mainly accounted for by increased hepatic triglyceride synthesis and adipocyte lipolysis, which is associated with a reduced level of fatty acid oxidation (FAOx) in several tissues, including heart, kidney, liver and skeletal muscle [4,14,15,16,17]. OO has been suggested as a suitable fat, which may be recommended in clinical nutrition [21] In this context, the present study was aimed at a more in-depth investigation of the antioxidant and anti-inflammatory properties of argan oil, compared to olive oil, in livers from mice exposed to LPS. Pro- and anti- inflammatory gene expressions were concomitantly determined, in order to get a relatively integrated view and decisive breakthrough in our understanding of the molecular basis of AO-driven counteraction of liver sepsis
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