Silva 2016 Thesis

Silva Luana Caroline Schüeler da (2016) Fucoxantina inibe a oxidação de LDL e ativação de macrófagos in vitro. PhD Thesis:93 pp.

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Silva Luana Caroline Schueler da (2016) Dissertation

Abstract: Nowadays, cardiovascular diseases are the leading cause of mortality and morbitidy worldwide. In turn, atherosclerosis, mainly cause of cardiovascular diseases, is an inflammatory and chronic pathology characterized by the accumulation of lipids and cellular elements in the intima layer of arteries of medium and large caliber. Abnormal production of reactive species related to several risk factors for this pathology, and consequently the oxidative modification of low density lipoprotein (LDL) play an important role in the pathogenesis of this condition. One possible method to prevent atherosclerotic diseases would be the administration of antioxidant substances thereby making LDL less sensitive to this oxidative process, preventing or delaying the disease progression. For this reason, the inclusion of dietary antioxidants represents a concrete alternative in controlling the progression of atherogenesis. Fucoxanthin, a carotenoid extracted from edible brown seaweed, has excellent anti-inflamatory and antioxidative activities already demonstrated in several experimental models. In this context, the objective of this study was to investigate the potential antioxidant and antiatherogenic effects of the compound fucoxanthin on the inhibition of human isolated LDL oxidation, as well on macrophages J774 expose to oxidized LDL (oxLDL). Initially, we evaluated the protective effects of fucoxanthin on human Cu²⁺-induced human LDL oxidation. The compound caused a concentration-dependent inhibition on the LDL lipoperoxidation. Furthermore, the protein moieties oxidation from human isolated LDL was also inhibited in a concentration-dependent manner. Considering the antioxidative protective effects of fucoxanthin, and considering the involvement of oxLDL in the pathogenesis of atherosclerosis, we investigated the protective effects of fucoxanthin on oxLDL-mediated cytotoxic effects in murine macrophage cells. The 24 hours pre-treatment with fucoxanthin reduced the cytotoxic effects caused by oxLDL, including elevated production of reactive oxygen and nitrogen species (ROS/RNS), disturbance of .NO homeostasis, reduction of intracellular levels of reduced glutathione (GSH), foam cell formation and impairment in mitochondrial bioenergetics. The potential antiatherogenic effect of fucoxanthin was related to its ability of scavenging free radicals, as well as activating transcription factors as Nrf-2, and inhibit the activity of NF-ϰB, as reported in the literature. The results indicate a beneficial role of fucoxanthin in atherogenesis by preventing oxidative events that may contribute to disease progression. • Keywords: Atherosclerosis, Low density lipoprotein, Macrophages, Carotenoids • Bioblast editor: Kandolf G • O2k-Network Lab: BR Florianopolis De Bem AF

Labels: MiParea: Respiration, Exercise physiology;nutrition;life style, Pharmacology;toxicology  Pathology: Cardiovascular  Stress:Oxidative stress;RONS  Organism: Human 

Preparation: Intact cells 

Coupling state: LEAK, ROUTINE, ET  Pathway: ROX  HRR: Oxygraph-2k