LASSBio-1425, an analog of thalidomide, decreases triglyceride and increases HDL cholesterol levels by inhibition of TNF-α production

Fumian, Milla Machado; Motta, Nadia Alice Vieira; Maia, Rodolfo do Couto; Fraga, Carlos A.M.; Barreiro, Eliezer J.; Brito, Fernanda

doi:10.1016/j.ijcard.2015.09.071

Cited by 9 publications

(17 citation statements)

References 9 publications

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“…In the present work, hyperlipidemia was induced by a 45‐day hypercholesterolemic diet in Wistar rats. Animals fed with HC diet (HC and HC + Perio) had higher levels of TC, TG, cLDL, and cVLDL and lower levels of cHDL compared with animals fed with standard diet (C) (Table ), as previously shown by our group . In contrast, we now show that periodontal disease did not increase lipid levels by itself, independently of type of diet, since there were no significant differences between Perio and respective diet groups (C vs Perio; HC vs HC + Perio).…”

Section: Discussionmentioning

confidence: 92%

“…In the current study, animals fed with HC diet also showed increased platelet aggregation in response to ADP and collagen, reproducing previous results of our group . In fact, hypercholesterolemia is described as a risk factor for atherothrombotic events also due to its capacity to induce megakaryopoiesis and increase the total platelet count (trombocytosis) .…”

Section: Discussionmentioning

confidence: 99%

“…Locally producing excess NO in damaged cells, the increased iNOS expression contributes with oxidative stress and triggers the cascade of events leading to increased vascular reaction to α 1 agonists and decreased relaxation response to acetylcholine . Indeed, in the HC group the response to the α 1 vasoconstrictor phenylephrine was increased and maximal relaxation to acetylcholine was decreased as compared to C group, reproducing previous results of our group . Periodontitis also increased the vascular response to phenylephrine; however, those results were not statistically significant.…”

Section: Discussionmentioning

confidence: 99%

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Periodontal status, vascular reactivity, and platelet aggregation changes in rats submitted to hypercholesterolemic diet and periodontitis

Silva

Motta

Soares

et al. 2020

J of Periodontal Research

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Background and objectives: Periodontitis can corroborate with development and progression of atherosclerosis and a possible bidirectional interaction between both pathologies has been hypothesized. The aim of this work was to study the interactions between diet-induced hypercholesterolemia and ligature-induced periodontitis in Wistar rats submitted to both conditions. Material and methods: Animals were divided into four experimental groups: C (control: standard diet without periodontitis), Perio (periodontitis plus standard diet), HC (high cholesterol diet without periodontitis), and HC + Perio (high cholesterol diet plus periodontitis). The diets were offered for 45 days and a silk ligature was applied in the lower first molars of Perio and HC-Perio animals on day 34 and maintained for 11 days until euthanasia. The mandibles were excised, and alveolar bone loss was determined by macroscopic and micro-tomographic (µ-CT) imaging. Blood samples were obtained, and platelet aggregation was induced in plasma rich in platelets by adenosine diphosphate (ADP) and collagen. Endothelium-dependent vascular reactivity and protein expression of endothelial (eNOS), phosphorylated endothelial (peNOS), and inducible (iNOS) nitric oxide synthases were evaluated in aorta samples. Results:The HC diet combined with periodontitis (HC + Perio group) was associated with an increased alveolar bone loss, when compared to the other groups. Both in Perio and HC groups, platelet aggregation induced by ADP or collagen was increased, while maximum aortic relaxation induced by acetylcholine was decreased.Periodontitis or HC diet alone decreased the expression of peNOS and HC diet increased the expression of iNOS. In contrast, no additive or synergistic effects were found in vascular reactivity or in platelet aggregation when the two conditions were associated (HC + Perio group). Conclusion:Hypercholesterolemia accelerated the process of bone loss induced by periodontitis while a high cholesterol diet or periodontitis individually increased

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Section: Discussionmentioning

confidence: 92%

Section: Discussionmentioning

confidence: 99%

Section: Discussionmentioning

confidence: 99%

See 1 more Smart Citation

Periodontal status, vascular reactivity, and platelet aggregation changes in rats submitted to hypercholesterolemic diet and periodontitis

Silva

Motta

Soares

et al. 2020

J of Periodontal Research

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“…Anti-TNF-α treatment with etanercept also suppresses cerebral damage caused by middle cerebral artery occlusion/reperfusion in both normal and diabetic rats (76). Furthermore, the inhibition of TNF-α production by a thalidomide analog decreases triglyceride levels and increases high-density lipoprotein levels in rats fed hypercholesterolemic diets (77). …”

Section: Pathophysiology Of Comorbiditymentioning

confidence: 99%

Cardiovascular and Metabolic Diseases Comorbid with Psoriasis: Beyond the Skin

et al. 2017

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A close association of systemic inflammation with cardiovascular diseases and metabolic syndrome is recently a popular topic in medicine. Psoriasis is a chronic inflammatory skin disease with a prevalence of approximately 0.1-0.5% in Asians. It is characterized by widespread scaly erythematous macules that cause significant physical and psychological burdens for the affected individuals. The accelerated inflammation driven by the TNF-α/IL-23/IL-17A axis is now known to be the major mechanism in the development of psoriasis. Psoriasis is not a mere skin disease; it is significantly associated with cardiovascular diseases and metabolic syndrome, which suggests that the chronic skin inflammation extends the systemic inflammation beyond the skin. In this article, we review the epidemiological and pathological aspects of psoriasis and its comorbidities.

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“…CC-10004 was synthesized and developed as an oral treatment for psoriasis [ 25 ]. (2-[4-(Methyl-thio)phenyl]isoindoline-1,3-dione) and LASSBio-1425 have been reported as promising anti-inflammatory agents by interrupting TNF-α [ 26 , 27 ]. Strong evidence given by these studies is that the aryl- group and phthalimide are needed for anti-inflammatory activity in psoriasis.…”

Section: Introductionmentioning

confidence: 99%

Synthesis and Biological Evaluation of Thalidomide Derivatives as Potential Anti-Psoriasis Agents

Tang

Lin

Chen

et al. 2018

IJMS

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Several thalidomide derivatives were synthesized and evaluated for their anti-inflammatory activity. Introduction of the benzyl group to the parent thalidomide is unfavorable in which 2-(1-benzyl-2,6-dioxopiperidin-3-yl)isoindoline-1,3-dione (4a) was inactivated. However, the inhibitory activities on TNF-α and IL-6 expression in HaCaT cells were improved by the substitution of a chloro- or methoxy- group at the phenyl position of 4a. The IL-6 inhibitory activity decreased in an order of 5c (69.44%) > 4c (48.73%) > 6c (3.19%) indicating the 3-substituted derivative is more active than the 4-substituted counterpart, which in turn is more active than the 2-substituted counterpart. Among them, 2-[1-(3-chlorobenzyl)-2,6-dioxopiperidin-3-yl]isoindoline-1,3-dione (5c) was found to inhibit TNF-α and IL-6 expression in HaCaT cells with a higher potency than thalidomide and no significant cell cytotoxicity was detected at 10 μM. In psoriasis, Compound 5c reduced IL-6, IL-8, IL-1β and IL-24 in imiquimod-stimulated models. Our results indicated that compound 5c is a potential lead of novel anti-psoriasis agents. Structural optimization of compound 5c and its in vivo assay are ongoing.

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LASSBio-1425, an analog of thalidomide, decreases triglyceride and increases HDL cholesterol levels by inhibition of TNF-α production

Cited by 9 publications

References 9 publications

Periodontal status, vascular reactivity, and platelet aggregation changes in rats submitted to hypercholesterolemic diet and periodontitis

Periodontal status, vascular reactivity, and platelet aggregation changes in rats submitted to hypercholesterolemic diet and periodontitis

Cardiovascular and Metabolic Diseases Comorbid with Psoriasis: Beyond the Skin

Synthesis and Biological Evaluation of Thalidomide Derivatives as Potential Anti-Psoriasis Agents

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