title: Anti-atherogenic effects of a new thienylacylhydrazone derivative, LASSBio-788, in rats fed a hypercholesterolemic diet.
abstract: The compound LASSBio-788 (N-Allyl (2-thienylidene) 3,4-methylenedioxybenzoylhydrazine) is a thienylacylhydrazone derivative shown to have antiplatelet, vasodilatory, and anti-inflammatory properties in vitro. We hypothesize that LASSBio-788 may exert beneficial effects on atherosclerosis. Male wistar rats were divided into 4 groups: Control group received standard rat chow, hypercholesterolemic group (HC) and HC+788 (compound LASSBio-788 group) received hypercholesterolemic diet for 45 days. HC+788 group received compound LASSBio-788 (100 μmol/kg) once daily in the last 15 days. LASSBio-788 reduced the levels of total cholesterol (109.1 ± 4.3 vs. 361.0 ± 12.8 mg/dl), triglycerides (66.1 ± 1.1 vs. 186.9 ± 17.7 mg/dl), LDLc (63.2 ± 6.1 vs. 330.9 ± 9.7 mg/dl), VLDLc (9.8 ± 1.1 vs. 45.0 ± 4.6 mg/dl) and malondialdehyde (4.8 ± 0.3 vs. 9.4 ± 0.5 nmol/ml) compared to the HC group. LASSBio-788 presented antiplatelet properties and decreased inflammatory markers levels. LASSBio-788 promoted a decrease in contractile response to phenylephrine and an improvement in endothelium-dependent vasorelaxant response by increasing two-fold the expression of nitric oxide synthase (eNOS). Our results suggest that the compound LASSBio-788 represents a new multi-targeted drug candidate for the treatment of atherosclerosis.
authors.affiliation: Laboratory of Experimental Pharmacology (LAFE), Department of Physiology and Pharmacology, Biomedical Institute, Fluminense Federal University (UFF), Brazil.
authors.forename: Nadia Alice Vieira
authors.initials: NA
authors.lastname: da Motta
authors.forename: Arthur Eugen
authors.initials: AE
authors.lastname: Kümmerle
authors.forename: Elisabeth
authors.initials: E
authors.lastname: Marostica
authors.forename: Caroline Fernandes
authors.initials: CF
authors.lastname: Dos Santos
authors.forename: Carlos Alberto Manssour
authors.initials: CA
authors.lastname: Fraga
authors.forename: Eliezer Jesus
authors.initials: EJ
authors.lastname: Barreiro
authors.forename: Ana Luisa Palhares
authors.initials: AL
authors.lastname: de Miranda
authors.forename: Fernanda Carla Ferreira
authors.initials: FC
authors.lastname: de Brito
mesh_terms: D000818:Animals; D050197:Atherosclerosis / Q000097:blood / Q000188:drug therapy* / Q000209:etiology*; D008078:Cholesterol, LDL / Q000097:blood; D015243:Cholesterol, VLDL / Q000097:blood; D004036:Diet, Atherogenic / Q000009:adverse effects*; D004195:Disease Models, Animal; D006835:Hydrazones / Q000008:administration & dosage / Q000494:pharmacology / Q000627:therapeutic use*; D008297:Male; D008315:Malondialdehyde / Q000097:blood; D058990:Molecular Targeted Therapy; D019001:Nitric Oxide Synthase / Q000097:blood; D051381:Rats; D017208:Rats, Wistar; D013876:Thiophenes / Q000008:administration & dosage / Q000494:pharmacology / Q000627:therapeutic use*; D014280:Triglycerides / Q000097:blood
chemical_list: D008078:Cholesterol, LDL; D015243:Cholesterol, VLDL; D006835:Hydrazones; C503361:LASSBio-788; D013876:Thiophenes; D014280:Triglycerides; D008315:Malondialdehyde; D019001:Nitric Oxide Synthase