Anti-atherogenic Effects of a New Thienylacylhydrazone Derivative, LASSBio-788, in Rats Fed a Hypercholesterolemic Diet

Abstract

Abstract. The compound LASSBio-788 (N-Allyl (2-thienylidene) 3,4-methylenedioxybenzoylhydrazine) is a thienylacylhydrazone derivative shown to have antiplatelet, vasodilatory, and antiinflammatory 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 mmol/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.

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

“…Platelet aggregation was evaluated by the turbidimetric method using a platelet lumi‐aggregometer (Model 560CA; Chrono‐log Corporation, Havertown, PA, USA) following the protocol described by da Motta et al Briefly, rat blood was collected by cardiac puncture into 3.8% trisodium citrate (9:1 v/v). PRP was obtained by centrifugation at 250 g for 10 min at 37°C under continuous stirring.…”

“…The vascular reactivities to phenylephrine and acetylcholine were determined according to a protocol previously published by da Motta et al Briefly, rat thoracic aorta rings with functional endothelium obtained from the different experimental groups were pre‐contracted with phenylephrine (1 µmol/L) and cumulative curves of acetylcholine (10 −9 to 10 −4 mol/L) to induced relaxation were obtained and expressed as percentage change to phenylephrine contraction for each group. Cumulative concentration‐response curves to phenylephrine (10 −9 to 10 −4 mol/L) were also obtained.…”

Cilostazol exerts antiplatelet and anti‐inflammatory effects through AMPK activation and NF‐kB inhibition on hypercholesterolemic rats

“…The HCD was prepared following the method of Ramesh et al, [19,20] by mixing equal quantities of a commercial standard chow (Nuvilab â , Curitiba, Paran a, Brazil) and hypercholesterolemic constituents. The rats were randomly divided into three groups, each of which contained 10 animals.…”

“…once a day for 15 days. The HCD was prepared following the method of Ramesh et al, [19,20] by mixing equal quantities of a commercial standard chow (Nuvilab â , Curitiba, Paran a, Brazil) and hypercholesterolemic constituents. The final form of the HCD contained 5% cholesterol, 20% sucrose, 2% sodium cholate, 20% lactose, 0.4% choline chloride, 0.15% thiouracil (Sigma-Aldrich), and 20% hydrogenated vegetable oil and was mixed with an equal quantity (w/w) of the commercial standard chow.…”

Synthesis, Molecular Modeling, and Evaluation of Novel Sulfonylhydrazones as Acetylcholinesterase Inhibitors for Alzheimer's Disease

“…Although sulfonylhydrazones and N ‐acylhydrazones are associated to toxicity in vivo , the literature describes some examples of bioactive compounds possessing this moiety which proved to be stable in vivo and in vitro . Moreover, nitrogen accompanied by an electronegative group tends to be more stable since it may participate in the conjugation of the imine double bond.…”