ABSTRACT
In the search for new potential hypolipidemic agents, the present study focused on the synthesis of 2-acyl phenols (6a-c and 7a-c) and their saturated side-chain alkyl phenols (4a-c and 5a-c), and on the evaluation of their hypolipidemic activity using a murine Tyloxapol-induced hyperlipidemic protocol. The whole series of compounds 4-7 greatly and significantly reduced elevated serum levels of total cholesterol, LDL-cholesterol, and triglycerides, with series 6 and 7 showing the greatest potency ever found in our laboratory. At the minimum dose (25mg/kg/day), the latter compounds lowered cholesterol by 68-81%, LDL by 72-86%, and triglycerides by 59-80%. This represents a comparable performance than that shown by simvastatin. Experimental evidence and docking studies suggest that the activity of these derivatives is associated with the inhibition of HMG-CoA reductase.
Subject(s)
Anisoles/chemistry , Anisoles/pharmacology , Hydroxymethylglutaryl-CoA Reductase Inhibitors/chemical synthesis , Hydroxymethylglutaryl-CoA Reductase Inhibitors/pharmacology , Phenols/chemistry , Phenols/pharmacology , Allylbenzene Derivatives , Animals , Binding Sites , Catalytic Domain , Cholesterol/blood , Cholesterol, LDL/blood , Crystallography, X-Ray , Enzyme Activation/drug effects , Humans , Hydroxymethylglutaryl CoA Reductases/chemistry , Hydroxymethylglutaryl CoA Reductases/metabolism , Hydroxymethylglutaryl-CoA Reductase Inhibitors/metabolism , Male , Mice , Mice, Inbred ICR , Molecular Conformation , Molecular Docking Simulation , Protein Binding , Triglycerides/blood , Weight Gain/drug effectsABSTRACT
Benzo[alpha]pyrene (B[α]P) was used to test the possible antimutagenic effects of Arthrospira (Spirulina) maxima (SP) on male and female mice. SP was orally administered at 0, 200, 400, or 800 mg/kg of body weight to animals of both sexes for 2 weeks before starting the B[α]P (intraperitoneal injection) at 125 mg/kg of body weight for 5 consecutive days. For the male dominant lethal test, each male was caged with two untreated females per week for 3 weeks. For the female dominant lethal test, each female was caged for 1 week with one untreated male. All the females were evaluated 13-15 days after mating for incidence of pregnancy, total corpora lutea, total implants and pre- and postimplant losses. SP protected from B[α]P-induced pre- and postimplant losses in the male dominant lethal test, and from B[α]P-induced postimplantation losses in treated females. Moreover, SP treatment significantly reduced the detrimental effect of B[α]P on the quality of mouse semen. Our results illustrate the protective effects of SP in relation to B[α]P-induced genetic damage to germ cells. We conclude that SP, owing mainly to the presence of phycocyanin, could be of potential clinical interest in cancer treatment or prevention of relapse.
Subject(s)
Antimutagenic Agents/analysis , Benzo(a)pyrene/antagonists & inhibitors , Diet , Spirulina , Abortion, Veterinary/prevention & control , Animals , Antimutagenic Agents/administration & dosage , Breeding , Dietary Supplements , Female , Male , Mice , Mutagenicity Tests , Mutagens , Ovum/drug effects , Phycocyanin/administration & dosage , Pregnancy , Spermatozoa/abnormalities , Spermatozoa/drug effectsABSTRACT
Congenital malformations are one of the major causes of child mortality all over the world. In order to prevent them it is necessary to find substances that act as anti-teratogenic agents. In this study hydroxyurea (HU), an antineoplastic and teratogenic drug, was administered to pregnant mice because one of its major mechanisms of teratogenesis is the production of reactive oxygen species (ROS). The aim of this work was to determine if Spirulina maxima (SP) and its aqueous protein extract could protect against HU-teratogenic insult in mouse embryos. SP has been used for a long time because of its nutritional and pharmacological properties. The antioxidant activity, one of the most important, is related to the protein extract due to its content of phycobiliproteins. It was observed that neither SP nor its extract provoked teratogenic effects at any dose tested and even increased vitelline yolk sac circulation. Dams exposed to HU (30 mg/kg, i.p.) presented embryos with multiple alterations in their development. Groups treated with SP or its extract, before and after HU exposure, showed a protector effect in a dose-dependent manner. TBARS test confirmed that the protection effect was related to the antioxidant activity of both SP and its extract.
