Preliminary evaluation of the cytotoxic and genotoxic potential of D-003: Mixture of very long chain fatty acids.
D-003 is a mixture of very long chain aliphatic acids purified from sugar cane wax, wherein octacosanoic acid represents the major component. Previous experimental studies have shown that D-003 inhibits platelet aggregation in rodents. Also, its lowers total (TC) and low-density lipoprotein cholesterol (LDL-C) in normocholesterolemic rabbits in a dose-dependent manner and inhibits cholesterol biosynthesis in fibroblast cultures. The present study was performed to investigate the in vitro cytotoxic and genotoxic potential effects of D-003 assessed through two tests: the neutral red (NR) assay and the Ames test. Positive and negative controls were included in each experimental series. Compared with controls, no cytotoxicity was evident after 24 and 72 h of treatment with doses up to 1,000 microg/ml in the NR assay. On the other hand, D-003 (5-5,000 microg/plate) did not increase the frequency of reverse mutations in the Ames test in both alternatives with or without S9 mix metabolic activation and a pre-incubation step. The positive control chemicals included in each experiment, namely, treatment with sodium dodecyl sulphate (SDS) in the NR assay and sodium azide (NaAz), 2-aminofluorene (AF), and dimethylnitrosamine (DMNA) in the Ames test, induced the expected changes, such as a decrease in optical density (OD) values in the NR assay and an increase in the frequency of reverse mutations in the Ames test. The present results indicate that D-003 did not show evidence of cytotoxic or genotoxic potential in tests able to detect the ability of chemicals to disrupt cells (NR assay) or to induce gene mutations (Ames test).
Gámez
Rafael
R
Pharmacology and Toxicology Department, Center of Natural Products, National Center for Scientific Research, Havana, Cuba. dalmer@etecsa.ip.cu
Rodeiro
Idania
I
Fernández
Ivonne
I
Acosta
Pilar Caridad
PC
D016475:3T3 Cells; D000818:Animals; D004305:Dose-Response Relationship, Drug; D005227:Fatty Acids / Q000009:adverse effects* / Q000378:metabolism; D007202:Indicators and Reagents / Q000494:pharmacology; D051379:Mice; D009152:Mutagenicity Tests; D009154:Mutation; D009499:Neutral Red / Q000494:pharmacology; D010975:Platelet Aggregation Inhibitors / Q000009:adverse effects*; D012486:Salmonella typhimurium / Q000378:metabolism; D013997:Time Factors
C418063:D-003 sugarcane wax acid mixture; D005227:Fatty Acids; D007202:Indicators and Reagents; D010975:Platelet Aggregation Inhibitors; D009499:Neutral Red; C068792:octacosanoic acid