Effect of D-003 on Intimal Thickening and Circulating Endothelial Cells in Rabbit Cuffed Carotid Artery

Miriam Noa,Sarah? Mendoza,Rosa M?s 한국식품영양과학회 2005 Journal of medicinal food Vol.8 No.2

D-003 is a mixture of very-high-molecular-weight aliphatic primary acids purified from sugar-cane (Saccha-rum officinarumL.) wax, in which octacosanoic acid is the most abundant component. Previous experimental studies haveshown that D-003 not only shows cholesterol-lowering and anti-platelet effects, but also reduces thromboxane B2 and in-creases prostacyclin levels. It acts by inhibiting cholesterol biosynthesis. The positioning of a non-occlusive silicone collararound the rabbit carotid artery results in the formation of a neointima. Collars were placed around the left carotid for 15 days.The contralateral artery was sham-operated. We included three experimental groups: A control group received vehicle, andtwo others received D-003 at 5 and 25 mg/kg until sacrificed. Samples of arteries were examined by light microscopy. Toevaluate intimal thickening the cross-sectional areas of intima and media were measured. Neointima was significantly reducedin D-003-treated animals compared with controls. Furthermore, the circulating endothelial cell has been studied in this ex-perimental model with endothelium damage. The results demonstrate the protective effect of D-003 on vascular endotheliumof the studied rabbits. It is concluded that the protective effect of D-003 against neointima formation and circulating endothelialcells in this experimental model could represent potential beneficial pleiotropic effects in the anti-atherogenic profile of thissubstance, beyond its cholesterol-lowering and anti-platelet effects independently demonstrated.

Lack of Protective Effect of D-003, a Mixture of High-Molecular-Weight Primary Acids from Sugar Cane Wax, on Liver Damage Induced by Galactosamine in Rats

Miriam Noa,Sarah Mendoza,Rosa Mas,Nilda Mendoza 한국식품영양과학회 2005 Journal of medicinal food Vol.8 No.3

D-003 is a mixture of very-high-molecular-weight aliphatic primary acids purified from sugar cane wax, whereinoctacosanoic acid is the most abundant. Experimental and clinical studies have shown that D-003 lowers cholesterol and pre-vents plasma lipoprotein peroxidation (LP). D-003 has protected against the histological changes characteristic of CCl4- andparacetamol-induced hepatic injury in rats, in which LP plays a pivotal role for explaining the resulting hepatotoxicity. Galac-tosamine induces hepatotoxicity associated with depressed RNA and protein synthesis, not with LP. The aim of this studywas to evaluate whether D-003 could prevent hepatoxicity induced by mechanisms others than increased LP. We investigatedthe effects on galactosamine hepatotoxicity in rats distributed into five groups: a negative control group, a positive controlgroup, and three groups treated with galactosamine and D-003 (5, 25, and 100 mg/kg). To induce liver damage, galactosamine(800 mg/kg) was injected intraperitoneally 30 minutes after dosing with vehicle or D-003. Twenty-four hours later, rats weresacrificed, and livers were immediately removed for histopathological studies. Livers from positive controls showed the char-acteristic pattern of galactosamine-induced damage. Galactosamine significantly reduced the percentage of normal hepato-cytes, increasing both necrotic or lipid-rich hepatocytes compared with negative controls. D-003, however, did not increasethe percentage of normal hepatocytes compared with positive controls, indicating that treatment was not effective for pre-venting the hepatic injury induced with galactosamine. Likewise, D-003 failed to change the content of necrotic and lipid-rich hepatocytes relative to positive controls. It is concluded that D-003 did not protect against the histological changes ofgalactosamine-induced hepatotoxicity.

Protective Effect of Policosanol on Endothelium and Intimal Thickness Induced by Forceps in Rabbits

Miriam Noa,Rosa Mas,Carlos Lariot 한국식품영양과학회 2007 Journal of medicinal food Vol.10 No.3

Presented at the XIIth International Symposium onDrugs Affecting Lipid Metabolism, Baylor University, Houston,1995.44. Pomerantz KB, Hajjar DP: Eicosanoids in regulation of arterialsmooth muscle cell phenotype, proliferative, capacity and cho-lesterol metabolism. Arteriosclerosis1989;9:413429.45. Menndez R, Fraga V, Amor AM, Gonzlez RM, Ms R: Oraladministration of policosanol inhibits in vitro copper ion-inducedrat lipoprotein peroxidation. Physiol Behav1999;67:17.46. Menndez R, Ms R, Amor AM, et al.: Effects of policosanoltreatment on the susceptibility of low density lipoprotein (LDL)isolated from healthy volunteers to oxidative modification in vitro.Br J Clin Pharmacol2000;50:255262.47. Matrisian LM: The matrix degrading metalloproteinases. Bioes-says1992;14:455463.48. Bennett M, Evan G, Schwartz S: Apoptosis of human vascularsmooth muscle cells derived from normal vessels and coronaryatherosclerotic plaques. J Clin Invest1995;95:22662274.POLICOSANOL ON INTIMA OF ARTERIES IN RABBITS 45949. Angelini A, Visona A, Pettenazzo E, Calabrese F, Yacoub A: Pro-liferation and cellular death (apoptosis) in an animal model of ac-celerated atherosclerosis. Atherosclerosis1997;134:267276.50. Br PR: Apoptosisthe cell’s silent exit. Life Sci1996;59:

Effect of D-003, a Mixture of Very-Long-Chain Aliphatic Acids Purified from Sugarcane Wax, on Cerebral Ischemia in Mongolian Gerbils

Vivian Molina,Miriam Noa,Lourdes Arruzazabala,Daisy Carbajal,Rosa M? 한국식품영양과학회 2005 Journal of medicinal food Vol.8 No.4

D-003 is a mixture of very-high-molecular-weight aliphatic acids purified from sugar cane wax (Saccharumofficinarum), which inhibits platelet aggregation and lipid peroxidation. The objective of the present study was to evaluatethe effect of D-003 on cerebral ischemia induced by ischemia-reperfusion (I-R) in Mongolian gerbils. Two experimental se-ries were conducted. The first series investigated the effects of D-003 on cerebral edema, neurological symptoms, and mor-tality in Mongolian gerbils with cerebral ischemia induced by I-R, while the second series investigated the effects on histo-logical markers of cerebral injury, such as edema intensity (vacuolization) and cerebral necrosis. Animals were randomlydistributed in five experimental groups: a sham-operated group experiencing surgical handling except the clamping and orallytreated with Tween/water vehicle and four groups subjected to the I-R surgical procedure. One of these groups was treatedwith the same vehicle, and the other three groups received D-003 at 25, 100, and 200 mg/kg, respectively. All treatments wereadministered for 14 days. D-003 (200 mg/kg) significantly reduced the cerebral edema and clinical symptoms provoked by I-R compared with the positive control group, whereas lower doses (25 and 100 mg/kg) were not effective. Positive controlanimals showed an injury profile characterized by swelling (tissue vacuolization) and necrosis of neurons in all areas of thebrain studied (frontal cortex, hippocampus, and striatum). The results of the histological study were consistent with those ob-served by determining cerebral edema and symptoms observation. Thus, D-003 at 200 mg/kg significantly reduced histolog-ical markers of brain injury (swelling and necrosis) compared with the control group. It is concluded that D-003 administeredorally at 200 mg/kg for 14 days protected against cerebral damage caused by bilateral cerebral ischemia in Mongolian ger-bils.

Preventive Effect of D-002, a Mixture of Long-Chain Alcohols from Beeswax, on the Liver Damage Induced with CCl4 in Rats

Sarahi Mendoza,Miriam Noa,Yohani Perez,Rosa Mas 한국식품영양과학회 2007 Journal of medicinal food Vol.10 No.2

Effect of D-003 on Isoproterenol-Induced Myocardial Necrosis in Rats

Daisy Carbajal,Miriam Noa,Vivian Molina,Maria Lourdes Arruzazabala,Rosa M?,Sarah?Mendoza,Jorge Gonz?ez 한국식품영양과학회 2003 Journal of medicinal food Vol.6 No.1

D-003 is a mixture of high-molecular-weigh t aliphatic primary acids purified from sugar canewax with antiplatelet and cholesterol-lowering effects. Cardiac lesions induced by isopro-terenol (ISO) are characterized by myocardial necrosis and exudative infiltration. The objec-tive of this study was to determine whether D-003 shows protective effects against ISO-in-duced myocardial necrosis in rats. Effects of orally administered single doses of D-003 (25 40mg/kg) and acetylsalicylic acid (ASA, 30 mg/kg), as well as repeated doses of D-003 (5 20mg/kg), on characteristic markers of ISO-induced myocardial necrosis in rats were investi-gated. D-003 administered as single doses dose-dependen tly decreased necrosis area, percentof infarct area, and the presence of polymorphonuclear cells (PMNs) in myocardial tissue, butonly the reductions induced by 200 and 400 mg/kg were significant. Oral acute treatment withASA also decreased necrosis area and percent of infarct area, but the occurrence of PMNs wasunchanged. D-003 administered repeatedly for 10 days also decreased all myocardial necro-sis indicators in a dose-dependen t maner, with results effective from 25 mg/kg to the high-est dose tested, indicating that the repeated dose scheme was more effective to prevent thedamage. It is concluded that D-003 shows a protective effect on the myocardial necrosis in-duced by ISO in rats.13

Effects of In Utero Exposure to D-004, a Lipid Extract from Roystonea regia Fruits, in the Male Rat: A Comparison with Finasteride

Ariadne Gutie´rrez Martı´nez,Balia Pardo,Rafael Ga´mez,Rosa Mas,Miriam Noa,Gisela Marrero,Maikel Valle,Haydee Garcı´a,Dayisell Curveco,Nilda Mendoza,Edy Goicochea 한국식품영양과학회 2011 Journal of medicinal food Vol.14 No.12

D-004 is a lipid extract obtained from Cuban royal palm fruits, consisting of a mixture of free fatty acids, that prevents prostate hyperplasia induced with testosterone in rodents. This study investigated the possible alterations due to D-004 of androgen-dependent development after exposure in utero and compared them with those due to finasteride. Rats were randomized into five experimental groups: a control group, three groups treated with D-004 at 500, 750, or 1,000 mg/kg/day,respectively, and a group treated with finasteride (10 mg/kg/day). Male rats were treated 10 weeks before and during mating. Female rats were treated for 15 days prior mating, during mating, during pregnancy, and until lactation (day 21) except for those treated with finasteride, which were only administered the drug on gestational days 12–21. All male offspring were monitored individually until necropsy after postnatal day 90. The results of the present study indicate that D-004 induced no alterations in androgen-dependent development after the exposure in utero. Also, the current study demonstrated a permanent reduction in anogenital distance and retention of nipples in adult male rats exposed to finasteride during late gestation. Significant alterations induced by exposure to finasteride were mainly in tissues dependent on dihydrotestosterone during development.