Effects of D-003, a New Hypocholesterolaemic and Antiplatelet Compound, on Lipid Profile and Lipid Peroxidation in Healthy Volunteers

Castaño, Gladys; Menéndez, Roberto; Más, Rosa; Ledón, Nuris; Fernández, Julio César; Pérez, Julio C.; González, Rafael de Miguel; Lezcay, Magnolia

doi:10.2165/00044011-200323030-00005

Cited by 22 publications

(26 citation statements)

References 41 publications

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“…29,30 D-003 lowers cholesterol through inhibition of cholesterol biosynthesis between acetate consumption and mevalonate production involving an indirect regulation, not a direct competitive inhibition, of HMG-CoA reductase enzyme activity. 31 Likewise, D-003 inhibits platelet aggregation and susceptibility of LDL molecules to undergo LP, as supported by experimental [32][33][34] and clinical [35][36][37][38] data. In particular, inhibitory effects of D-003 on LP have been connected with some pleiotropic extravascular mechanism, like preventive effects on liver damage induced with CCl 4 or paracetamol in Sprague-Dawley rats.…”

Section: Introductionmentioning

confidence: 73%

“…[16][17][18][19][20][21][22][23][24] In fact, the hypothesis underlying the rationale for investigating the putative protection of D-003 on the liver damage induced with both paracetamol and CCl 4 was based in the effective antioxidant profile of D-003 to prevent LP induced with several agents in rats 34 and humans. 38 The lack of efficacy of D-003 against the liver damage induced with galactosamine is a new piece of evidence to connect the hepatoprotective and antioxidant effects of D-003. Thus, as LP is not relevant to galactosamine hepatotoxicity, it is logical that D-003 has not been effective, which is different from what occurs in CCl 4 -and paracetamol-induced liver damage.…”

Section: Discussionmentioning

confidence: 99%

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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

Noa

Mendoza

Más

et al. 2005

Journal of Medicinal Food

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D-003 is a mixture of very-high-molecular-weight aliphatic primary acids purified from sugar cane wax, wherein octacosanoic acid is the most abundant. Experimental and clinical studies have shown that D-003 lowers cholesterol and prevents plasma lipoprotein peroxidation (LP). D-003 has protected against the histological changes characteristic of CCl4- and paracetamol-induced hepatic injury in rats, in which LP plays a pivotal role for explaining the resulting hepatotoxicity. Galactosamine induces hepatotoxicity associated with depressed RNA and protein synthesis, not with LP. The aim of this study was to evaluate whether D-003 could prevent hepatoxicity induced by mechanisms others than increased LP. We investigated the effects on galactosamine hepatotoxicity in rats distributed into five groups: a negative control group, a positive control group, 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 were sacrificed, and livers were immediately removed for histopathological studies. Livers from positive controls showed the characteristic pattern of galactosamine-induced damage. Galactosamine significantly reduced the percentage of normal hepatocytes, increasing both necrotic or lipid-rich hepatocytes compared with negative controls. D-003, however, did not increase the percentage of normal hepatocytes compared with positive controls, indicating that treatment was not effective for preventing 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 of galactosamine-induced hepatotoxicity.

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Section: Introductionmentioning

confidence: 73%

Section: Discussionmentioning

confidence: 99%

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

Noa

Mendoza

Más

et al. 2005

Journal of Medicinal Food

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“…The second study was a double-blind, randomized, placebo-controlled trial in 46 healthy volunteers [25]. D-003 (5 and 10 mg/day) for 8 weeks led to results similar to the first trial.…”

Section: Evidence From Clinical Studiesmentioning

confidence: 85%

“…Castano et al [24,25] investigated the cholesterol-lowering effects of D-003 in healthy volunteers in two trials. The first was a single-blind, randomized, placebocontrolled, parallel trial conducted in 2002 and included 38 subjects [24].…”

Section: Evidence From Clinical Studiesmentioning

confidence: 99%

D-003 (Saccharum officinarum): The forgotten lipid-lowering agent

Awad

Penson

Banach

2016

Pharmacological Research

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ABSTRACT:Reduction of elevated cholesterol levels, particularly low-density lipoprotein cholesterol (LDL-C), is essential in primary and secondary prevention of cardiovascular disease (CVD). Therefore there is still a large need for new effective drugs, which would be able to essentially reduce LDL-C and in the consequence CV residual risk.D-003 is a mixture of high aliphatic primary acids purified from sugarcane (Saccharum officinarum) wax. It showed promising hypocholesterolemic effects in both animal and human studies; it significantly lowers both serum total cholesterol (TC) and LDL-C, and increases high-density lipoprotein cholesterol (HDL-C). In addition, it showed a favorable safety profile. In this review, we evaluated the profile of D-003 as a lipid-lowering agent based on data from available preclinical and clinical studies.

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“…[6][7][8][9] Also, D-003 administered from 5 to 50 mg/day has shown cholesterol-lowering effects in healthy volunteers and patients with Type II hypercholesterolemia causing reduction of serum LDL-C and TC, while markedly raising HDL-C. [10][11][12] On the other hand, D-003 orally administered also induces anti-platelet effects in animal models and human beings, [12][13][14][15][16][17] which appears to be mediated through reduced thromboxane A 2 levels and increased prostacyclin values. 15,16 Thus, D-003 shows a pharmacological profile suggesting that it could be a promising agent for treating atherothrombotic diseases, as expected from its cholesterol-lowering and anti-platelet effects.…”

Section: Introductionmentioning

confidence: 99%

Effects of D-003 on Hepatic Drug-Metabolizing Enzyme Activities in Rats

Gámez

Rodeiro

González

et al. 2004

Journal of Medicinal Food

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D-003 is a mixture of very-long-chain aliphatic acids with cholesterol-lowering and concomitant anti-platelet effects. The microsomal cytochrome P-450 system comprises a superfamily of proteins present in hepatic and extrahepatic tissues that is responsible for the metabolism of many drugs. The present study was undertaken to investigate the effects of D-003 on in vivo drug-metabolizing hepatic enzymes. Two experimental series (n = 6 animals/group) were performed. In the first series rats were randomly distributed in one control and two groups treated with D-003 at 1,000 and 2,000 mg/kg for 14 days. In the second one they were distributed in one control and three groups treated with D-003 (250, 500, and 1,000 mg/kg) for 6 months. All treatments were orally administered by gastric gavage. Control rats were orally treated only with acacia gum/water vehicle. The content of microsomal P-450, b (5) cytochromes, total sulfhydryl groups, nonprotein sulfhydryl groups, and protein-bound sulfhydryl groups as well as the activities of NADPH cytochrome c reductase, aminopyrine demethylase, dimethylnitrosamine N-demethylase, 7-ethoxyresorufin O-deethylation, 7-pentoxyresorufin O-depentylation, and cytosolic glutathione S-transferase were assessed. D-003 administered up to 2,000 mg/kg or 1,000 mg/kg during 14 days or 6 months did not affect the activities of the hepatic drug-metabolizing enzymes investigated. It is concluded that D-003 is not metabolized by the liver cytochrome system and that potential risk derived from drug-to-drug interactions between D-003 and concomitant drugs appears to be low.

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Effects of D-003, a New Hypocholesterolaemic and Antiplatelet Compound, on Lipid Profile and Lipid Peroxidation in Healthy Volunteers

Cited by 22 publications

References 41 publications

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

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

D-003 (Saccharum officinarum): The forgotten lipid-lowering agent

Effects of D-003 on Hepatic Drug-Metabolizing Enzyme Activities in Rats

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