Six-Month Toxicity Study of Oral Administration of D-003 in Sprague Dawley Rats

Gámez, Rafael; Más, Rosa; Noa, Miríam; Menéndez, Roberto; Garcı́a, Hilda; González, Jorge E.; Pérez, Yohani; Goicochea, Eddy

doi:10.2165/00126839-200203060-00002

Cited by 11 publications

(3 citation statements)

References 41 publications

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“…The reason for the increased body weight of the satellite 1000 mg/kg bw group is still uncertain. The weight gain of the satellite 1000 mg/kg bw group in this current study was still in a normal range [20]. A possible explanation is as follows: tamarind pulp water extract has an effect of inhibition of weight gain [16].…”

Section: Discussionmentioning

confidence: 89%

Six-Month Chronic Toxicity Study of Tamarind Pulp (Tamarindus indica L.) Water Extract

et al. 2017

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Tamarind water extract has been shown to demonstrate an anti-obesity effect. In this research, long-term use of tamarind pulp water extract safety was evaluated. Tamarind pulp was extracted by reflux method, followed by freeze-drying to obtain dry extract. Wistar rats were divided into six groups, with 20 animals of each sex per group. The control group and satellite control group received carboxymethylcellulose sodium (CMC-Na) 0.5% 1 mL/100 g bw (body weight) per day. Treatment groups received tamarind pulp extract at doses of 75, 200, 1000, satellite 1000 mg/kg bw per day for six months. After six months, control groups and the treatment group were sacrificed. Satellite groups were sacrificed one month later. Relative organ weights, hematology and clinical biochemistry profiles were determined. After six months, there were no significant change in body weight, hematologic, and clinical biochemistry profiles of the tested group. Body weight of male rats in the satellite 1000 mg/kg bw group was significantly increased in week 30 compared to the satellite control group (p < 0.05). The relative spleen weight of female rats of the 200 mg/kg bw group was reduced (p < 0.05). The relative kidney weight of male rats in the 1000 mg/kg bw group was increased (p < 0.05). This study showed that tamarind pulp extract was generally safe and well tolerated at the tested dose.

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Section: Discussionmentioning

confidence: 89%

Six-Month Chronic Toxicity Study of Tamarind Pulp (Tamarindus indica L.) Water Extract

et al. 2017

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“…Thus, the negative contribution of D-003 for reinforcing the mechanisms of liver toxicity induced with galactosamine is consistent with its lack of hepatotoxicity found in previous toxicological studies. 43,44 In such regard, the fact that D-003 can protect from liver damage induced by agents increasing LP processes is interesting, since it is uncommon for cholesterol-lowering drugs, associated with increases of transaminases and others features indicative of liver toxic- ity. Thus, a cholesterol-lowering drug devoid of liver toxicity is promising for treating patients with hypercholesterolemia at high coronary risk, but difficult to manage with drug therapy due to disturbances of liver function.…”

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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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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“…Previous studies of oral toxicity of D-003 in rodents (acute, subchronic, and chronic) have shown that it did not induce drug-related toxicity. [18][19][20] Similarly, the in vitro and in vivo assessment of cytotoxic and/or genotoxic potential effects of D-003 showed that D-003 was devoid of cytotoxic or genotoxic potential, 21,22 and the lack of reproductive toxicity has been also documented for D-003. 23 Nevertheless, information about putative drug-to-drug interactions between D-003 and other drugs commonly consumed is scarce, being limited to isolated experiences of pharmacodynamic interactions.…”

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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Six-Month Toxicity Study of Oral Administration of D-003 in Sprague Dawley Rats

Abstract: It was concluded that the highest studied dose of D-003 (1,000 mg/kg/day) represented a non-toxic dose level in the present chronic toxicity study in rats.

Cited by 11 publications

References 41 publications

Six-Month Chronic Toxicity Study of Tamarind Pulp (Tamarindus indica L.) Water Extract

Six-Month Chronic Toxicity Study of Tamarind Pulp (Tamarindus indica L.) Water Extract

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

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

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