Print Email Facebook Twitter A thirteen week dietary toxicity study with 7-hydroxymatairesinol potassium acetate (HMRlignan) in rats Title A thirteen week dietary toxicity study with 7-hydroxymatairesinol potassium acetate (HMRlignan) in rats Author Lina, B. Korte, H. Nyman, L. Unkila, M. TNO Kwaliteit van Leven Publication year 2005 Abstract Plant lignan 7-hydroxymatairesinol (7-HMR) is a novel precursor of the mammalian lignan enterolactone. A 13 week toxicity study at dietary levels of 0, 0.25, 1, and 4% (w/w) of potassium acetate complex of 7-HMR (HMRlignan) was conducted in the Wistar rat. These dietary levels resulted in an average daily intake of 160, 640, and 2600 mg HMRlignan/kg body weight/day, respectively. A considerable systemic exposure of HMRlignan was verified by dose-related increases in plasma total (conjugated and unconjugated) concentration of 7-HMR and metabolites enterolactone, 7-hydroxyenterolactone, and matairesinol. Enterolactone appeared to be the major metabolite. Most (>96%) of the circulating 7-HMR and enterolactone was in conjugated form as measured from the low-dose rat plasma samples. HMRlignan exposure did not significantly affect clinical signs, ophthalmoscopy or neurobehavioural observations, and motor activity. Transient reductions in food intake and body weight gain in the mid-and high-dose group were ascribed to decreased palatability of the test feed. Only in males of the high-dose group the body weights remained slightly reduced throughout the study. In the high-dose group the number of thrombocytes (females), and total white blood cell count (males) were increased. Plasma triglycerides were dose-dependently depressed in males of all test groups and in females of the mid- and high-dose group, while plasma total cholesterol, and phospholipids were decreased in high-dose males. These changes, which have also been reported for other (flaxseed) lignans, were not considered to represent adverse effects. The relative weight of the kidneys was increased in males of the high-dose group. The weight of the full and empty caecum showed dose-related increases in males of all treatment groups and in females of the high-dose group. Absolute ovary weights were decreased in all treatment groups while decreases in relative ovary weights were confined to the mid- and high-dose group. In addition, a marginal lengthening of the estrus cycle was noted in high-dose females. Apart from prevention of hyaline droplet nephropathy in all high-dose male rats, there were no treatment-related histopathological alterations. It was concluded that HMRlignan showed weak antiestrogen-like activity which may be mediated through enterolactone metabolite. Based on declined ovary weight, the no observed adverse effect level of HMRlignan was set at 0.25% in feed corresponding to 160 mg/kg body weight/day. © 2004 Elsevier Inc. All rights reserved. Subject Toxicology BiologyToxicology and Applied Pharmacology7-HydroxymatairesinolEnterolactoneLignanSafetySub-chronicToxicity7 hydroxyenterolactone7 hydroxymatairesinol potassium acetatedrug metaboliteenterolactonelignanmatairesinolphospholipidtriacylglycerolunclassified druganimal experimentanimal tissuearticlebody weightcholesterol blood levelchronic toxicitycognitioncontrolled studydietdose responsedrug blood levelestrus cyclefemalefood intakehistopathologykidney diseaseleukocyte countmalemotor activitynonhumanophthalmoscopyorgan weightovarypalatabilitypriority journalratsex differencethrombocyte counttoxicity testingtriacylglycerol blood levelweight reduction4-ButyrolactoneAnimalsBody WeightDietFemaleLignansMaleMotor ActivityNo-Observed-Adverse-Effect LevelOrgan SizePotassium AcetateRatsRats, WistarMammaliaRattus norvegicus To reference this document use: http://resolver.tudelft.nl/uuid:e16f2f06-8fd0-44ba-9d6f-87eb65bc1085 DOI https://doi.org/10.1016/j.yrtph.2004.09.001 TNO identifier 238314 ISSN 0273-2300 Source Regulatory Toxicology and Pharmacology, 41 (1), 28-38 Document type article Files To receive the publication files, please send an e-mail request to TNO Library.