ABSTRACT
Lycopene, as a suspension in sunflower oil (20% w/w), was tested for subchronic toxicity by administration at dietary concentrations of 0, 0.25, 0.50, and 1.0% to groups of 20 male and 20 female Wistar rats for a period of 90 days. The lycopene examined in this study was derived from a fungal biomass (Blakeslea trispora). Lycopene intake was calculated to be 0, 145, 291, and 586mg/kg body weight/day in control through high-dose males and 0, 156, 312, and 616mg/kg body weight/day in control through high-dose females. The results from this study do not provide any evidence of toxicity of lycopene at dietary levels up to 1.0% as demonstrated by the findings of clinical observations, neurobehavioral observations, motor activity assessment, body weight and food consumption measurements, ophthalmoscopic examinations, hematology, clinical chemistry, urinalysis, organ weights, gross pathology, or histopathology. The No-Observed-Effect Level (NOEL) was 1.0% in the diet, the highest dietary concentration tested.
Subject(s)
Antioxidants/toxicity , Carotenoids/toxicity , Mucorales/metabolism , Administration, Oral , Animals , Antioxidants/administration & dosage , Behavior, Animal/drug effects , Biomass , Body Weight/drug effects , Carotenoids/administration & dosage , Chemistry, Clinical , Diet , Dose-Response Relationship, Drug , Female , Hematologic Tests , Lycopene , Male , Motor Activity/drug effects , Mucorales/chemistry , No-Observed-Adverse-Effect Level , Rats , Rats, WistarABSTRACT
Vasoactive intestinal peptide (VIP) is an important member of the group of neuropeptides that appears to be involved in the regulation of prostatic growth and function. Here we studied VIP receptors in membranes from human benign hyperplastic prostate. Accordingly to observations in rat prostatic membranes, [125I]VIP binding to human prostatic membranes suggested two classes of binding sites with high Kd = 0.22 nM) and low (Kd = 37.7 nM) affinities. VIP bound in human and rat membrane preparations to a common VIP/pituitary adenylate cyclase-activating peptide (PACAP) receptor, as VIP, PACAP-27, and PACAP-38 were equipotent for competition of [125I]VIP binding. A PACAP-preferring receptor appears to be expressed in human prostate, since [125I]PACAP binding was displaced with more potency by PACAP than by VIP, and a messenger RNA corresponding to type I PACAP receptor was found. Cross-linking experiments suggested a VIP receptor of about 71 kDa in human and 52 kDa in rat prostates. The binding of [125I]VIP to membranes and the labeling of the bands observed after electrophoresis were competitively inhibited by GTP, suggesting the coupling of VIP receptors to a G protein. Moreover, after solubilization and cross-linking, we observed a 120-kDa band that corresponded to the VIP receptor-alpha s association. VIP stimulated adenylyl cyclase activity in a dose-dependent manner, but the potency and/or the efficacy of VIP were lower in all human preparations studied than in rat prostatic membranes. In conclusion, this study clearly demonstrates the expression of VIP/PACAP common receptors associated with alpha s protein in human prostate and suggests that these neuropeptides could play an important and complex role in the physiology and pathophysiology of this human gland.
