title: Investigation on Toxicity and Teratogenicity in Rats of a Retinoid-Polyamine Conjugate with Potent Anti-Inflammatory Properties.
abstract: Previous studies have shown that N(1),N(12)-bis(all-trans-retinoyl)spermine (RASP), a retinoid analog, inhibits RNase P activity and angiogenesis in the chicken embryo chorioallantoic membrane, demonstrates anti-tumor activity on prostate cancer cells, and acts as anti-inflammatory agent, being more effective and less toxic than all-trans retinoic acid. In an attempt to further characterize the biological profile of RASP, we tested its effects on organ toxicity and teratogenicity by daily oral gavage of RASP at a level of 50 mg/Kg of body weight in two generations of rats. We found that this compound does not induce changes to the body growth, the appearance of physical features, and the animal's reflexes. Additionally, no substantial histopathological lesions were found in brain, heart, lung, thymus, liver, thyroid gland, adrenal gland, pituitary gland, kidneys, spleen, skin, femora, prostate, testis, epididymis, vagina, uterus, and ovaries of RASP-treated animals. These results suggest RASP, as a promising lead compound for the treatment of several dermatological disorders and certain cancer types, has apparently minimal toxic side-effects as revealed in this two-generation reproduction study in rats.
authors.affiliation: Department of Biochemistry, School of Medicine, University of Patras, Patras, Greece.
authors.forename: Theodoros
authors.initials: T
authors.lastname: Petridis
authors.affiliation: Department of Biochemistry, School of Medicine, University of Patras, Patras, Greece.
authors.forename: Dimitra
authors.initials: D
authors.lastname: Giannakopoulou
authors.affiliation: Department of Biochemistry, School of Medicine, University of Patras, Patras, Greece.
authors.forename: Vassiliki
authors.initials: V
authors.lastname: Stamatopoulou
authors.affiliation: Department of Biochemistry, School of Medicine, University of Patras, Patras, Greece.
authors.forename: Katerina
authors.initials: K
authors.lastname: Grafanaki
authors.affiliation: Department of Anatomy, School of Medicine, University of Patras, Patras, Greece.
authors.forename: Christos G
authors.initials: CG
authors.lastname: Kostopoulos
authors.affiliation: Department of Anatomy, School of Medicine, University of Patras, Patras, Greece.
authors.forename: Helen
authors.initials: H
authors.lastname: Papadaki
authors.affiliation: Laboratory of Biochemistry, Department of Chemistry, School of Natural Sciences, University of Patras, Patras, Greece.
authors.forename: Christina J
authors.initials: CJ
authors.lastname: Malavaki
authors.affiliation: Laboratory of Biochemistry, Department of Chemistry, School of Natural Sciences, University of Patras, Patras, Greece.
authors.forename: Nikos K
authors.initials: NK
authors.lastname: Karamanos
authors.affiliation: Department of Pharmacology, School of Medicine, University of Patras, Patras, Greece.
authors.forename: Stathianna
authors.initials: S
authors.lastname: Douroumi
authors.affiliation: Department of Anatomy, Ηistology and Embryology, School of Medicine, University of Patras, Patras, Greece.
authors.forename: Dionysios
authors.initials: D
authors.lastname: Papachristou
authors.affiliation: Department of Chemistry, School of Natural Sciences, University of Patras, Patras, Greece.
authors.forename: George E
authors.initials: GE
authors.lastname: Magoulas
authors.affiliation: Department of Chemistry, School of Natural Sciences, University of Patras, Patras, Greece.
authors.forename: Dionissios
authors.initials: D
authors.lastname: Papaioannou
authors.affiliation: Department of Biochemistry, School of Medicine, University of Patras, Patras, Greece.
authors.forename: Denis
authors.initials: D
authors.lastname: Drainas
mesh_terms: D000818:Animals; D000831:Animals, Newborn; D000893:Anti-Inflammatory Agents / Q000737:chemistry / Q000633:toxicity*; D001835:Body Weight / Q000187:drug effects; D003433:Crosses, Genetic; D019075:Electrophoresis, Capillary; D005260:Female; D048788:Growth and Development / Q000187:drug effects; D008297:Male; D009929:Organ Size / Q000187:drug effects; D009928:Organ Specificity / Q000187:drug effects; D011073:Polyamines / Q000737:chemistry / Q000633:toxicity*; D017208:Rats, Wistar; D012018:Reflex / Q000187:drug effects; D012176:Retinoids / Q000737:chemistry / Q000633:toxicity*; D013723:Teratogens / Q000633:toxicity*; D018675:Toxicity Tests / Q000379:methods*
chemical_list: D000893:Anti-Inflammatory Agents; D011073:Polyamines; D012176:Retinoids; D013723:Teratogens
keywords: all-trans retinoic acid; anti-inflammatory compound; retinoids; spermine conjugates; teratogenesis