Toxicological effects of Tris (1,3-dichloro-2-propyl) phosphate exposure in adult male rats differ depending on the history of exposure in the neonatal period.

There is increasing concern about multiple high concentration exposure to toxins in disaster and emergency situations. However, conventional toxicology testing methods may not adequately address these situations. Thus, we assessed whether the toxic effects of exposure in the adulthood differ depending on the presence or absence of neonatal exposure to Tris (1,3-dichloro-2-propyl) phosphate (TDCIPP) in male rats to investigate the effects of exposure history of chemicals. In the neonatal stage [postnatal days (PNDs) 1-7], animals were treated with either sesame oil (5 ml/kg/day) as a control or TDCIPP (250 mg/kg/day) dissolved in sesame oil. In adulthood (PND 101-107), animals were treated with either sesame oil (5 ml/kg/day) or TDCIPP (650 mg/kg/day). One day after the final administration, dissection was performed, and body and organ weight, hematology, blood biochemistry, and histopathology were examined. The results demonstrated that the toxic effects of TDCIPP exposure in adulthood on adrenal gland size, serum iron content, and unsaturated iron binding capacity were enhanced by TDCIPP exposure in the neonatal stage. From these findings, it was indicated that the toxic effects of TDCIPP exposure in the adult stage are affected by pediatric exposure. These results suggest that the toxic effects of high-dose and long-term unsteady exposure to chemicals in large-scale disasters may change based on the exposure history of chemicals.

Higher detection sensitivity of anxiolytic effects of diazepam by ledge-free open arm with opaque walled closed arm elevated plus maze in male rats.

The elevated plus maze (EPM) is an established method for testing animal anxiety. However, EPM apparatuses and their features can differ among laboratories, most notably in the presence/absence of ledges on the open arm and/or the transparency/opaqueness of walls on the closed arm. The combined effects of these variable arm features on EPM behavior are not yet fully understood. In the present study, we prepared four types of EPM apparatus - open arms with (0.5 cm) or without (0 cm) ledges×closed arms with transparent or opaque walls - and compared the maze-exploration behavior of male Sprague-Dawley rats. We found that the presence of open arm ledges significantly increased the incidence of open arm exploration. Furthermore, time spent in the distal segment of the open arm was shortest in the apparatus that had open arms with no ledges and opaque closed arms (No-Ledges/Opaque), and was longest in the apparatus that had open arms with ledges and transparent closed arms (Ledges/Transparent). Additionally, the No-Ledges/Opaque apparatus could detect the effect of 0.5mg/kg diazepam, an anxiolytic drug, whereas the Ledges/Transparent apparatus could not. These results indicate that arm structure (features of both open and closed arms) significantly influences maze-exploratory behavior in rats, and that No-Ledges/Opaque apparatuses have higher detection sensitivity for anxiolytic effects of diazepam than that of Ledges/Transparent apparatuses.

Cardiotonic effect of Apocynum venetum L. extracts on isolated guinea pig atrium.

The effects on guinea-pig heart muscle of extracts of Apocynum venetum L. leaf, root, stem, old stem and Venetron--a polyphenol-rich extract of leaves--were studied by recording the mechanical activity and heart rate of isolated right atria. Cymarin--a cardiac glycoside--was also determined in A. venetum extracts by LC-MS/MS analysis. All extracts examined here showed a weak cardiotonic effect, i.e., induced a contractile response of the isolated atria and increased the pulse at a concentration of 1 mg/mL, which was not inhibited by propranolol (1 microM)-a beta-adrenoceptor blocker. The cymarin content in extracts of A. venetum was ranked as follows: old stem >> stem > root > leaf >> Venetron. Since the cardiotonic effects of A. venetum extracts did not reflect the cymarin content, a possible mechanism other than that of cardiac glycosides was investigated. The inhibitory effects on phosphodiesterase 3 (PDE3) were studied in a cell-free enzyme assay; all extracts of various parts of A. venetum inhibited PDE purified from human platelets. These results suggest that PDE3 inhibition may contribute to the cardiotonic effects of A. venetum extracts.