Abstract
Groups of six normal +/Y and six spf/Y mice with X-linked ornithine transcarbamylase (OTC) deficiency were given SV in drinking water in increasing concentrations of 0, 0.05, 0.15 and 0.25 % for 3 days each. Two out of six spf/Y mice became symptomatic at low intakes (34-85 mg/kg/d). One of these died and the other was sacrificed. Its plasma NH3 was 440 μM as compared to 255 ± 42 in other spf/Y. Four spf/Y and all +/Y survived the treatment (intake: 612-715 mg/kg/d). SV intake was similar in surviving animals. There were no significant changes in orotate excretion; α-amino N increased progressively. Liver carbamyl phosphate synthetase (CPS-I) increased significantly in treated mice, while no changes were seen in OTC activity.Severely affected spf/Y mice showed centrilobular necrosis with cytoplasmic vacuolization and microvesicular steatosis, indicating an idiosyncratic/hepatotoxic response. All other treatted mice showed random single cell necrosis. On electron microscopy, the severely affected spf/Y had swollen mitochondria, dilated RER and glycogen depletion. The results indicate the existence of a susceptible sub-population in spf/Y mice which develops SV toxlcity at low doses, and can be differentiated from other spf/Y mice by a different histopathologic response.(* Present address: Sandoz Ltd., CH-4002, Basel, Switzerland) (Research sponsored by the Canadian Liver Foundation)
Talk to us
Join us for a 30 min session where you can share your feedback and ask us any queries you have
Schedule a callDisclaimer: All third-party content on this website/platform is and will remain the property of their respective owners and is provided on "as is" basis without any warranties, express or implied. Use of third-party content does not indicate any affiliation, sponsorship with or endorsement by them. Any references to third-party content is to identify the corresponding services and shall be considered fair use under The CopyrightLaw.
