Dedicated to


ABSTRACT

Male Wistar rats were pretreated with six cyclic monoterpenes, i.e. (+)limonene, (-)limonene, menthol, limonene oxide, alpha-terpineol and terpinene-4-ol by gastric intubation at a dose level of 1.5g/kg body weight per day for 3 days. Menthol, limonene oxide and alpha-terpineol increased the activity of pentoxyresorufin O-depentylase which is an indication of cytochrome P450IIB1 induction. Alpha-terpineol also had a profound effect on cyanide-insensitive palmitoyl-CoA oxidation but with no effect on lauric acid hydroxylation, which implies that it causes peroxisomal proliferation without inducing cytochrome P450IVA1. Terpinene-4-ol killed all the rats before the end of the dosing period, indicating that its LD50 is outside the range of the group LD50's for monoterpenes. An inverse correlation was observed between the effect of the compounds on cytochrome P450IIB1 and P450IIE.


ACKNOWLEDGEMENTS

I am taking this opportunity to thank Dr. R. Jones, the Director of Postgraduate studies for selecting and nominating me for the Caledonian scholarship and his untiring urge to offer assistance and advice where needed, and the trustees of the Caledonian Research Fund for their generosity in funding me on the MSc Toxicology programme. I particularly enjoy paying visits to my course organiser Dr. S. Bennett, for her friendliness, openmindedness and keenness to offer advice and listen to comments on various aspects of the course.

I am grateful to the following: my project supervisors, Professor R. Walker and Dr. C. Ioannides for their direction and supervision of the project and particularly Dr. C. Ioannides for his close and frequent scrutiny of results, recommendation on protocols, analysis and presentation of results, Mrs Judith Wilson for her introductory exercises on the enzyme assays, Dr. O. Ayalogu for his instruction and assistance in preparation of the microsomes, enzyme assays and general comment on procedures and my partner Miss Margaret Ebling, for her co-operation and dedication. The assays for my last compound alpha-terpineol was done by Miss Ebling with collaboration from Dr. Ayalogu due to my inability to carry on with the assays after incuring a fracture of the left fibular.

I am grateful to all those who have expressed their sympathy in one form or the other: Mr Safraz Ahmed, Assistant Warden for Guildford Court and PhD student in aerodynamics for helping me with my daily chores, I would not have been able to cope without his assistance; Dr. Ayalogu, Dr. Nana Yeboah, Miss Amaia Irizar, Miss Ebling and Mrs Valerie Asmah for their frequent visits; Mrs Judith Wilson and Miss Yunshin Hwang for making trips to Hospital with me and last but not least Mr Steve Russel, who rushed to town in search for ink for my printer on Monday morning so that I could meet the deadline set for the project to be handed in.