The role of dietary isoflavones in the reproductive and hepatic systems of domestic and non-domestic feline species : a thesis presented in partial fulfilment of the requirements for the degree of Doctor of Philosophy, Nutritional Science, at Massey University, Palmerston North, New Zealand

Abstract

Dietary isoflavones are thought to influence reproductive and hepatic parameters in captive cheetahs. The isoflavone content of commercially-available feline diets was evaluated and isoflavones were found to be common constituents of diets consumed by captive cheetahs and domestic cats (occurring in over 75% of both diet types). Exposure of domestic cats was estimated to range between 0 and 8 mg/kg BW total isoflavones, whilst captive cheetah exposure was ranged from 0 to 4 mg/kg BW. Single oral bolus doses of isoflavones were administered to captive cheetahs (n = 4) and domestic cats (n = 18) and serial blood, urine and faecal samples collected and analysed for isoflavone metabolite content. The fraction of isoflavone absorbed, as estimated from the plasma concentration over time, was 54% for genistein and 29% for daidzein in domestic cats. However cheetahs absorbed significantly less of both isoflavones (33% for genistein and 11% for daidzein). Sulphate conjugates predominanted the plasma metabolite profile (90% of plasma metabolites) in both species, but cheetah plasma contained approximately twice the amount of unbound genistein and daidzein than cats (as a fraction of the total detected). A dose- and/or diet-related response was observed in domestic cat studies but further testing is required to confirm this. Prior exposure to an isoflavone-containing diet appeared to enhance the production of equol, a metabolite of daidzein. The cheetah appears to be less efficient in its absorption of isoflavones, although this species is potentially inferior in its conjugation capacity. A positive correlation was observed between cheetah age and the proportion of absorbed fraction appearing as a conjugate in the plasma of this species. Vaginal cytology was monitored in domestic cats consuming the purified isoflavones gcnistein and daidzein from weaning until 480 days of age and compared to that of unexposed, related cats. The reproductive tract from each cat was then removed during routine gonadectomy and a liver biopsy collected for comparison between groups. No difference in wet weight of reproductive tracts was detected. However, luminal epithelial cell height was greater in tissues from isoflavone-treated cats (p < 0.05). No differences were found in follicle development or distribution between groups and no histological abnormalities were detected. Expression of Oestrogen Receptor α and β was up-regulated in treatment cat tissues, while Progesterone Receptor expression was down-regulated, compared to control tissues (p < 0.05). Hepatic histology and the extent of fibrosis was unremarkable in both groups. These findings indicate that despite their poor absorption and efficient conjugation, isoflavones consumed at doses representative of commercially-available diets are still capable of exerting biological activity in the reproductive tract of domestic cats. However no influence was detectable in the liver parameters measured. The potentially lower conjugation capacity of the cheetah may confer divergent biological activity in this species.