Influence of oral application of mycophenolic acid on the clinical health status of sheep.

Mycophenolic acid (MPA) is an immunosuppressive metabolite of various fungi, especially of Penicillium roqueforti, and can be found in considerable amounts in mouldy silage. The aim of this study was to investigate the effect of MPA on sheep. Thirty-six castrated male sheep aged 7 +/- 1 months were randomly divided into four groups of nine sheep. Different dosages of MPA were administered orally to all groups (group 1/2/3/4: 0/10/70/300 mg MPA/animal daily) for a period of 44 days. Throughout the trial, the sheep were examined daily. Jugular vein blood was taken twice weekly to analyse haematological and biochemical parameters. No significant influence was observed on the number of erythrocytes, thrombocytes, leucocytes (including differentiation), packed cell volume, haemoglobin-, glucose- and bilirubin-concentration, activity of alanine amino transferase, aspartate amino transferase and glutamate dehydrogenase. Even an oral application of up to 300 mg MPA/animal daily, which is equivalent to 5.4 mg/kg body weight, did not affect the sheep's general state of health and weight gain significantly. Mycophenolic acid and its glucuronide were analysed in plasma samples of groups treatments from day 1 on with mean concentrations up to 0.29 +/- 0.13 microg/ml (MPA) and 11.0 +/- 2.9 microg/ml (MPA glucuronide) respectively (group 4). There were no indications for a ruminal reduction of MPA. The postmortem dissection revealed minor alterations in lung, spleen, liver and kidneys, unrelated to the MPA dosage. The results of the study indicate that MPA concentrations occurring naturally in silage have no obvious impact on sheep health.