Tolerance to the nephrotoxic component of Narthecium ossifragum in sheep: The effects of repeated oral doses of plant extracts

Young adult sheep were dosed with extracts of Narthecium ossifragum plants by the oral or parenteral routes and the resulting nephrotoxicity was asses sed from the increases in the concentrations of creatinine and urea in the serum. Following single intraruminal or intraperitoneal doses of extracts d erived from 30 g N. ossifragum (wet weight) per kg live weight (kg lw), ser um creatinine concentrations increased from about 100 mu mol/L to between 2 60 and 510 mu mol/L. The serum urea concentrations increased from about 5-8 mmol/L to between 11 and 66 mmol/L in individual sheep. Daily intraruminal administration of 5-30 g/kg lw to three sheep over a 10- or 15-day period increased creatinine concentrations from 100 mu mol/L to 300-760 mu mol/L, and urea concentrations From 5-8 mmol/L to 35 mmol/L. A single intraperiton eal challenge dose of 30 g/kg lw, delivered 7 or 12 days after the final in traruminal dose, did not lead to increased serum creatinine or urea concent rations, indicating that oral treatment had apparently resulted in an incre ased tolerance to the nephrotoxic principle(s) in N. ossifragum.