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 assessed from the increases in the concentrations of creatinine and urea in the serum. Following single intraruminal or intraperitoneal doses of extracts derived from 30 g N. ossifragum (wet weight) per kg live weight (kg lw), serum creatinine concentrations increased from about 100 micromol/L to between 260 and 510 micromol/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 micromol/L to 300-760 micromol/L, and urea concentrations from 5-8 mmol/L to 35 mmol/L. A single intraperitoneal challenge dose of 30 g/kg lw, delivered 7 or 12 days after the final intraruminal dose, did not lead to increased serum creatinine or urea concentrations, indicating that oral treatment had apparently resulted in an increased tolerance to the nephrotoxic principle(s) in N. ossifragum.