Effect of prior sporidesmin intoxication on the pancreopathy associated with zinc oxide toxicity

Aim. To demonstrate the effect of prior sporidesmin-induced liver injury on the pancreopathy of zinc-induced toxicity. Methods. Four groups, each of 15 sheep, were given 2 x 2 treatments of spor idesmin (0.3 mg/kg bodyweight spread over 3 consecutive days prior to zinc) and zinc (200 mg Zn/kg bodyweight as ZnO spread over 24 days) starting 4 d ays after the end of sporidesmin dosing. Liver and pancreatic changes were assessed by serum enzyme changes (serum amylase and gamma glutamyltransfera se) or scoring for injury at post-mortem examination (hepatopathy) or by hi stopathological examination (pancreopathy). Results. Minor pancreatic injury was caused by the administration of zinc. The pancreopathy associated with zinc oxide toxicity was significantly grea ter in those sheep receiving zinc after the sporidesmin-induced injury. Pat hological and body weight changes associated with sporidesmin toxicity also occurred in both groups dosed with sporidesmin. These were slightly less i n the group of sheep receiving zinc after the sporidesmin challenge than in those receiving sporidesmin alone. Conclusions. Zinc-induced pancreatic injury is greater if the zinc is admin istered after liver injury has been caused by sporidesmin. Only minor prote ction is given by zinc if it is administered after the challenge with spori desmin. Clinical significance. The safety margin for the use of zinc is red uced if zinc is administered after significant liver injury has been caused by prior exposure to high Pithomyces chartarum spore counts.