Mesenchymal Wt1 positive stellate cells represent a minor source of the fibrotic response in pancreatitis

Seeds of Crotalaria retusa containing 6.84% (dry weight) of monocrotaline (MCT) were administered experimentally to sheep. Three sheep that received 136.8 mg MCT/kg bw daily for 70 days had no clinical signs. Five out of six sheep ingesting single doses of 205.2 and 273.6 mg MCT/kg bw died with acute (three sheep) or chronic intoxication (two sheep). Acute intoxicated sheep had periacinar liver necrosis and chronic intoxicated sheep liver fibrosis and megalocytosis. Another three sheep had no clinical signs after the ingestion of 20 daily doses of 136.8 mg MCT/kg, followed by seven doses of 273.6 mg MCT/kg, and one single dose of 342 mg MCT/kg. These experiments demonstrated that sheep are susceptible to acute intoxication by MCT being intoxicated by a single oral dose of approximately 205.2 mg/kg. In contrast, they develop strong resistance to MCT after the daily ingestion of non lethal doses (136.8 mg/kg). It is suggested that chronic poisoning does not occur by the repeated ingestion of non acutely toxic doses, but probably by the ingestion of single toxic doses. It is also suggested that sheep do not become intoxicated with the ingestion of C. retusa in the vegetative non-seeding stage.