This study was designed to confirm the toxicity of a plant implicated in an outbreak in Frankfort, Free State Province, Republic of South Africa. Cows died acutely after being introduced into a camp, where an abundant, green shrublet was noted to be heavily grazed. The plant was subsequently identified as Senecio inaequidens DC. (Asteraceae) by the South African National Biodiversity Institute (SANBI). Extraction and chemical analyses for pyrrolizidine alkaloids (PA's) in Senecio inaequidens revealed the presence of four different compounds, namely retrorsine and senecionine (known to be hepatotoxic) and two unidentified compounds. The total alkaloid content (free bases plus N-oxides) in the dried, milled S. inaequidens plant material was 0.18%. Four (4) male Sprague Dawley rats, aged 8-9 weeks were dosed per os. Each rat received a different dose; ranging from 0.049 mg/g b.w. to 0.25 mg/g b.w.; of the crude Senecio inaequidens extract. No clinical signs were observed in the rat receiving the lowest dose. Rats receiving higher doses showed depression, an unsteady gait, pilo-erection and jaundice, which was particularly noticeable in the ears. Clinical chemistry evaluation revealed an increase in the activities of ALP, AST (except Rat 1) and GGT in all animals. Total serum bilirubin, creatinine and urea concentrations were also elevated. All rats had low serum globulin concentrations with an A/G ratio above 1.88 (except Rat 1). Post mortem examination of the rats revealed marked hepatic lesions. Histopathological changes were characterized by necrosis (variable in extent) of the centrilobular and midzonal hepatocytes, sparing the portal hepatocytes, with extensive haemorrhage and congestion. Proliferation of the bile ducts, fibrosis and oedema was also present. Ultrastructural changes in affected rats were characterized by margination of chromatin, the presence of numerous autolysosomes in necrotic hepatocytes, intramitochondrial woolly inclusions and changes in the endoplasmic reticulum. A sheep was also dosed in an attempt to reproduce the intoxication. The sheep did not exhibit clinical signs, clinical chemistry aberrations or macroscopic lesions. Histopathological and ultrastructural changes, although milder, were similar to those displayed by the rats. Pyrrolizidine alkaloids were extracted from the liver and kidneys of the rats and sheep. Retrorsine was also detected in the lungs, urine and bile of the sheep.
Dissertation (MSc (Paraclinical Science))--University of Pretoria, 2008.