Sporidesmin toxicity in rabbits: biochemical and morphological changes

Area of Science:

• Veterinary Pathology
• Toxicology
• Comparative Medicine

Background:

• Sporidesmin toxicity is a significant concern in ruminants, leading to facial eczema.
• Understanding the mechanisms of sporidesmin-induced hepatobiliary damage is crucial for developing preventative strategies.

Purpose of the Study:

• To characterize the sequential hepatobiliary lesions induced by oral sporidesmin administration in rabbits.
• To evaluate serum biochemical markers as indicators of sporidesmin toxicity in rabbits.
• To assess the suitability of the rabbit as an animal model for studying sporidesmin-induced liver disease.

Main Methods:

• Rabbits were orally dosed with sporidesmin (2 mg/kg body weight).
• Histopathological examination of liver and gallbladder tissues was performed at various time points post-dosing.
• Serum biochemical parameters including cholesterol, total bilirubin, Gamma-glutamyl transferase (GGT), and ID activity were measured.

Main Results:

• The earliest lesion observed was hepatocyte necrosis, followed by severe necrotizing cholangitis affecting intrahepatic and extrahepatic bile ducts and the gallbladder.
• Progressive fibrosis and bile ductule proliferation led to pseudo-lobulation by day 21.
• Hepatic necrosis was associated with vascular necrosis and thrombosis adjacent to damaged bile ducts.
• Serum GGT and bilirubin levels correlated with biliary lesion severity, while ID activity was a key indicator of hepatic necrosis.

Conclusions:

• Oral sporidesmin induces significant, dose-dependent hepatobiliary lesions in rabbits, mirroring those seen in ruminants.
• The rabbit model demonstrates a clear correlation between serum markers and the extent of liver damage.
• Rabbits are a suitable and valuable model for investigating the pathogenesis and potential treatments for sporidesmin toxicity, including facial eczema in sheep.