The effect of phospholipase C in sheep

Area of Science:

• Veterinary Pharmacology
• Toxicology
• Thrombo-embolic Disease Research

Background:

• Phospholipase C (PLC) was previously considered a promising prophylactic for thrombo-embolic disease based on rat studies.
• Recent rabbit studies indicated higher toxicity than anticipated, necessitating further investigation in larger animal models.

Purpose of the Study:

• To evaluate the toxicity of phospholipase C (PLC) in sheep, a larger animal model.
• To determine the lethal dose 50 (LD50) and understand the toxicological mechanisms of PLC in sheep.

Main Methods:

• Administration of varying doses of phospholipase C (PLC) to sheep via infusion and bolus injection.
• Monitoring of physiological parameters, tissue pathology, and plasma enzyme levels in treated and control sheep.
• Estimation of the median lethal dose (LD50) for PLC in sheep.

Main Results:

• The estimated LD50 for PLC in sheep was low, between 0.4 and 0.2 mg/kg for infusion and below 0.2 mg/kg for bolus administration.
• Cellular necrosis was observed in multiple tissues, leading to pulmonary edema, decreased oxygen tension, renal failure (hematuria, proteinuria, glucosuria), and hypoglycemia.
• Elevated plasma enzymes indicated toxic effects on muscle cells and hepatocytes.

Conclusions:

• Phospholipase C (PLC) exhibits significant toxicity in sheep, characterized by widespread cellular necrosis and multi-organ failure.
• Pulmonary edema and renal failure are identified as primary causes of mortality in PLC-treated sheep.
• The findings suggest that PLC's toxicity profile in larger animals like sheep may preclude its use as a prophylactic agent for thrombo-embolic conditions.