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Decrease in hepatic microsomal UDP-glucuronosyl-transferase activity in rats and cattle with fascioliasis: impaired
Toxicology Letters
|July 1, 1985
Summary
Liver fluke infection significantly reduces hepatic microsomal UDP-glucuronosyl-transferase activity in rats and cattle. This enzyme decrease may explain toxic episodes during chemotherapy with oxyclozanide due to impaired drug metabolism.
Area of Science:
- Veterinary Medicine
- Parasitology
- Biochemistry
Background:
- Liver fluke (Fasciola hepatica) infections are common in livestock.
- Parasitic infections can alter host metabolism.
- Intensive chemotherapy with drugs like oxyclozanide is used to treat fascioliasis.
Purpose of the Study:
- To investigate the impact of Fasciola hepatica infection on hepatic microsomal UDP-glucuronosyl-transferase (UGT) activity.
- To determine if altered UGT activity explains toxic episodes in animals treated with oxyclozanide.
Main Methods:
- Studied UGT activity in liver microsomes from experimentally infected rats and naturally infected cattle.
- Assessed UGT activity using p-nitrophenol as a substrate.
- Evaluated in vitro glucuronic acid conjugation of oxyclozanide by microsomes from infected cattle.
Main Results:
- Observed dramatic decreases in UGT activity in both infected rats and cattle, even with minimal liver lesions.
- Demonstrated a similar loss of oxyclozanide glucuronidation in vitro by microsomes from infected cattle.
- Hypothesized that reduced UGT activity leads to slower drug elimination and accumulation in vivo.
Conclusions:
- Fasciola hepatica infection significantly impairs hepatic microsomal UGT activity.
- Reduced UGT activity is a likely mechanism contributing to oxyclozanide toxicity in infected animals.
- Findings highlight the importance of considering host-parasite interactions in drug efficacy and safety.