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Biliary hyperplasia and carcinogenesis in chronic liver damage induced in rats by phomopsin
1CSIRO Division of Animal Health, Animal Health Research Laboratory, Parkville, Victoria.
Abstract:
Phomopsin, a hexapeptide mycotoxin contaminant of lupin plant and seed materials, was administered subcutaneously to adult rats at a daily dose rate of 30 micrograms/kg body weight (approximately 0.005 median lethal dose) for 2, 6 or 17 wks and the development of liver damage was observed during treatment and for up to 2 yr after. All rats injected for 17 wks developed permanent liver damage characterized by nodular cirrhosis and extensive biliary hyperplasia. Cholangiomas developed in 60% of these rats and cholangiocarcinomas and hepatocellular carcinomas in 13%. Similar effects were produced in some rats injected for 6 wks, while in others the cessation of treatment was followed by almost complete regression of the liver lesions. Livers damaged by 2 wks of injection had fully recovered within a few wks. The permanence of the liver damage is relevant to the management of stock exposed seasonally to the toxin, while its carcinogenic potential in rats, although not high, indicates the need for monitoring of the phomopsin content of lupin seed or flour prepared for human consumption.
Insights
Phomopsin mycotoxin in lupins causes permanent liver damage and cancer in rats with prolonged exposure. Shorter exposure may lead to reversible liver damage, highlighting the need for monitoring lupin products.
Area of Science:
- Toxicology
- Hepatology
- Carcinogenesis
Background:
- Phomopsin is a hexapeptide mycotoxin found in lupin plants and seeds.
- Mycotoxin contamination poses risks to animal and human health through food sources.
Purpose of the Study:
- To investigate the long-term effects of phomopsin administration on rat liver.
- To determine the dose-response relationship and reversibility of phomopsin-induced liver damage.
- To assess the carcinogenic potential of phomopsin in a rodent model.
Main Methods:
- Adult rats were subcutaneously injected with phomopsin (30 µg/kg/day) for 2, 6, or 17 weeks.
- Liver damage was monitored during treatment and for up to 2 years post-exposure.
- Histopathological analysis was performed to characterize liver lesions and tumors.
Main Results:
- 17-week exposure resulted in permanent nodular cirrhosis, biliary hyperplasia, and a high incidence of cholangiomas, cholangiocarcinomas, and hepatocellular carcinomas.
- 6-week exposure caused similar, but less severe, effects, with some cases showing lesion regression after treatment cessation.
- 2-week exposure led to transient liver damage that fully recovered post-treatment.
Conclusions:
- Prolonged phomopsin exposure induces permanent, potentially carcinogenic liver damage in rats.
- The duration of exposure is critical in determining the severity and permanence of phomopsin-induced hepatotoxicity.
- Monitoring phomopsin levels in lupin-based food products is crucial for human and animal safety.