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Cypermethrin increases apo A-1 and apo B mRNA but not hyperlipidemia in rats
L Aldana1, E González de Mejía, A Craigmill
1Universidad Autónoma de Querétaro, Mexico.
Abstract:
The hepatotoxic effect of cypermethrin and the expression of hepatic genes at the mRNA level, as molecular markers of liver damage, were evaluated in rats following exposure to cypermethrin. The expression of hepatic genes was compared with conventional liver functional tests, and correlations were made by studying the liver at the ultrastructural level. Cypermethrin treated rats presented a significant decrease, of 79% and 22%, on the expression of albumin and apo E genes at 5 days, respectively. The levels of apo A-1 and apo B mRNA were increased up to four- and fivefold, respectively. This increase did not correlate with the serum values of HDL and VLDL lipoprotein particles. Intracytoplasmic lipid droplets were observed after the first 2 days following cypermethrin administration, suggesting that apo A-1 and B mRNA were translated but not secreted. There were significant correlations between the low values of the albumin gene expression, the decrease in the HDL concentrations, and the ultrastructural alterations, respectively. These alterations were mainly a large amount and increased size of mitochondria in the animals exposed to cypermethrin. It is concluded that under the experimental conditions used, cypermethrin may alter the metabolism of lipids and proteins in rat liver.
Insights
Cypermethrin exposure in rats significantly altered liver gene expression, impacting albumin and apo E. This suggests cypermethrin disrupts lipid and protein metabolism, leading to liver damage.
Area of Science:
- Toxicology
- Molecular Biology
- Hepatology
Background:
- Cypermethrin is a widely used insecticide.
- Hepatotoxicity is a potential adverse effect of pesticide exposure.
- Gene expression analysis offers sensitive molecular markers for liver injury.
Purpose of the Study:
- To evaluate the hepatotoxic effects of cypermethrin in rats.
- To assess changes in hepatic gene expression (mRNA levels) as indicators of liver damage.
- To correlate molecular markers with conventional liver function tests and ultrastructural changes.
Main Methods:
- Rats were exposed to cypermethrin.
- Hepatic gene expression for albumin, apo E, apo A-1, and apo B was quantified at the mRNA level.
- Conventional liver function tests were performed.
- Liver ultrastructure was examined using electron microscopy.
Main Results:
- Cypermethrin exposure significantly decreased albumin (79%) and apo E (22%) gene expression at 5 days.
- Apo A-1 and apo B mRNA levels increased four- and fivefold, respectively, but did not correlate with serum lipoprotein levels.
- Intracytoplasmic lipid droplets were observed, suggesting impaired protein secretion.
- Significant correlations were found between decreased albumin expression, reduced HDL, and ultrastructural alterations, including mitochondrial changes.
Conclusions:
- Cypermethrin exposure alters lipid and protein metabolism in the rat liver.
- Changes in gene expression, particularly for albumin, correlate with functional and structural liver damage.
- Mitochondrial alterations are a key ultrastructural finding in cypermethrin-induced hepatotoxicity.