Increase of serum very low density lipoproteins in rats after administration of ?-hexachlorocyclohexane

Abstract

After enteral administration of 200 mg/kg alpha-hexachlorocyclohexane (alpha-HCH) female Wistar rats develop a hyperlipemia. 48 h after administration of alpha-HCH, serum triglycerides are increased by 300%, whereas both serum cholesterol and serum total phospholipids only increase by about 45%. Serum free fatty acids are not significantly altered. Fractionation of the serum lipoproteins by ultracentrifugation shows that the hyperlipemia is due to a fivefold increase in serum very low density lipoproteins. Hepatic triglyceride secretion, calculated after i.v. injection of Triton WR 1339, is increased in animals pretreated wtih alpha-HCH. Corresponding to this observation, drugs known to diminish the triglyceride secretion of the liver, such as actinomycin D, cycloheximide; glucagon, orotic acid, CFT 1201, and CFT 1042 reduce the alpha-HCH-induced hyperlipemia. We concluded from the results that hyperlipoproteinemia after alpha-HCH is due to an increased hepatic very low density lipoprotein secretion. At the same time, the blood sugar level was decreased in fasting animals after treatment with alpha-HCH. Earlier experiments suggest that this effect is due to a decreased gluconeogenesis in the liver.

Gene Expression Profiles in Rat Liver Slices Exposed to Hepatocarcinogenic Enzyme Inducers, Peroxisome Proliferators, and 17α-Ethinylestradiol

“…Furthermore, within the family of membrane proteins, the expression of low-density lipoprotein receptor (LDL receptor) was reduced in α - HCH–treated rat liver slices. This is in keeping with findings that female Wistar rats that had been given α -HCH develop a hyperlipemia, due to an increase in serum very-low-density lipoprotein (Grajewski and Oberdisse 1977). Regarding signal transduction, the expression of both of the mitogen-activated protein (MAP) kinase family members ERK2 and ERK3 was changed, ERK3 being increased and ERK2 repressed.…”

A Comparative Study of Gene Expression Profiles in Rat Liver After Administration of Alpha-Hexachlorocyclohexane and Lindane

“…Grajewski et al reported that female Wistar rats developed hyperlipemia after enteral administration of 200 mg/kg alpha-HCH and serum triglycerides were increased by 300% at 48 h after administration, with increased hepatic very low density lipoptotein (VLDL) secretion (Grajewski and Oberdisse, 1977). Both serum cholesterol and serum total phospholipids were also increased by about 45%, whereas serum free fatty acids were not significantly altered.…”

Genomic analysis of metabolic pathway gene expression in mice

“…In the bile acid pathway, cholesterol serves as a substrate that is converted to bile acids through the activation of 7-α-hydroxylase, the transcript for which is also significantly elevated in obese mice. Lastly, studies show that γ-hexachlorocyclohexane administration has been shown to increase serum cholesterol and very low-density lipoprotein (VLDL) levels [24]. Several genes occur multiple times in these 13 pathways (for example, the aldehyde dehydrogenase gene family ( Aldh1a1 , Aldh2 , and Aldh3a2 )).…”