Depletion of hepatic coenzyme A derivatives is one of the markers of the toxicity of orally administered secondary autoxidation products of linoleic acid in rat.
When 400 mg/rat/day of secondary autoxidation products of linoleic acid was orally administered 3 times to rats, they died at 30-40 h after the third dose. To search the markers of the toxicity of secondary products in vivo, the rats were killed at 24h after the third dose, and conditions of their digestive tracts and liver were analyzed. In the stomach, macroscopically, inflation, retention of undigested food, and edema were seen. Slight congestions were detected in the small intestines. It was considered that these injuries led to reduction in food consumption and then depression of the growth, but did not lead to the death of the animals. The lipid peroxide levels in the liver and the activities of its detoxifying enzymes were increased as compared to those in the control groups. The hepatic lipid contents and unsaturated fatty acid compositions were also not changed. The endogenous lipid peroxidation, therefore, did not give the rats a severe stress. The activities of hepatic acetyl-CoA carboxylase and carnitine palmitoyltransferase were 20 and 35% lower than those of control, respectively. The levels of CoASH, acetyl-CoA, and long-chain acyl-CoA were 1/9, 1/2, and 1/4 of those in control, respectively. Thus, one of the markers of the toxicity of secondary products was the depletion of hepatic CoA derivatives. In rat, bio-energy was reduced by the decrease in the intestinal absorption of nutrients, and the depletion of hepatic CoA derivatives also failed to supply energy with beta-oxidation.
Kanazawa
K
K
Department of Agricultural Chemistry, Kobe University, Hyogo, Japan.
Ashida
H
H
Mizuno
M
M
Natake
M
M
D000818:Animals; D001835:Body Weight / Q000187:drug effects; D003065:Coenzyme A / Q000172:deficiency*; D004064:Digestive System / Q000187:drug effects; D008041:Linoleic Acids / Q000008:administration & dosage / Q000378:metabolism / Q000633:toxicity*; D008054:Lipid Peroxides / Q000032:analysis; D008099:Liver / Q000187:drug effects / Q000378:metabolism*; D008297:Male; D009929:Organ Size / Q000187:drug effects; D010084:Oxidation-Reduction; D051381:Rats; D011919:Rats, Inbred Strains; D014810:Vitamin E / Q000097:blood
D008041:Linoleic Acids; D008054:Lipid Peroxides; D014810:Vitamin E; D003065:Coenzyme A