Derangement of hepatic energy metabolism in lead-sensitized endotoxicosis.
Lead-sensitized endotoxicosis was investigated in rats in terms of hepatic energy metabolism. Lead acetate (Ld, 20 mg/kg BW) or endotoxin (Etx, 4 mg/kg BW) caused no deaths within 48 h. Ld plus Etx resulted in a lethality of 50 and 100% within 6 and 12 h respectively. Etx or Ld alone caused a slight but significant decrease in the hepatic tissue levels of total adenine nucleotides and/or ATP at 3 and 6 h after the application. The energy charge potential (ECP) remained normal. The ketone bodies acetoacetate and beta-hydroxybutyrate and the ratio AcAc/beta-OHB as well as the mitochondrial oxidative phosphorylation tended to increase; the hepatic tissue levels of pyruvate and lactate were increased after 3 h, indicative of an accelerated glycolysis. These alterations were no longer detectable after 6 h. In lead-sensitized endotoxemia (Ld + Etx), the total adenine nucleotides and ATP of the liver tissue decreased significantly to 84% (86%) and 71% (52%) of the controls within 3 and 6 h respectively, and the ECP had decreased from 0.865 to 0.684 at 6 h. The ketone bodies were increased, while the ratio AcAc/beta-OHB was significantly decreased at 6 h. The hepatic tissue lactate remained elevated. The mitochondrial activity was significantly reduced. A hyperglycemia (175 mg . dl-1) at 3 h changed into a hypoglycemia (50 mg . dl-1) at 6 h. It is suggested that Ld plus Etx causes a rapid impairment of hepatic mitochondria which leads to a drastic disturbance of the hepatic energy metabolism including hypoglycemia and contributes to an enhanced lethality in Ld-sensitized endotoxicosis.
D000227:Adenine Nucleotides / Q000378:metabolism; D000818:Animals; D001786:Blood Glucose / Q000032:analysis; D004731:Endotoxins / Q000097:blood*; D004734:Energy Metabolism / Q000187:drug effects; D004926:Escherichia coli; D007657:Ketone Bodies / Q000378:metabolism; D007773:Lactates / Q000378:metabolism; D007854:Lead / Q000494:pharmacology*; D008099:Liver / Q000187:drug effects / Q000378:metabolism*; D008297:Male; D008930:Mitochondria, Liver / Q000187:drug effects / Q000378:metabolism; D012157:Mononuclear Phagocyte System / Q000187:drug effects; D009942:Organometallic Compounds; D010085:Oxidative Phosphorylation; D011773:Pyruvates / Q000378:metabolism; D051381:Rats; D011919:Rats, Inbred Strains
D000227:Adenine Nucleotides; D001786:Blood Glucose; D004731:Endotoxins; D007657:Ketone Bodies; D007773:Lactates; D009942:Organometallic Compounds; D011773:Pyruvates; D007854:Lead; C008261:lead acetate