Derangement of Hepatic Energy Metabolism in Lead-Sensitized Endotoxicosis

Abstract

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 β-hydroxybutyrate and the ratio AcAc/β-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/β-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.

Pretreatment Hepatoprotective Effect of the Marine Fungus Derived from Sponge on Hepatic Toxicity Induced by Heavy Metals in Rats

“…As seen in Figure 7(b), on the other hand, lead overloads stimulated oxidative damage in the liver tissue by causing oxidation of lipid. These enzymes cause liver injury [118]; this was confirmed in this study by the histopatholgical result of liver tissue induced by the heavy metal mixture alone (group II) as seen in Figures 7(a)–7(h). …”

Susceptibility of Overweight Mice to Liver Injury as a Result of the ZnO Nanoparticle-Enhanced Liver Deposition of Pb2+

“…Pb 2+ causes oxidative damage in liver tissues by enhancing lipid peroxidation in the cell membranes 44,45 and inhibiting the activity of antioxidants, 46 which result in the derangement of hepatic biochemical pathways and energy metabolism. 47 These toxic effects depend on the dosage and exposure time of the Pb 2+ treatment. Furthermore, Pb 2+ enhances LPS-induced liver injury, which suggests that it has a pro-inflammatory effect.…”

Combined efficacies of lipoic acid and 2,3-dimercaptosuccinic acid against lead-induced lipid peroxidation in rat liver

“…Reports on lead-induced oxidative stress dates back to 1965 [10]. Lead can cause derangement of several hepatic biochemical pathways and energy metabolism [11]. In particular lead causes transient, but marked hypercalaemia, which may contribute to hepatotoxicity [12].…”