Dose-dependent effects of acute lindane treatment on Kupffer cell function assessed in the isolated perfused rat liver

Abstract

1. Twenty-four hours after lindane exposure (5-60 mg/kg) a dose-dependent increase in the serum and hepatic levels of the insecticide was observed. Both the basal rate of O2 consumption and the sinusoidal efflux of lactate dehydrogenase (LDH) by the perfused rat liver was enhanced after the administration of 20-60 mg lindane/kg. 2. The administration of low doses of lindane (5-20 mg/kg) increased carbon uptake and the carbon-induced O2 consumption by the perfused liver, effects that were abolished by pretreatment with the Kupffer cell inactivator gadolinium chloride (GdCl3). These parameters were not modified at the higher doses of lindane used (40-60 mg/kg). 3. In the dose range of 20-60 mg lindane/kg, carbon infusion led to a further increase in liver LDH efflux over values found in its absence, an effect that was markedly diminished by GdCl3 in rat treated with 20 mg lindane/kg, being unaltered by GdCl3 in animals given 60 mg/kg. 4. It is concluded that lindane induces a dose-dependent biphasic effect on Kupffer cell function, which could be conditioned by differential membrane perturbation actions of the insecticide that progressively accumulates in the liver, thus altering receptor-mediated and enzymatic processes related to colloidal carbon phagocytosis. Increased Kupffer cell function at low doses of lindane leads to enhanced liver injury. However, this feature of lindane intoxication at higher doses (60 mg/kg) is independent of Kupffer cell activity and seems to be determined by an oxidative stress mechanism induced at the parenchymal cell level.